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  • 1.
    Adbo, Karina
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Håkan S.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Ankarloo, Jonas
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Karlsson, Jesper G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Norell, M C
    Olofsson, Linus
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Svenson, Johan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Örtegren, U
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Enantioselective synthetic receptors for Tröger’s base1999In: Bioorganic Chemistry, Vol. 27, no 5, p. 363-371Article in journal (Refereed)
  • 2.
    Andersson, Håkan S.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Karlsson, Jesper G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Piletsky, S A
    Koch-Schmidt, Ann-Christin
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Mosbach, K
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Influence of monomer-template ratio on selectivity and load capacity of molecularly imprinted polymers: indications of template self-association1999In: Journal of Chromatography A, Vol. 848, no 1-2, p. 39-49Article in journal (Refereed)
  • 3.
    Andersson, Håkan S.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Karlsson, Jesper G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Svenson, Johan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Can template-template self-association contribute to polymer-ligand recognition characteristics?2000Conference paper (Refereed)
  • 4.
    Andersson, Håkan S.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular Imprinting. Recent innovations in synthetic polymer receptor and enzyme mimics1997In: Recent Research Developments in Pure and Applied Chemistry, Vol. 1, p. 133-157Article in journal (Refereed)
  • 5.
    Andersson, Håkan S.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Spectroscopic evaluation of molecular imprinting polymerization systems1997In: Bioorganic Chemistry, Vol. 25, p. 203-211Article in journal (Refereed)
  • 6.
    Andersson, Håkan S.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    The development of molecular imprinting2000Other (Other academic)
  • 7.
    Andersson, Håkan S.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Piletsky, S A
    Mosbach, K
    Koch-Schmidt, Ann-Christin
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Novel recognition elements for improved molecularly imprinted polymer stereoselectivity1997Conference paper (Refereed)
  • 8.
    Ankarloo, Jonas
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wikman, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Escherichia coli mar and acrAB Mutants Display No Tolerance to Simple Alcohols2010In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 11, no 4, p. 1403-1412Article in journal (Refereed)
    Abstract [en]

    The inducible Mar phenotype of Escherichia coli is associated with increased tolerance to multiple hydrophobic antibiotics as well as some highly hydrophobic organic solvents such as cyclohexane, mediated mainly through the AcrAB/TolC efflux system. The influence of water miscible alcohols ethanol and 1-propanol on a Mar constitutive mutant and a mar deletion mutant of E. coli K-12, as well as the corresponding strains carrying the additional acrAB deletion, was investigated. In contrast to hydrophobic solvents, all strains were killed in exponential phase by 1-propanol and ethanol at rates comparable to the parent strain. Thus, the Mar phenotype does not protect E. coli from killing by these more polar solvents. Surprisingly, AcrAB does not contribute to an increased alcohol tolerance. In addition, sodium salicylate, at concentrations known to induce the mar operon, was unable to increase 1-propanol or ethanol tolerance. Rather, the toxicity of both solvents was increased in the presence of sodium salicylate. Collectively, the results imply that the resilience of E. coli to water miscible alcohols, in contrast to more hydrophobic solvents, does not depend upon the AcrAB/TolC efflux system, and suggests a lower limit for substrate molecular size and functionality. Implications for the application of microbiological systems in environments containing high contents of water miscible organic solvents, e. g., phage display screening, are discussed.

  • 9.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Suriyanarayanan, Subramanian
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Aastrup, Teodor
    Attana AB.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Biotin selective polymer nano-films2014In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 12, article id 8Article in journal (Refereed)
    Abstract [en]

    Background: The interaction between biotin and avidin is utilized in a wide range of assay and diagnostic systems. A robust material capable of binding biotin should offer scope in the development of reusable assay materials and biosensor recognition elements. Results: Biotin-selective thin (3-5 nm) films have been fabricated on hexadecanethiol self assembled monolayer (SAM) coated Au/quartz resonators. The films were prepared based upon a molecular imprinting strategy where N, N'-methylenebisacrylamide and 2-acrylamido-2-methylpropanesulfonic acid were copolymerized and grafted to the SAM-coated surface in the presence of biotin methyl ester using photoinitiation with physisorbed benzophenone. The biotinyl moiety selectivity of the resonators efficiently differentiated biotinylated peptidic or carbohydrate structures from their native counterparts. Conclusions: Molecularly imprinted ultra thin films can be used for the selective recognition of biotinylated structures in a quartz crystal microbalance sensing platform. These films are stable for periods of at least a month. This strategy should prove of interest for use in other sensing and assay systems.

  • 10.
    Giovannoli, Cristina
    et al.
    Univ Turin, Italy.
    Passini, Cinzia
    Univ Turin, Italy.
    Di Nardo, Fabio
    Univ Turin, Italy.
    Anfossi, Laura
    Univ Turin, Italy.
    Baggiani, Claudio
    Univ Turin, Italy.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Affinity Capillary Electrochromatography of Molecularly Imprinted Thin Layers Grafted onto Silica Capillaries Using a Surface-Bound Azo-Initiator and Living Polymerization2018In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 10, no 2, article id 192Article in journal (Refereed)
    Abstract [en]

    Molecularly imprinted thin layers were prepared in silica capillaries by using two different surface polymerization strategies, the first using 4,4-azobis(4-cyanovaleric acid) as a surface-coupled radical initiator, and the second, S-carboxypropyl-S'-benzyltrithiocarbonate as a reversible addition-fragmentation chain transfer (RAFT) agent in combination with 2,2-azobisisobutyronitrile as a free radical initiator. The ability to generate imprinted thin layers was tested on two different polymerization systems: (i) a 4-vinylpyridine/ethylene dimethacrylate (4VP-EDMA) in methanol-water solution with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) as a template; and (ii) methacrylic acid/ethylene dimethacrylate (MAA-EDMA) in a chloroform solution with warfarin as the template molecule. The binding properties of the imprinted capillaries were studied and compared with those of the corresponding non-imprinted polymer coated capillaries by injecting the template molecule and by measuring its migration times relative to a neutral and non-retained marker. The role of running buffer hydrophobicity on recognition was investigated by studying the influence of varying buffer acetonitrile concentration. The 2,4,5-T-imprinted capillary showed molecular recognition based on a reversed phase mechanism, with a decrease of the template recognition in the presence of higher acetonitrile content; whereas warfarin-imprinted capillaries showed a bell-shaped trend upon varying the acetonitrile percentage, illustrating different mechanisms underlying imprinted polymer-ligand recognition. Importantly, the results demonstrated the validity of affinity capillary electrochromatography (CEC) to screen the binding properties of imprinted layers.

  • 11.
    Golker, Kerstin
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Towards Molecular Dynamics-Based Rational Design of Polymeric Recognition Systems2010Conference paper (Refereed)
    Abstract [en]

    Molecular imprinting is a technique used to design polymeric recognition materials with selectivity for a predetermined structure. The molecular imprinting process generates cavities in the polymer matrix that are complementary in size, shape and functionality to the template-structure. The recognition properties of molecularly imprinted polymers (MIPs) are comparable to those of antibodies and enzymes, which make MIPs utilizable in a wide range of application areas including biomimetic assays and biosensors [1]. Previous studies have shown that the prepolymerization step is central for the establishment of high affinity binding sites in MIPs [2]. However, our understanding of the physical mechanisms underlying MIP formation and template recognition is still limited. With the rapid increase of computational power and the development of suitable software molecular dynamics (MD) simulation methods have become a valuable theoretical tool to aid our understanding of the molecular imprinting process, and even in the development of rational design strategies [2]. Recently the first simulation of a complete prepolymerization mixture was presented [3].

    Here we present 10 ns MD simulations of a series of all-component prepolymerization mixtures. The simulated systems were assembled with different molar ratios using the local anaesthetic bupivacaine as the template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinker, 2,2’-azobis-(2-methylpropionitrile) (AIBN) as the initiator and toluene as the solvent. The simulations were performed using the AMBER (v. 10.0 UCSF, San Francisco, CA) suite of programs (4) and the GAFF [6] force field. Molecular trajectories were evaluated with radial distribution functions and hydrogen bond analysis.

     

     

    References

    1. Alexander, C.; Andersson, H. S.; Andersson, L. I.; Ansell, R. J.; Kirsch, N.; Nicholls, I. A.; O´Mahony, J.; Whitcombe, J., J. Mol. Recognit. (2006), 19, 106-180
    2. Nicholls, I. A.; Andersson, H. S.; Charlton, C.; Henschel, H.; Karlsson, B. C. G.; Karlsson, J. G.; O´Mahony, J.; Rosengren, A. M.; Rosengren, K. J.; Wikman, S. Biosens. Bioelectron. (2009), 25, 543-552
    3. Karlsson, B. C. G.; O´Mahony, J.; Karlsson, J. G.; Bengtsson, H.; Eriksson, L. A.; Nicholls, I. A. J. Am. Chem. Soc. (2009), 131, 13297-13304
    4. Case, D. A.; Cheatham, T. E.; Darden, T.; Gohlke, H.; Luo, R.; Merz, K. M.; Onufriev, A.; Simmerling, C.; Wang, B.; Woods, R. J. Comput. Chem. (2009), 26, 1668-1688
    5. Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. J. Comput. Chem. (2004), 25, 1157-1174

     

  • 12.
    Golker, Kerstin
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Towards Molecular Dynamics-Based Rational Design of Synthetic Polymer Recognition Systems2010Conference paper (Refereed)
    Abstract [en]

    Molecularly imprinted polymers (MIPs) are polymeric receptors with selectivity for a predetermined structure. The molecular imprinting process generates cavities in a synthetic polymer matrix that are complementary in size, shape and functionality to the template. MIPs exhibit recognition properties analogous to their biological counterparts, such as antibodies, and can be utilized in a wide range of application areas [1]. Nonetheless, the physical mechanisms underlying MIP formation and template recognition are still poorly understood. Molecular dynamics (MD) based computer simulations are a valuable theoretical tool which may be used to aid our understanding of the molecular imprinting process, and even for the development of rational design strategies [2]. Recently the first MD simulation of a complete prepolymerization mixture was presented [3].

    In the present work, MD simulations of a series of all-component prepolymerization mixtures were performed, using the local anaesthetic bupivacaine as the template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinker, 2,2’-azobis-(2-methylpropionitrile) (AIBN) as the initiator and toluene as the solvent. The simulated systems differed in the molar fraction of MAA. Systems were evaluated with radial distribution functions and hydrogen bond analyses. By correlating the results with the rebinding behaviour of a series of synthesized MIPs the importance of the stoichiometry between template, functional monomer and crosslinker was highlighted. The analysis of the MD simulations revealed strong competition for hydrogen bonding between the carbonyl oxygen’s of MAA and EGDMA and the amide proton of bupivacaine. Moreover, the hydrogen bonding contact between EGDMA and bupivacaine remained nearly unaffected by the varied molar fraction MAA in the different systems demonstrating the role of the crosslinker being more important as generally accepted.

     

    References

    [1]             Alexander, C.; Andersson, H. S.; Andersson, L. I.; Ansell, R. J.; Kirsch, N.; Nicholls, I. A.; O´Mahony, J.; Whitcombe, J., J. Mol. Recognit., 19, 106-180 (2006)

    [2]            Nicholls, I. A.; Andersson, H. S.; Charlton, C.; Henschel, H.; Karlsson, B. C. G.; Karlsson, J. G.; O´Mahony, J.; Rosengren, A. M.; Rosengren, K. J.; Wikman, S. Biosens. Bioelectron., 25, 543-552 (2009)

    [3]            Karlsson, B. C. G.; O´Mahony, J.; Karlsson, J. G.; Bengtsson, H.; Eriksson, L. A.; Nicholls, I. A. J. Am. Chem. Soc., 131, 13297-13304 (2009)

  • 13.
    Golker, Kerstin
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Towards the use of molecular dynamics as a predictive tool in the design of molecularly imprinted polymers2010Conference paper (Refereed)
    Abstract [en]

    Through the rapid increase in computational power and the development of suitable software, molecular dynamics (MD) has become a promising tool for use in the development of molecularly imprinted polymers (MIPs).1 MD is a computational method based on Newtonian mechanics, which enables the simultaneous simulation of thousands of discrete molecules, and can be used to establish the states of the molecular species present in MIP-prepolymerization mixtures. As detailed understanding of the molecular basis for formation of high affinity MIP sites is still lacking and the physical mechanism underlying specific recognition is still a matter of debate, the use of MD as a tool to investigate MIP-prepolymerization mixtures is highly motivated.1 Recently the first MD simulation of an all-component prepolymerization mixture was presented, which gave a detailed picture of the underlying monomer-template interactions important for the “molecular memory” in MIPs.2

    Here, we present results obtained from a series of MD simulations representing all-component MIP/REF prepolymerization mixtures assembled with differences in stoichiometries of functional and crosslinking monomer. In these mixtures, the local anaesthetic drug bupivacaine was used as a template, methacrylic acid as the functional monomer, ethylene dimethacrylate as crosslinking monomer, 2,2’-azobis-(2-methylpropionitrile) as the initiator and toluene as the solvent. Bupivacaine complexation in each system was evaluated with radial distribution functions and hydrogen bond analyses. By correlating the results with the rebinding behaviour of a series of synthesized bupivacaine-MIPs, the relationship between the degree of crosslinking and MIP-performance was highlighted.

    [1] Nicholls, I. A.; Andersson, H. S.; Charlton, C.; Henschel, H.; Karlsson, B. C. G.; Karlsson, J. G.; O´Mahony, J.; Rosengren, A. M.; Rosengren, K. J.; Wikman, S. Biosens. Bioelectron., 25, 543-552 (2009)

    [2] Karlsson, B. C. G.; O´Mahony, J.; Karlsson, J. G.; Bengtsson, H.; Eriksson, L. A.; Nicholls, I. A. J. Am. Chem. Soc., 131, 13297-13304 (2009)

  • 14.
    Golker, Kerstin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    A Functional Monomer Is Not Enough: Principal Component Analysis of the Influence of Template Complexation in Pre-Polymerization Mixtures on Imprinted Polymer Recognition and Morphology2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 11, p. 20572-20584Article in journal (Refereed)
    Abstract [en]

    In this report, principal component analysis (PCA) has been used to explore the influence of template complexation in the pre-polymerization phase on template molecularly imprinted polymer (MIP) recognition and polymer morphology. A series of 16 bupivacaine MIPs were studied. The ethylene glycol dimethacrylate (EGDMA)-crosslinked polymers had either methacrylic acid (MAA) or methyl methacrylate (MMA) as the functional monomer, and the stoichiometry between template, functional monomer and crosslinker was varied. The polymers were characterized using radioligand equilibrium binding experiments, gas sorption measurements, swelling studies and data extracted from molecular dynamics (MD) simulations of all-component pre-polymerization mixtures. The molar fraction of the functional monomer in the MAA-polymers contributed to describing both the binding, surface area and pore volume. Interestingly, weak positive correlations between the swelling behavior and the rebinding characteristics of the MAA-MIPs were exposed. Polymers prepared with MMA as a functional monomer and a polymer prepared with only EGDMA were found to share the same characteristics, such as poor rebinding capacities, as well as similar surface area and pore volume, independent of the molar fraction MMA used in synthesis. The use of PCA for interpreting relationships between MD-derived descriptions of events in the pre-polymerization mixture, recognition properties and morphologies of the corresponding polymers illustrates the potential of PCA as a tool for better understanding these complex materials and for their rational design.

  • 15.
    Henschel, Henning
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Insights into the Isomerisation Mechanism of Warfarin2010Conference paper (Refereed)
    Abstract [en]

    Warfarin is one of the most commonly used drugs in anticoagulent therapy. Notwithstanding its wide use, achieving correct dosage is often a major challenge due to its narrow therapeutic window.[1] The bioavailability of warfarin is believed to be greatly influenced by the environment-dependent composition of the ensemble of isomers present. While the different structures of warfarin have been discussed in earlier publications,[2] details of the mechanism underlying the formation of the cyclic hemiacetal (Figure 1) had not yet been investigated.

    Figure 1. Cyclization reaction of warfarin.

    Figure 2. Transition state in presence of one water molecule.

     

    We have now studied the reaction by means of density functional calculations. Comparison of results from calculations performed on the isolated warfarin molecule and in presence of water molecules (compare Figure 2) highlight the importance of intermolecular interactions in the key proton transfer step for the reaction to proceed. A viable model for the mechanism underlying the isomerisation shall be presented.

     

     

    References

    [1]             J. Ansell, J. Hirsh, L. Poller, H. Bussey, A. Jacobsen and E. Hylek, Chest, 126, 204S (2004).

    [2]            B. C. G. Karlsson, A. M. Rosengren, P. O. Andersson and I. A. Nicholls, J. Phys. Chem. B, 111,10520 (2007).

  • 16.
    Henschel, Henning
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    The Mechanistic Basis for Warfarin’s Structural Diversity and Implications for Its Bioavailability2010In: Journal of Molecular Structure: THEOCHEM, ISSN 0166-1280, Vol. 958, p. 7-9Article in journal (Refereed)
    Abstract [en]

    The anticoagulent drug warfarin exhibits chameleon-like isomerism, where the environment-dependent composition of the ensemble of structures greatly influences its bioavailability. Here, the mechanism of conversion between the major isomeric forms is studied. The dramatic differences in transition state energies, as determined by density functional calculations, highlight the necessity for the involvement of intermolecular interactions in the key proton transfer step. A viable model for the mechanism underlying the isomerization reactions is presented.

  • 17.
    Henschel, Henning
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Prosenc, Marc H.
    University of Hamburg, Germany.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Uppsala University.
    A Density Functional Study on the Factors Governing Metal Catalysis of the Direct Aldol Reaction2011In: Journal of Molecular Catalysis A: Chemical, ISSN 1381-1169, E-ISSN 1873-314X, Vol. 351, p. 76-80Article in journal (Refereed)
    Abstract [en]

    Density functional calculations are employed in the study of the C-C bond formation step of an aldol reaction in presence of a series of metals. Focus was placed on first row d-block metals that have been used in catalysis of direct aldol reactions. The obtained energy profiles are analysed in order to differentiate between factors governing catalysis. Results demonstrate a major influence of d-orbital occupation, and suggest some of the so far less commonly used metals as promising candidates for development of new catalytic systems.

  • 18.
    Karlsson, Björn C. G.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    The Effect of Warfarin’s Structural Diversity on Permeation Across a DPPC Bilayer Membrane2010Conference paper (Refereed)
    Abstract [en]

    Warfarin is an oral anticoagulant drug used to prevent thrombolic disorders such as myocardial infarction and stroke by inhibiting the active site of vitamin-K dependent epoxide reductase (VKOR) [1]. Despite being in widespread use and having a narrow therapeutic window, its mechanisms of action are not yet fully understood and incorrect warfarin dosage often leads to severe side effects. A factor limiting our understanding of warfarin’s bioavailability is warfarin’s structural diversity, which has been shown to be strongly affected by the nature of molecular environment e.g. solvent polarity and pH [2-7]. One of the major factors contributing to a drug’s biological effect is membrane transport, a process involving exposure of warfarin to environments of quite different character. Since a drug’s transport across membrane may include both active transport by carriers as well as diffusion-controlled processes, it may be envisaged that in order to fully predict warfarin’s anticoagulant effect these mechanisms must be carefully elucidated.

     

    Molecular dynamics (MD) simulations have previously been performed in order to obtain detailed information on static equilibrium as well as dynamic properties of small organic drugs in biomembranes. One of the most studied lipids in cell membrane simulations has been dipalmitoylphosphatidylcholine (DPPC) which is the most abundant phospholipid in cell membranes. Here we present lipid bilayer membrane transport properties for a series of warfarin structures previously reported in the literature using a fully solvated DPPC membrane model. Data extracted from simulations shed light on differences in membrane partioning as well as mobilities of warfarin isomers studied and a mechanism by which warfarin permeates through membranes in vivo is presented.

     

    References

    1. Landefeld, C.; Beyth, R. Am. J. Med. 1993, 95, 315-328.
    2. Karlsson, B. C. G.; Rosengren, A. M.; Andersson, P. O.; Nicholls, I. A. J. Phys. Chem. B 2007, 111, 10520-10528.
    3. Karlsson, B. C. G.; Rosengren, A. M.; Andersson, P. O.; Nicholls, I. A. J. Phys. Chem. B 2009, 113, 7945-7949.
    4. Karlsson, B. C. G.; Rosengren, A. M.; Näslund, I.; Andersson, P. O.; Nicholls, I. A. Submitted 2010.
    5. Rosengren, A. M.; Karlsson, B. C. G.; Näslund, I.; Andersson, P. O.; Nicholls, I. A. Submitted 2010.
    6. Nicholls, I. A.; Karlsson, B. C. G.; Rosengren, A. M.; Henschel, H. J. Mol. Recognit. 2010, In press.
    7. Henschel, H.; Karlsson, B. C. G.; Rosengren, A. M.; Nicholls, I. A. Submitted 2010.

     

  • 19.
    Karlsson, Björn C. G.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    O'Mahony, John
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Karlsson, Jesper G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Bengtsson, Helen
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Eriksson, Leif A
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Structure and Dynamics of Monomer-Template Complexation: An Explanation for Molecularly Imprinted Polymer Recognition Site Heterogeneity2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 37, p. 13297-13304Article in journal (Refereed)
    Abstract [en]

    We here present the first simulation of a complete molecularly imprinted polymer prepolymerization system. Molecular dynamics studies were performed for a system comprising a total of 1199 discrete molecules, replicating the components and concentrations employed in the corresponding polymer synthesis. The observed interactions correlate well with results obtained from (1)H NMR spectroscopic studies. Comparison with simulations performed in the absence of cross-linking agent (ethylene dimethacrylate) demonstrated its significance in the formation of ligand recognition sites. Moreover, the influence of events such as template-template (bupivacaine) and monomer-monomer (methacrylic acid) self-association, porogen-template interactions, and template conformational variability was revealed. The template recognition capacity of the modeled polymer system was verified by synthesis of imprinted and reference polymers and subsequent radioligand binding Analysis. Collectively, through a series of statistical analyses of molecular trajectories in conjunction with spectroscopic data it was demonstrated that an ensemble of complex structures is present in the prepolymerization mixture and that this diversity is the basis for the binding site heterogeneity observed in molecularly imprinted polymers (MIPs) prepared using the noncovalent strategy.

  • 20.
    Karlsson, Björn C. G.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren, Annika M.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Per Ola
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecular Insights on the Two Fluorescence Lifetimes Displayed by Warfarin from Fluorescence Anisotropy and Molecular Dynamics Studies2009In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, no 22, p. 7945-7949Article in journal (Refereed)
    Abstract [en]

    A series of steady-state fluorescence anisotropy experiments has been performed to demonstrate the presence of a deprotonated open side chain form of warfarin in organic environments. We explain the observed emission-wavelength-dependent anisotropy of warfarin in ethanol, 2-propanol, and acetonitrile due to the coexistence of neutral isomers and deprotonated open side chain forms displaying different fluorescence decay kinetics. To investigate solvent-solute interactions in more detail, a series of molecular dynamics simulations was performed to study warfarin solvation and to predict the time scale of rotational diffusion displayed by this compound. Predictions obtained provide an explanation for the nonzero values in anisotropy observed for neutral isomers of warfarin associated with the short fluorescence lifetime (tau < 0.1 ns) and for an approximately zero anisotropy observed for the deprotonated open side chain form, which is associated with the longer fluorescence lifetime (tau = 0.5-1.6 ns). Finally, we address the potential use of fluorescence anisotropy for an increased understanding of the structural diversity of warfarin in protein binding pockets.

  • 21.
    Karlsson, Björn C. G.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Näslund, Inga
    FOI, Swedish Defence Research Agency.
    Andersson, Per Ola
    FOI, Swedish Defence Research Agency.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    A molecularly imprinted polymer-based detection of Warfarin using time resolved fluorescence spectroscopy2010Conference paper (Refereed)
    Abstract [en]

    Warfarin is a clinically important drug widely used in the treatment of thrombolic disorders e.g. myocardial infarction and stroke.1 When administered, 99% of the drug present in blood is bound to the transport protein human serum albumin (HSA).2 On account of the fact that HSA demonstrates polymorphism and warfarin has a narrow therapeutic index, careful monitoring of the effect of drug-dosage must be performed.

    Currently, warfarin’s anticoagulant effect is measured by an indirect method in which the clotting time is measured and correlated to the amount of warfarin present. As current methods for self-monitoring are limited, the development of alternative robust and more sensitive methods is desirable.

    In this study, we have developed a non-covalent molecularly imprinted polymer3 (MIP) system with selectivity for warfarin.4 The HSA-like binding properties of this MIP were established in previous efforts to develop polymers capable of HSA-like binding of warfarin.5

    In principle, the fluorophoric nature of warfarin should allow for the fluorescence spectroscopy-based detection of the drug. Recent efforts by us,6-8 using a series of theoretical and spectroscopic studies have highlighted the complex nature of warfarin. In particular, the medium dependent isomerization of this drug illustrates why spectroscopy based methods for the direct detection of the drug has not been forthcoming. Results from these studies have been used to develop a method for the in situ detection of warfarin using time resolved fluorescence spectroscopy.

    (1)      Landefeld, C.; Beyth, R. Anticoagulant-related bleeding - epidemiology, prediction and prevention. Am. J. Med. 1993, 95, 315-328.

    (2)      Yacobi, A.; Udall, J. A.; Levy, G. Comparative pharmacokinetics of coumarin anticoagulants.18 Serum-protein binding as a determinant of warfarin body clearance and anticoagulant effect. Clin. Pharmacol Ther. 1976, 19, 552-558.

    (3)      Alexander, C.; Andersson, H. S.; Andersson, L. I.; Ansell, R. J.; Kirsch, N.; Nicholls, I. A.; O'Mahony, J.; Whitcombe, M. J. Molecular imprinting science and technology: A survey of the literature for the years up to and including 2003. Journal of Molecular Recognition 2006, 19, 106-180.

    (4)      Rosengren, A. M.; Karlsson, B. C. G.; Näslund, I.; Andersson, P. O.; Nicholls, I. A. Time resolved fluorescence spectroscopic detection of the anticoagulant warfarin: A sensor-based method for direct detection in blood plasma. 2010, Submitted.

    (5)      Karlsson, B. C. G.; Rosengren, A. M.; Näslund, I.; Andersson, P. O.; Nicholls, I. A. Synthetic Human Serum Albumin Sudlow I binding site mimics. 2010, Submitted.

    (6)      Karlsson, B. C. G.; Rosengren, A. M.; Andersson, P. O.; Nicholls, I. A. The Spectrophysics of Warfarin: Implications for Protein Binding J. Phys. Chem. B 2007, 111, 10520-10528.

    (7)      Karlsson, B. C. G.; Rosengren, A. M.; Andersson, P. O.; Nicholls, I. A. Molecular Insights on the Two Fluorescence Lifetimes Displayed by Warfarin from Fluorescence Anisotropy and Molecular Dynamics Studies. J. Phys. Chem. B 2009, 113, 7945-7949.

    (8)      Nicholls, I. A.; Karlsson, B. C. G., Rosengren, A. M.. Henschel, H. Warfarin: an Environment-Dependent Switchable Molecular Probe. J. Mol. Recognit. 2010, in press.

  • 22.
    Kathiravan, Subban
    et al.
    Linnaeus Univ, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.;Linnaeus Univ, Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Linnaeus Univ, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.;Linnaeus Univ, Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Cobalt Catalyzed, Regioselective C(sp(2))-H Activation of Amides with 1,3-Diynes2017In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 19, no 18, p. 4758-4761Article in journal (Refereed)
    Abstract [en]

    The development of a first row transition metal (cobalt)-based catalyst for the as yet unexplored CH activation-driven reaction of 1,3-diynes, themselves a functional class of interest in a range of application areas, to form isoquinolinonesan important structural motif in a number of biologically active substancesis presented. This versatile and inexpensive catalyst employs a covalently attached bidendate-directing group, 8-aminoquinoline. The template directs the CH activation and facilitates the synthesis of a wide range of alkynylated heterocycles under mild conditions and with excellent regioselectivity. This strategy provides a novel and efficient route to diverse heterocyclic frameworks as demonstrated by its late stage application in bisheterocycle syntheses.

  • 23.
    Kathiravan, Subban
    et al.
    Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, S-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, S-39182 Kalmar, Sweden..
    Monoprotected L-Amino Acid (L-MPAA), Accelerated Bromination, Chlorination, and Iodination of C(sp²)-H Bonds by Iridium(III) Catalysis2017In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, no 29, p. 7031-7036Article in journal (Refereed)
    Abstract [en]

    Halogenated arenes are important structural motifs commonly found in biologically active molecules and used for a variety of transformations in organic synthesis. Herein, we report the mono-protected L-amino acid (L-MPAA) accelerated iridium(III)-catalyzed halogenation of (hetero)anilides at room temperature. This reaction constitutes the first example of an iridium(III)/L-MPAA-catalyzed general halogenation of (hetero)arenes through C(sp²)-H activation. Furthermore, we demonstrate the potential utility of our method through its use in the synthesis of a quinolone derivative.

  • 24.
    Kathiravan, Subban
    et al.
    Linnaeus Univ, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.;Linnaeus Univ, Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. Linnaeus Univ, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.;Linnaeus Univ, Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Rhodium(III)-catalysed, redox-neutral C(sp(2))-H alkenylation using pivalimide as a directing group with internal alkynes2017In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 58, no 1, p. 1-4Article in journal (Refereed)
    Abstract [en]

    In the presence of [RhCp*Cl(2)l(2), N-pivaloyl anilines react with internal alkynes to give the corresponding 2-alkenylpivalimides under redox neutral conditions through C-H activation. This redox neutral hydroarylation, which does not require an external organic acid, unlocks a regioselective synthetic route to 2-alkenyl anilines and is generally applicable to diversely substituted electron rich and electron poor pivalimides.

  • 25.
    Kathiravan, Suppan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Cobalt Catalyzed, Regioselective C(sp(2))-H Activation of Amides with 1,3-Diynes2017In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 19, no 18, p. 4758-4761Article in journal (Refereed)
    Abstract [en]

    The development of a first row transition metal (cobalt)-based catalyst for the as yet unexplored CH activation-driven reaction of 1,3-diynes, themselves a functional class of interest in a range of application areas, to form isoquinolinonesan important structural motif in a number of biologically active substancesis presented. This versatile and inexpensive catalyst employs a covalently attached bidendate-directing group, 8-aminoquinoline. The template directs the CH activation and facilitates the synthesis of a wide range of alkynylated heterocycles under mild conditions and with excellent regioselectivity. This strategy provides a novel and efficient route to diverse heterocyclic frameworks as demonstrated by its late stage application in bisheterocycle syntheses.

  • 26.
    Kathiravan, Suppan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala university.
    Palladium Catalyzed Vinyltrifluoromethylation of Aryl Halides through Decarboxylative Cross-Coupling with 2-(Trifluoromethyl)acrylic Acid2015In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 17, p. 1874-1877Article in journal (Refereed)
    Abstract [en]

    An efficient Pd-catalyzed stereoselective vinyltrifluoromethylation of aryl halides, through decarboxylative cross-coupling with 2-(trifluoromethyl)acrylic acid is described. The ready availability of the starting materials, the high level of functional group tolerance, and excellentE/Z selectivity make this protocol a safe and operationally convenient strategy for efficient synthesis of vinyltrifluoromethyl derivatives.

  • 27.
    Kathiravan, Suppan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Rhodium-Catalyzed Oxidative Perfluoroalkenylation by Carbonyl Group Directed C-H Bond Activation2014In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 32, p. 7211-7219Article in journal (Refereed)
    Abstract [en]

    The selective activation of C-H bonds under mild Rh-III catalytic conditions has been developed for the perfluoroalkenylation of various cyclic and acyclic aromatic ketones. This protocol uses versatile reagents and mild conditions. It requires a very low catalyst loading and has exceptional functional group tolerance as well as provides products in good to excellent yields. An application of this approach was described for the preparation of perfluoroethyl acrylate derivatives of biologically active substances.

  • 28.
    Kathiravan, Suppan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Rhodium(III)-catalysed aerobic synthesis of highly functionalized indoles from N-arylurea under mild conditions through C-H activation2014In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 50, no 95, p. 14964-14967Article in journal (Refereed)
    Abstract [en]

    A Rh(III) catalysed amino arylation of alkynes using copper as the terminal oxidant for regeneration of the catalytically active species under aerobic conditions is described. This novel C-H activation reaction was applied to the synthesis of a wide range of substituted indoles from N-arylureas.

  • 29.
    Kirsch, Nicole
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Hedin-Dahlström, Jimmy
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Henschel, Henning
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Whitcombe, Michael J
    Wikman, Susanne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Molecularly imprinted polymer catalysis of a Diels-Alder reaction2009In: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, E-ISSN 1873-3158, Vol. 58, no 1-4, p. 110-117Article in journal (Refereed)
    Abstract [en]

    A series of synthetic polymers were designed and synthesized for enhancing the rate of the Diels-Alder cycloaddition reaction of 1,3-butadiene carbamic acid benzyl ester (11) and N,N-dimethyl acrylamide (2), to yield the corresponding endo- (3) and exo- (4) reaction products. Putative transition state analogues (TSAs) for the endo- (5) and exo- (6) reaction pathways were used as templates for the synthesis of molecularly imprinted methacrylic acid (MAA)-divinylbenzene (DVB) copolymers. The polymer system utilized was selected based upon a series of (1)H NMR studies of complex formation between template and a functional monomer analogue (K(d) (app) approximate to 70 mM, d(8)-toluene, 293 K). Batch binding studies revealed that the imprinted polymers were selective for the TSA corresponding to the template used in the polymer synthesis. Studies on the influence of the polymers on the catalysis of the reaction of 1 and 2 demonstrated a 20-fold enhancement of the rate of the reaction relative to the solution reaction. A surprising temperature dependence of the reaction of 1 and 2 in the presence of the polymers was observed, which provides support for the role of template-functional monomer complexes in the catalysis of the Diels-Alder reaction.

  • 30. Knutsson, M
    et al.
    Andersson, Håkan S.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Novel chiral recognition elements for molecularly imprinted polymer preparation1998In: Journal of Molecular Recognition, Vol. 11, p. 87-90Article in journal (Refereed)
  • 31.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Towards the Rational Design of Functional Molecularly Imprinted Polymers2010Conference paper (Refereed)
  • 32.
    Nicholls, Ian A.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Adbo, Karina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Håkan S.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Per-Ola
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Ankarloo, Jonas
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Hedin-Dahlström, Jimmy
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Jokela, Päivi
    University of Kalmar, School of Communication and Design.
    Karlsson, Jesper G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Olofsson, Linus
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Shoravi, Siamak
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Svenson, Johan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Wikman, Susanne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Can we rationally design molecularly imprinted polymers?2001In: Analytica Chimica Acta, Vol. 435, no 1, p. 9-18Article in journal (Refereed)
  • 33.
    Nicholls, Ian A.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Håkan S.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Thermodynamic principles underlying molecularly imprinted polymer formation and ligand recognition2000Other (Other academic)
  • 34.
    Nicholls, Ian A.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Håkan S.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Charlton, Christy
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Henschel, Henning
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Karlsson, Björn C. G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Karlsson, Jesper G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    O'Mahony, John
    Rosengren, Annika M.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren, K. Johan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Wikman, Susanne
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Theoretical and Computational Strategies for Rational Molecularly Imprinted Polymer Design2009In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 25, no 3, p. 543-552Article in journal (Refereed)
    Abstract [en]

    The further evolution of molecularly imprinted polymer science and technology necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. A combination of the rapid growth in computer power over the past decade and significant software developments have opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers. 

  • 35.
    Nicholls, Ian A.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Golker, Kerstin
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Henschel, Henning
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Shoravi, Siamak
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wikman, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rational Design of Biomimetic Molecularly Imprinted Materials: Theoretical and Computational Strategies for Guiding Nanoscale Structured Polymer Development2011In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 400, p. 1771-1786Article, review/survey (Refereed)
    Abstract [en]

    In principle, molecularly imprinted polymer science and technology provides a means for ready access to nano-structured polymeric materials of predetermined selectivity. The versatility of the technique has brought it to the attention of many working with the development of nanomaterials with biological or biomimetic properties for use as therapeutics or in medical devices. Nonetheless, the further evolution of the field necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. The rapid growth in computer power and software over the past decade has opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.

  • 36.
    Nicholls, Ian A.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Golker, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Henschel, Henning
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Shoravi, Siamak
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wikman, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rational molecularly imprinted polymer design: theoretical and computational strategies2013In: Molecular Imprinting: Principles and Applications of Micro- and Nanostructured Polymers / [ed] Ye, L, London: Pan Stanford Publishing, 2013, p. 71-104Chapter in book (Refereed)
  • 37.
    Nicholls, Ian A.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Per-Ola
    Karlsson, Björn C. G.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren, Annika M.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Method and apparatus for detecting pharmaceuticals in a sample2009Patent (Other (popular science, discussion, etc.))
  • 38.
    Nicholls, Ian A.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Andersson, Per-Ola
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Method and apparatus for detecting pharmaceuticals in a sample2010Patent (Other (popular science, discussion, etc.))
  • 39.
    Nicholls, Ian A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Chavan, Swapnil
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Golker, Kerstin
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Karlsson, Björn C. G.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Olsson, Gustaf D.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Rosengren, Annika M.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Suriyanarayanan, Subramanian
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Wiklander, Jesper G.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Theoretical and Computational Strategies for the Study of the Molecular Imprinting Process and Polymer Performance2015In: Molecularly Imprinted Polymers In Biotechnology, Cham, Switzerland: Springer, 2015, p. 25-50Chapter in book (Refereed)
    Abstract [en]

    The development of in silico strategies for the study of the molecular imprinting process and the properties of molecularly imprinted materials has been driven by a growing awareness of the inherent complexity of these systems and even by an increased awareness of the potential of these materials for use in a range of application areas. Here we highlight the development of theoretical and computational strategies that are contributing to an improved understanding of the mechanisms underlying molecularly imprinted material synthesis and performance, and even their rational design.

  • 40.
    Nicholls, Ian A.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala Univ, Dept Chem BMC, SE-75123 Uppsala, Sweden.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Computational Strategies for the Design and Study of Molecularly Imprinted Materials2013In: Industrial & Engineering Chemistry Research, ISSN 0888-5885, E-ISSN 1520-5045, Vol. 52, no 39, p. 13900-13909Article in journal (Refereed)
    Abstract [en]

    The need for materials with predetermined ligand-selectivities for use in sensing and separation technologies, e.g. membranes and chromatography, has driven the development of molecularly imprinted polymer science and technology. Over recent years, the need to develop robust predictive tools capable of handling the complexity of molecular imprinting systems has become apparent The current status of the use of in silica techniques in molecular imprinting is here presented, and we highlight areas where new developments are contributing to improvements in the rational design of molecularly imprinted polymers.

  • 41.
    Nicholls, Ian A.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Moledcular Imprints2009Patent (Other (popular science, discussion, etc.))
  • 42. Norell, M S
    et al.
    Andersson, Håkan S.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Theophylline molecularly imprinted polymer dissociation kinetics: A novel sustained release drug dosage mechanism1998In: Journal of Molecular Recognition, Vol. 11, p. 98-102Article in journal (Refereed)
  • 43.
    Olsson, Gustaf D.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Schillinger, Eric
    Sellergren, Börje
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala Univ, Dept Chem BMC, SE-75123 Uppsala, Sweden.
    Theoretical Studies of 17-beta-Estradiol-Imprinted Prepolymerization Mixtures: Insights Concerning the Roles of Cross-Linking and Functional Monomers in Template Complexation and Polymerization2013In: Industrial & Engineering Chemistry Research, ISSN 0888-5885, E-ISSN 1520-5045, Vol. 52, no 39, p. 13965-13970Article in journal (Refereed)
    Abstract [en]

    In this study, computational methods were employed in efforts to elucidate physical mechanisms underlying the ligand selectivity of polymeric sorbents produced through the molecular imprinting of 17-beta-estradiol. Previous computational and experimental studies had identified candidate systems applicable to the development of synthetic polymeric receptors for the detection and possible removal of pollutants with endocrine-disrupting properties. Here we present a series of comprehensive molecular dynamics studies of candidate molecular imprinting prepolymerization systems. The results from the studies highlight the role of the cross-linker and the importance of the interplay between functionalities of the various monomers employed in template complexation. The significance of these results for future studies is discussed.

  • 44.
    Olsson, Gustaf D.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Shoravi, Siamak
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Mechanisms Underlying Molecularly Imprinted Polymer Molecular Memory and The Role of Crosslinker: Resolving Debate on the Nature of Template Recognition in Phenylalanine Anilide Imprinted Polymers2012In: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 25, no 2, p. 69-73Article in journal (Refereed)
    Abstract [en]

    A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilide imprinted co-(ethylene glycol dimethacrylate-methacrylic acid) molecularly imprinted polymers have been employed to investigate the mechanistic basis for template selective recognition in these systems. This has provided new insights on the mechanisms underlying template recognition, in particular the significant role played by the crosslinking agent. Importantly, the study supports the occurrence of template self-association events that allows us to resolve debate between the two previously proposed models used to explain this system's underlying recognition mechanisms. Moreover, the complexity of the molecular level events underlying template complexation is highlighted by this study, a factor that should be considered in rational molecularly imprinted polymer design, especially with respect to recognition site heterogeneity.

  • 45.
    Olsson, Gustaf D.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Mechanism of Phenylalanine Anilide Molecularly Imprinted Polymer - Template Recognition: The Role of Template Dimerization2010Conference paper (Refereed)
    Abstract [en]

    It is now widely accepted that the recognition properties of a MIP are derived from molecular level events present during the prepolymerization stage.1 Studies regarding the nature and extent of template complexation during this stage should therefore yield valuable information regarding the template recognition properties of the final MIP. One method of great potential for illuminating molecular level details in this area of MIP research is molecular dynamics (MD).2 MD simulations enable studies of molecular-level events in MIP prepolymerization mixtures.

    Phenylalanine anilide (PA) is a molecule that has been extensively used as a template in a series of seminal molecular imprinting studies.3-5 In an effort to elucidate the origin to the imprinting effect, Sellergren, Lepistö and Mosbach proposed that selective high-affinity sites in the PA-MIP were based on functional monomer-template complexation of a 2:1 stoichiometry.3 In a follow-up study, Katz and Davis presented results that revealed further information regarding the origin of recognition in PA-MIPs.5 It was suggested that the template recognition sites were based on functional monomer-template complexes of 1:1 stoichiometry, and also that the formation of higher order template-template complexes has important effects on the final PA-MIP recognition properties. In light of this conjecture and several more recent studies highlighting the diversity of template complexation mechanisms in prepolymerization mixtures, have pointed at the complexity and diversity in the ensemble of complexes leading to the final “molecular memory”.

    Here we present the novel insights into the molecular basis for PA-MIP template recognition derived from a series of MD simulations of the PA-MIP prepolymerisation systems. Data support the presence of PA-PA complexes and that the most statistically prevalent stoichiometry functional monomer-PA complexes was 1:1. The role of cross-linker is also discussed. This study highlights the potential of all component MD studies for rational MIP design.

     

    (1)      Alexander, C.; Andersson, H.S.; Andersson, L.I.; Ansell, R.J.; Kirsch, N.; Nicholls, I.A.; O'Mahony, J.; Whitcombe, M.J.  Molecular imprinting science and technology: A survey of the literature for the years up to and including 2003. Journal of Molecular Recognition 2006, 19, 106-180.

    (2)      Nicholls, I.A.; Andersson, H.S.; Charlton, C; Henschel, H.; Karlsson, B.C.G.; Karlsson, J.G.; O’Mahony, J.; Rosengren, A.M.; Rosengren, J.K.; Wikman, S. Theoretical and computational stratgies for rational molecularly imprinted polymer design. Biosensors and Bioelectronics 2009, 25, 543-552

    (3)      Sellergren, B.; Lepistoe, M.; Mosbach, K.. Highly enantioselective and substrate-selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognition. Journal of American Chemical Society 1988, 110, 5853-5860

    (4)      Sellergren, B.. Molecular imprinting by noncovalent interactions: Tailor-made chiral stationary phases of high selectivity and sample load capacity. Chirality 1989, 1, 63-68

    (5)      Katz, A.; Davis, M.E. Investigations into the mechanism of molecular recognition with imprinted polymers. Macromolecules 1999, 32, 4113-4121

  • 46.
    Olsson, Gustaf D.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Shoravi, Siamak
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    The nature and extent of interactions in phenylalanine anilide molecularly imprinted polymer prepolymerisation mixtures: a new model for the basis for ligand-selective recognition2010Conference paper (Refereed)
    Abstract [en]

    In this work, classical molecular dynamics (MD) simulations have been used to provide unique insights on the nature and extent of intermolecular interactions present in a phenylalanine anilide (PA) molecularly imprinted polymers (MIP) prepolymerization mixture.

    Molecular Imprinting is a technique for producing highly selective synthetic receptors for a predetermined molecular structure, and involves the formation of cavities in a synthetic polymer matrix that are of complementary functional and structural character to a template molecule.1 It is generally accepted that the recognition properties of a MIP is a product of the interactions between monomers and template during the prepolymerization stage. Accordingly, studies of the nature and extent of the interactions present in prepolymerization mixtures, in patricular those involving template, should yield information which can be related to the observed recognition properties of the final MIP.

    Phenylalanine anilide MIPs have been the subject of a significant number of studies aimed at producing an understanding of the mechanisms underlying the recognition processes. Interestingly, two different models have been proposed to explain the behaviour of PA-MIPs. Studies by Sellergren et al. proposed that template selectivity, was a consequence of  the presence of a functional monomer-template complexes of 2:1 stoichiometry.2 Later, however, Katz and Davis proposed an alternative model,3 where the template (PA) recognition sites in the MIP were suggested to arise from functional monomer-template complexes of 1:1 stoichiometry in combination with the presence of higher order template-template complexes.

    To resolve this conjecture, we performed a series of MD studies, the results of which demonstrated both the presence of PA-PA self association complexes, and that the most statistically prevalent monomer-PA complex stoichiometry was of a 1:1 nature, though differetn in character from that proposed by Katz and Davis.  Moreover, the role of cross-linker in forming recognition sites was apparnet in these studies, a fact not previously considered.

     

    References

    1. Alexander C, Andersson HS, Andersson LI, Ansell RJ, Kirsh N, Nicholls IA, O’Mahony J, Whitcombe MJ. Molecular imprinting science and technology: A survey of the literature for the years up to and including 2003. Journal of Molecular Recognition 2006;19:106-180
    2. Sellergren B, Lepistö M, Mosbach K. Highly enantioselective and substrate selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognition. Journal of the American Chemical Society 1988;110:5853-5860
    3. Katz A, Davis ME. Investigations into the mechanisms of molecular recognition with imprinted polymers. Macromolecules 1999;32:4113-4121

     

  • 47.
    Olsson, Gustaf D.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Shoravi, Siamak
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    The Nature and Extent of Template-Template Complexation in Phenylalanine Anilide Molecularly Imprinted Polymers2010Conference paper (Refereed)
    Abstract [en]

    The molecular imprinting technique has received significant attention due to its utility in the production of synthetic polymeric materials with predetermined ligand recognition properties [1].

    It is generally accepted that the recognition properties of a molecularly imprinted polymer (MIP) is established during the prepolymerization stage. Previous investigations on the nature and extent of template prepolymerization complexation in a phenylalanine anilide (PA) MIP pointed at the complexity and diversity in the ensemble of complexes leading to the final “molecular memory”. In particular, conflicting models have been used to explain the observed molecular memory. Sellergren, Lepistö and Mosbach [2] proposed that selective, high-affinity sites in the final MIP were based on functional monomer-PA complexation of a 2:1 stoichiometry. Later, Katz and Davis [3] proposed that the template recognition sites arose due to a 1:1 functional monomer-template complex stoichiometry and that the effect of template dimerization is critical for the observed PA-MIP recognition properties.

    In this study, we have attempted to shed new light on this as yet unresolved conflict using a series of molecular dynamics (MD) simulations. Results demonstrated the presence of PA-PA complexes and that the most statistically prevalent stoichiometry of functional monomer-PA complexes was of 1:1.

    [1]             Alexander C, Andersson HS, Andersson LI, Ansell R, Kirsch N, Nicholls IA et al. Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003, Journal of Molecular Recognition, 19, 106-180 (2006).

    [2]            Sellergren B, Lepistö M, Mosbach K. Highly enantioselective and substrate selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognition, Journal of the American Chemical Society, 110, 5853-5860 (1988).

    [3]             Katz A, Davis ME. Investigations into the mechanisms of molecular recognition with imprinted polymers, Macromolecules, 32, 4113-4121 (1999).

  • 48.
    Olsson, Gustaf D.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Niedergall, Klaus
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Germany..
    Bach, Monika
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Germany ; Univ Stuttgart, Inst Interfacial Engn & Plasmatechnol IGVT, Germany.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Linnaeus University Centre for Biomaterials Chemistry.
    Tovar, Guenter
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Germany ; Univ Stuttgart, Inst Interfacial Engn & Plasmatechnol IGVT, Germany.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Simulation of imprinted emulsion prepolymerization mixtures2015In: Polymer journal, ISSN 0032-3896, E-ISSN 1349-0540, Vol. 47, no 12, p. 827-830Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to develop protocols for and evaluate the use of all-atom full system molecular dynamic (MD) simulations of emulsion systems in the development of molecularly imprinted polymers (MIPs). Here, we report on the first, to the best of our knowledge, use of all-component MD studies to simulate and evaluate MIP miniemulsion prepolymerization mixtures; in this case, the mixtures used in the synthesis of a series of MIP-nanoparticles (MIP-NPs).

  • 49. O'Mahony, John
    et al.
    Moloney, Mary
    McCormack, Martin
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Mizaikoff, Boris
    Danaher, Martin
    Design and implementation of an imprinted material for the exaction of the endocrine disruptor bisphenol A from milk2013In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 931, p. 164-169Article in journal (Refereed)
    Abstract [en]

    This paper describes the determination of bisphenol A (BPA) in milk samples, using a novel molecularly imprinted polymer. The imprinted polymer was developed using a rational design approach, and pre-polymerization interactions were investigated using molecular dynamics simulations and X-ray crystallography. A hydroquinone-imprinted polymer was used for solid phase extraction (SPE) clean-up of samples. BPA was quantified by high performance liquid chromatography (HPLC) and fluorescence (FLD) detection. Following validation, the method described was capable of determining bisphenol A in milk down to a limit of detection of 1.32 mu g kg(-1). The method was applied to a survey (n = 27) of commercial milk products; BPA was detected in one of the samples, at a level of 176 mu g kg(-1). Test results were confirmed by a parallel UHPLC-MS/MS analytical method. This demonstrates the utility of the hydroquinone-imprinted polymer for application to selective sample clean-up and analysis of bisphenol A in milk, avoiding possible detrimental affects associated with template bleeding and without the need for expensive or difficult-to-obtain template. (C) 2013 Elsevier B.V. All rights reserved.

  • 50.
    Oskarsson, Louise
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Söderberg, Pernilla
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Towards Phage Display-Derived Synthetic Receptors for Adenine2010Conference paper (Refereed)
    Abstract [en]

    The expression of peptides on phage coat proteins via genetic engineering was first achieved in 1985 [1] and was followed by the construction of phage display combinatorial libraries in 1990 [2].  Phage display combinatorial libraries have been used not only to find peptides that interact with various biomolecules such as receptors, antibodies, enzyme active sites, and protein surfaces, but also to find peptides with affinity for metals and plastics and with function in non-biological environments [3].

    In this study, we have challenged a cyclic heptamer phage display library with surfaces adenine functionalised surfaces with the aim of identifying peptide motifs selective for adenine. The synthesis and characterisation of surfaces, and results from phage display screening shall be presented.

     

     

    [1] Smith, G.P. Science (1985) 228, 1315-1317.

    [2] Scott, J.K.; Smith, G.P. Science (1990) 249, 386-390.

    [3] Olofsson, L.; Söderberg, P.; Ankarloo, J.; Nicholls, I.A. J. Mol. Recognit. (2008) 19, 18-25.

12 1 - 50 of 77
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