| 1. |
- Nicholls, Ian A., et al.
(författare)
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Rational design of biomimetic molecularly imprinted materials : theoretical and computational strategies for guiding nanoscale structured polymer development
- 2011
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:6, s. 1771-1786
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 2. |
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| 3. |
- Olsson, Gustaf D., et al.
(författare)
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Mechanism of Phenylalanine Anilide Molecularly Imprinted Polymer - Template Recognition: The Role of Template Dimerization
- 2010
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Konferensbidrag (refereegranskat)abstract
- 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
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| 4. |
- Olsson, Gustaf D., et al.
(författare)
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Mechanisms underlying molecularly imprinted polymer molecular memory and the role of crosslinker : resolving debate on the nature of template recognition in phenylalanine anilide imprinted polymers
- 2012
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Ingår i: Journal of Molecular Recognition. - : Wiley. - 0952-3499 .- 1099-1352. ; 25:2, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Olsson, Gustaf D., et al.
(författare)
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The nature and extent of interactions in phenylalanine anilide molecularly imprinted polymer prepolymerisation mixtures: a new model for the basis for ligand-selective recognition
- 2010
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Konferensbidrag (refereegranskat)abstract
- 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. ReferencesAlexander 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;19:106-180Sellergren 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;110:5853-5860Katz A, Davis ME. Investigations into the mechanisms of molecular recognition with imprinted polymers. Macromolecules 1999;32:4113-4121
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| 6. |
- Olsson, Gustaf D., et al.
(författare)
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The Nature and Extent of Template-Template Complexation in Phenylalanine Anilide Molecularly Imprinted Polymers
- 2010
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Konferensbidrag (refereegranskat)abstract
- 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).
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| 7. |
- Shoravi, Siamak, et al.
(författare)
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Towards Synthetic Neuraminidases
- 2010
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Konferensbidrag (refereegranskat)abstract
- Influenza endemics and pandemics have been a menace to humanity through the ages and pose ominous threats and with dire consequences for humanity [1]. A better understanding of the virus, the epidemiology of the disease, and its structure and function is essential for creating new therapies and even for better understanding resistance to existing treatments. At the molecular level the two capside proteins Neuraminidase and Hemagglutinin are engaged in interactions with host cell surface sialic acid residues, and are critical for contagion and budding off of the virus into and from the cell, and have been the targets for drug development strategies [2]. The rise of strains of the virus resistant to drugs targeting Neuraminidase make it crucial to develop techniques for better understanding of the virus and hence design of better antiviral agents [3].In this study a combination of molecular dynamics (MD) and NMR spectroscopy [4-7] is been utilised in order to screen some 60 polymers for candidate systems [8] for use in the preparation of synthetic polymer neauraminidase mimics. Progress in the design, synthesis and evaluation of these materials shall be presented.References1. Webster et al., Microbiol. Rev., 56, 152-175 (1992).2. von Itzstein et al., Nature, 263, 418-423 (1993).3. Lindberg et al., Chemosphere, 57, 1479-1488. (2004).4. Svensson et al., J. Chromatogr. A, 1024, 39-44 (2004).5. O’Mahony et al., Analyst, 23, 1147-1115 (2007).6. Karlsson et al., J. Am. Chem. Soc., 131, 13297-13304 (2009).7. Nicholls et al., Biosens. Bioelectron., 25, 553-557 (2009).8. Shoravi et al., unpublished results (2010).
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| 8. |
- Wiklander, Jesper G., et al.
(författare)
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A synthetic polymer with avidin-like binding properties
- 2010
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Konferensbidrag (refereegranskat)abstract
- A series of streptavidin mimicking molecularly imprinted polymers has been developed and evaluated for their biotin binding characteristics. A combination of molecular dynamics and NMR spectroscopy was used to examine potential polymer systems, in particular with the functional monomers methacrylic acid and 2-acrylamidopyridine. Synthesis of co-polymers of ethylene dimethacrylate and one or both of these functional monomers was performed. A combination of radioligand binding studies and surface area analyses (BET, SEM) demonstrated the presence of selectivity in polymers prepared using methacrylic acid as functional monomer. This correlated well with the molecular dynamics studies, showing the power of this methodology as a prognostic tool for predicting the behaviour of molecularly imprinted polymers.
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| 9. |
- Wiklander, Jesper G., 1974-, et al.
(författare)
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Towards a synthetic avidin mimic
- 2011
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:5, s. 1397-1404
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Tidskriftsartikel (refereegranskat)abstract
- A series of streptavidin-mimicking molecularly imprinted polymers has been developed and evaluated for their biotin binding characteristics. A combination of molecular dynamics and NMR spectroscopy was used to examine potential polymer systems, in particular with the functional monomers methacrylic acid and 2-acrylamidopyridine. The synthesis of copolymers of ethylene dimethacrylate and one or both of these functional monomers was performed. A combination of radioligand binding studies and surface area analyses demonstrated the presence of selectivity in polymers prepared using methacrylic acid as the functional monomer. This was predicted by the molecular dynamics studies showing the power of this methodology as a prognostic tool for predicting the behavior of molecularly imprinted polymers.
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| 10. |
- Chavan, Swapnil, et al.
(författare)
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Towards Global QSAR Model Building for Acute Toxicity : Munro Database Case Study
- 2014
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 15:10, s. 18162-18174
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Tidskriftsartikel (refereegranskat)abstract
- A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.
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