Håkan S. Andersson

Theoretical and computational strategies for rational molecularly imprinted polymer design

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.

Can we rationally design molecularly imprinted polymers

The nearly exponential growth in the molecular imprinting literature has to a large extent been fuelled by an increasing awareness of the potential of molecular imprinting based technologies. Despite the acceptance of the technique by cognate disciplines and the demonstration of its usefulness in a number of enabling technologies, relatively little is known about the molecular level events underlying the imprinting process and subsequent recognition events. What rules govern imprint formation? Can we use such rules to rationally design molecularly imprinted polymers?

Theophylline molecularly imprinted polymer dissociation kinetics: A novel sustained release drug dosage mechanism

The template release kinetics of theophylline molecularly imprinted polymers has been examined with a view to determining their potential as a controlled release drug dosage form. The basis for the ligand selectivity of these polymers has been shown through the demonstration of pre‐polymerization template– monomer complexation and HPLC studies of the product polymer ligand selectivities. The release kinetics shows a dependence upon template loading and pH. Small differences in release characteristics between imprinted and non‐imprinted (reference) polymers have been observed. Copyright

Rational design of biomimetic molecularly imprinted materials: theoretical and computational strategies for guiding nanoscale structured polymer development

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.

Spectroscopic studies of the molecular imprinting self-assembly process

A method for the rapid estimation of the extent of complex formation in molecular imprinting pre‐polymerization mixtures is described. By the use of a UV spectroscopy titration procedure, apparent binding constants for such self‐assembly processes have been obtained. This method was used for comparison of the interactions between a dipeptide template (N‐acetyl‐L‐phenylalaninyl‐L‐tryptophanyl methyl ester) and the functional monomer methacrylic acid, and the monomer analogues acetic acid and trifluoroacetic acid. The importance of template–monomer association during the molecular imprinting pre‐polymerization phase is discussed with respect to the systems studied. Copyright

Study of the Nature of Recognition in Molecularly Imprinted Polymers

In the present study molecularly imprinted polymers (MIPs) were prepared against a series of structurally related compounds containing various numbers of pyridyl groups. The goal, to increase understanding of the mechanisms of recognition in MIPs, was achieved by comparing the patterns of retention of the imprinted compounds on the different MIPs when related to a blank (non‐imprinted) polymer in a high performance liquid chromatography system. Furthermore, frontal analysis was carried out on three polymers: a blank, a pyridine‐imprinted and a 4,4′‐bipyridyl‐imprinted polymer, to evaluate the number (Bt), average specificity and strength (dissociation constant; Kdiss) of the recognition sites. The Kdiss values of pyridine on the different polymers were in the range 0.10–0.12 M, and the amount of imprinted binding sites (Bt) 0.10–0.12 mmol/g. Kdiss values of 4,4′‐bipyridyl were approximately 0.06 M, with Bt values equal to the above, except for in the anti‐4,4′‐bipyridyl polymer where the Kdiss was determined to be 0.02 M and Bt 0.07 mmol/g. From the results it can be concluded that multiple additive weak interactions dominate the recognition of the template molecules in these imprinted polymers.

THE RATIONAL USE OF HYDROPHOBIC EFFECT-BASED RECOGNITION IN MOLECULARLY IMPRINTED POLYMERS

A novel molecularly imprinted polymer (MIP) system selective for D‐phenylalanine is described where polymerization is performed in aqueous solution. The unique polymer system comprises a hydrophobic moiety‐selective functional monomer, polymerizable β‐cyclodextrin, an electrostatic interacting functional monomer, 2‐acryloylamido‐2‐methylpropane sulfonic acid (AMPSA), and the crosslinking agent N,N′‐diacryloylpiperazine. Chromatographic evaluation of polymer–ligand recognition characteristics demonstrated ligand selectivity by the MIP and that optimal recognition was achieved through a balance of hydrophobic and electrostatic ligand–polymer interactions, indicating that recognition in these systems is regulated by enthalpy–entropy compensation. The imprinting effect was shown to be sufficient to reverse the inherent selectivity of cyclodextrin for L‐phenylalanine. Copyright

The Stroop effect on the internet

The classical Stroop color-naming task was converted to a Web administered version and tested against a conventional computerized version. In the first experiment, 20 male and 20 female participants were tested individually on both Stroop versions in random order. Both versions resulted in strong Stroop effects, but response times were slower overall for the Web-Stroop. A second experiment with 28 participants showed that the test results on the Web-Stroop could be replicated in a less controlled experimental setting, for example in the participants own home. In conclusion, findings suggest that administration of the Stroop color-naming test, and response time measurement in milliseconds on a personal computer, is possible via the Internet.

The α-defensin salt-bridge induces backbone stability to facilitate folding and confer proteolytic resistance.

Salt-bridge interactions between acidic and basic amino acids contribute to the structural stability of proteins and to protein–protein interactions. A conserved salt-bridge is a canonical feature of the α-defensin antimicrobial peptide family, but the role of this common structural element has not been fully elucidated. We have investigated mouse Paneth cell α-defensin cryptdin-4 (Crp4) and peptide variants with mutations at Arg7 or Glu15 residue positions to disrupt the salt-bridge and assess the consequences on Crp4 structure, function, and stability. NMR analyses showed that both (R7G)-Crp4 and (E15G)-Crp4 adopt native-like structures, evidence of fold plasticity that allows peptides to reshuffle side chains and stabilize the structure in the absence of the salt-bridge. In contrast, introduction of a large hydrophobic side chain at position 15, as in (E15L)-Crp4 cannot be accommodated in the context of the Crp4 primary structure. Regardless of which side of the salt-bridge was mutated, salt-bridge variants retained bactericidal peptide activity with differential microbicidal effects against certain bacterial cell targets, confirming that the salt-bridge does not determine bactericidal activity per se. The increased structural flexibility induced by salt-bridge disruption enhanced peptide sensitivity to proteolysis. Although sensitivity to proteolysis by MMP7 was unaffected by most Arg7 and Glu15 substitutions, every salt-bridge variant was degraded extensively by trypsin. Moreover, the salt-bridge facilitates adoption of the characteristic α-defensin fold as shown by the impaired in vitro refolding of (E15D)-proCrp4, the most conservative salt-bridge disrupting replacement. In Crp4, therefore, the canonical α-defensin salt-bridge facilitates adoption of the characteristic α-defensin fold, which decreases structural flexibility and confers resistance to degradation by proteinases.

Crown ethers as a tool for the preparation of molecularly imprinted polymers.

Molecularly imprinted polymers have been prepared against aniline and a bis‐aniline compound, making use of a crown ether (18‐crown‐6) to solubilize the monomer–template complexes. Subsequent chromatographic rebinding studies in the absence of crown ether revealed regioselectivity for the templates in the respective polymers. This study indicates that crown ethers can be potentially useful in conjunction with molecular imprinting to solubilize and imprint organic solvent‐insoluble compounds. Copyright