Molecular Recognition

Rapid advances in biosensors have recently been reported. This has been possible due to rapid growth in the development of new biomaterials such as conducting polymers, copolymers and sol gels etc and the reported improvements in sensing techniques. Biosensors are miniaturized devices employing biochemical molecular recognition as the basis for a selective analysis. The response generated as a result of biochemical reaction is detected by a transducer to give a signal (optical/electrical/thermal) that can be used with or without amplification for the estimation of the concentration of an analyte in a given test sample. Among the various biosensors, electrochemical sensors, especially amperometric biosensors presently hold a leading position.Due to specificity, portability, simplicity, high sensitivity, potential ability for real-time and on-site analysis coupled with the speed and low cost, biosensors have been projected to have applications in food analysis, environment control, clinical detection, drug and agriculture industries etc. Besides this, biosensors offer exciting opportunities for numerous decentralized clinical applications, ranging from emergency room screening, home self testing and alternative site testing, continuous and real-time in vivo monitoring. New generation of biosensors combining new bioreceptors with the ever-growing number of transducers is emerging. The present paper highlights some of the recent advances in the area of biosensors contributed by our laboratory.

Screening for potential ligands and docking them into the binding sites of proteins is one of the main tasks in computer-aided drug design. Despite the progress in computational power, it remains infeasible to model all the factors involved in molecular recognition, especially when screening databases of more than 100,000 compounds. While ligand flexibility is considered in most approaches, the model of the binding site is rather simplistic, with neither solvation nor induced complementary usually taken into consideration. We present results for screening different databases for HIV-1 protease ligands with our tool Slide, and investigate the extent to which binding-site conformation, solvation, and template representation generate bias. The results suggest a strategy for selecting the optimal binding-site conformation, for cases in which more than one independent structure is available, and selecting a representation of that binding site that yields reproducible results and the iden...

Immunosensors are affinity ligand-based biosensor solid-state devices in which the immunochemical reaction is coupled to a transducer. The fundamental basis of all immunosensors is the specificity of the molecular recognition of antigens by antibodies to form a stable complex. This is similar to the immunoassay methodology. Immunosensors can be categorized based on the detection principle applied. The main developments are electrochemical, optical, and microgravimetric immunosensors. In contrast to immunoassay, modern transducer technology enables the label-free detection and quantification of the immune complex. The analysis of trace substances in environmental science, pharmaceutical and food industries is a challenge since many of these applications demand a continuous monitoring mode. The use of immunosensors in these applications is most appropriate. Similarly, a series of clinical problems may be solved by continuous monitoring of certain analytes. Clinical chemists should take advantage of immunosensors in clinical diagnostics. There are many recent developments in the immunosensor field which have potential impacts. The future role of this technique in intralaboratory, as well as bedside testing, will become even more important as the clinical laboratory is faced with increasing pressure to contain costs.

Over 1450 references to original papers, reviews and monographs have herein been collected to document the development of molecular imprinting science and technology from the serendipitous discovery of Polyakov in 1931 to recent attempts to implement and understand the principles underlying the technique and its use in a range of application areas. In the presentation of the assembled references, a section presenting reviews and monographs covering the area is followed by papers dealing with fundamental aspects of molecular imprinting and the development of novel polymer formats. Thereafter, literature describing attempts to apply these polymeric materials to a range of application areas is presented. Copyright © 2006 John Wiley & Sons, Ltd.

Over 1450 references to original papers, reviews and monographs have herein been collected to document the development of molecular imprinting science and technology from the serendipitous discovery of Polyakov in 1931 to recent attempts to implement and understand the principles underlying the technique and its use in a range of application areas. In the presentation of the assembled references, a section presenting reviews and monographs covering the area is followed by papers dealing with fundamental aspects of molecular imprinting and the development of novel polymer formats. Thereafter, literature describing attempts to apply these polymeric materials to a range of application areas is presented. Copyright © 2006 John Wiley & Sons, Ltd.

This work deals with tautomeric transformations of uracil (Ura) and thymine (Thy) in their model complexes with the deprotonated carboxylic group. Essential changes in the UV spectra of the bases upon their interaction with NaAc, vanishing signals of both imino protons in (1)H NMR spectra, and a perceptible decrease in intensity of both IR bands, related to the stretching vibrations nu(C=O) of the carbonyl groups, imply involvement of enolic tautomers. Results of quantum chemical calculations of the double complexes of the Ura(Thy) tautomers with CH(3)COO(-) at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory proved to be incompatible with the spectral features: despite the fact that the complexes of the enolic tautomers are much closer in energy to the diketo ones as compared to isolated tautomers, the energy gap between them is such that in tautomeric equilibrium dominate diketo forms. Calculations of triple complexes of the type CH(3)COO(-):Ura(Thy) tautomer:Na(+), taking into account the effect of the Na(+) coordination with tautomers, show that three triple complexes formed by enolic tautomers appeared more stable than those formed by diketo ones. This makes the UV and (1)H NMR data understandable, but the high residual intensity of the nu(C=O) bands in the IR spectra remains unclear. At that ion, Na(+) itself was not able to disturb the tautomeric equilibrium in the coordination complexes of the type Ura(Thy) tautomer:Na(+). To evaluate the DMSO effect, the CPCM solvation model was applied to triple complexes of the Ura tautomers. It appeared that in the solution there is coexistence between the diketo and enolic tautomers in a ratio of 53%:47%. This makes possible reconciliation of our experimental data. The biological significance of high-energy tautomers of nucleotide bases is discussed.

Vitreous coatings can be used as a means for the corrosion protection of metals and alloys due to their excellent dielectric properties. Their use is of particular interest in the case of highly aggressive media (different pH levels, temperatures up to 600 °C). However, ceramic coatings exposed to aggressive agents and thermal cycles can experience devitrification and spalling problems, with the consequent loss of their protective properties.The present study uses the electrochemical impedance spectroscopy technique to characterize, in a non-destructive way, the appearance of surface defects induced by the effect of temperature and chemical attack on a vitreous enamel deposited on steel. By means of analysis of the impedance diagrams obtained, a relationship is established between the loss of the coating's protective properties and the mechanism by which the corrosion process takes place.

In recent years, considerable progress has been made in the areas of molecular recognition and surface analysis. These fields meet in the field of sensor development, where the interaction between molecules and a suitably modified surface is of utmost importance. Vibrational spectroscopy is quite useful in these areas of research, as it may reveal the processes taking place at a molecular level. This thesis describes a number of applications of vibrational spectroscopy in the analysis of molecular recognition of molecules in solution, and in the characterisation of self-assembled interfaces. The study of molecular recognition of halide ions by specific hosts is reflected in the chapters 3, 4 and 5. In chapter 3, a new method is proposed for the determination of association constants applying infrared spectroscopy in combination with multivariate regression. This technique was developed to overcome the sensitivity problems arising when strongly associating complexes are investigated ...

Computer modeling has been developed and widely applied in studying molecules of biological interest. The force field is the cornerstone of computer simulations, and many force fields have been developed and successfully applied in these simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms using a combination of quantum mechanics and molecular mechanics, and (b) studying macromolecular dynamics and interactions using molecular dynamics (MD) and free energy (FE) calculation methods. Enzyme catalysis involves forming and breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent interactions appear ubiquitously in biology, but here we confine ourselves to review only noncovalent interactions between protein and protein, protein and ligand, and protein and nucleic acids.

The synthesis of heterogeneous catalysts, exemplified by supported transition metals, is a field of investigation where a constant dialogue is taking place between the macroscopic level (industrial preparation procedures) and the molecular level (illustrated by a discussion of adsorption mechanisms during the metal deposition step). Interesting problems arising from the molecular view of catalyst preparation are, e.g., the possibility of interfacial molecular recognition on metal deposition, or the control of interfacial kinetics. Studies of the initial steps of supported catalysts preparation has practical significance because of memory effects: the final state of the working catalyst is still influenced by the conditions of initial deposition, as illustrated by the example of Pt-WO x /Al 2 O 3 .

Molecular docking is an invaluable tool in modern drug discovery. This review focuses on methodological developments relevant to the field of molecular docking. The forces important in molecular recognition are reviewed and followed by a discussion of how different scoring functions account for these forces. More recent applications of computational chemistry tools involve library design and database screening. Last, we summarize several critical methodological issues that must be addressed in future developments.