Linear and nonlinear optical properties of cumulenes and polyenynes: a model exact study

Model exact static and frequency-dependent polarizabilities, static second hyperpolarizabilities and THG coefficents of cumulenes and polyenynes, calculated within the correlated Pariser-Parr-Pople (PPP) model defined over the pi-framework are reported and compared with the results for the polyenes. It is found that for the same chain length, the polarizabilities and THG coefficients of the cumulenes are largest and those of the polyenynes smallest with the polyenes having an intermediate value. The optical gap of the infinite cumulene is lowest (0.75 eV) and is associated with a low transition dipole moment for an excitation involving transfer of an electron between the two orthogonal conjugated pi-systems. The polyenynes have the largest optical gap (4.37 eV), with the magnitude being nearly independent of the chain length. This excitation involves charge transfer between the conjugated bonds in the terminal triple bond. Chain length and frequency dependence of alpha(ij) and gamma(ijkl) of these systems are also reported. The effect of a heteroatom on the polarizability and THG coefficients of acetylenic systems is also reported. It has been found that the presence of the heteroatom reduces the polarizability and THG coefficients of these systems, an effect opposite to that found in the polyenes and cyanine dyes. This result has been associated with the different nature of the charge transfer in the acetylenic systems.

Functional interaction of diphenols with polyphenol oxidase - Molecular determinants of substrate/inhibitor specificity SO FEBS JOURNAL

Polyphenol oxidase (PPO) catalyzes the oxidation of o-diphenols to their respective quinones. The quinones autopolymerize to form dark pigments, an undesired effect. PPO is therefore the target for the development of antibrowning and antimelanization agents. A series of phenolic compounds experimentally evaluated for their binding affinity and inhibition constants were computationally docked to the active site of catechol oxidase. Docking studies suggested two distinct modes of binding, dividing the docked ligands into two groups. Remarkably, the first group corresponds to ligands determined to be substrates and the second group corresponds to reversible inhibitors. Analyses of the complexes provide structural explanations for correlating subtle changes in the position and nature of the substitutions on o-diphenols to their functional properties as substrates and inhibitors. Higher reaction rates and binding are reckoned by additional interactions of the substrates with key residues that line the hydrophobic cavity. The docking results suggest that inhibition of oxidation stems from an interaction between the aromatic carboxylic acid group and the apical His 109 of the four coordinates of the trigonal pyramidal coordination polyhedron of CuA. The spatial orientation of the hydroxyl in relation to the carboxylic group either allows a perfect fit in the substrate cavity, leading to inhibition, or because of a steric clash flips the molecule vertically, facilitating oxidation. This is the first study to explain, at the molecular level, the determinants Of substrate and inhibitor specificity of a catechol oxidase, thereby providing a platform for the design of selective inhibitors useful to both the food and pharmaceutical industries.

Antigenic determinants of human serum retinol binding protein as probed with monoclonal antibodies

Monoclonal antibodies raised against human serum retinol-binding protein (hRBP) were used as probes for the study of the antigenic determinants of hRBP and those shared with the same protein from other species. The antibodies could be classified into four distinct groups and react with the homologous proteins from the rat as well as the rabbit sera. Three of these antibodies recognize sequential or continuous epitopes while the remaining antibody is directed against a discontinuous or conformational epitope. By chemical cleavage with cyanogen bromide, the domains recognized by the monoclonal antibodies could be delineated. By solid-phase synthetic approach, the core sequences recognized by two of these monoclonal antibodies were identified to amino acid sequences 45–51 and 128–131 of the primary amino acid sequence of hRBP.

Mapping the common antigenic determinants in avidin and streptavidin

An epitope scan analysis of the whole sequence of avidin and core streptavidin using polyclonal antibodies to these two antigens reveal the presence of multiple common epitopes in both the proteins. These antigenic determinants consist mostly of either identical or similar residues. The antibody recognition sites in both antigens are shown to be localized to homologous regions.

Aerosol radiative forcing over land: effect of surface and cloud reflection

It is now clearly understood that atmospheric aerosols have a significant impact on climate due to their important role in modifying the incoming solar and outgoing infrared radiation. The question of whether aerosol cools (negative forcing) or warms (positive forcing) the planet depends on the relative dominance of absorbing aerosols. Recent investigations over the tropical Indian Ocean have shown that, irrespective of the comparatively small percentage contribution in optical depth (similar to11%), soot has an important role in the overall radiative forcing. However, when the amount of absorbing aerosols such as soot are significant, aerosol optical depth and chemical composition are not the only determinants of aerosol climate effects, but the altitude of the aerosol layer and the altitude and type of clouds are also important. In this paper, the aerosol forcing in the presence of clouds and the effect of different surface types (ocean, soil, vegetation, and different combinations of soil and vegetation) are examined based on model simulations, demonstrating that aerosol forcing changes sign from negative (cooling) to positive (warming) when reflection from below (either due to land or clouds) is high.

Structural analysis of dihydrofolate reductases enables rationalization of antifolate binding affinities and suggests repurposing possibilities

Antifolates are competitive inhibitors of dihydrofolate reductase ( DHFR), a conserved enzyme that is central to metabolism and widely targeted in pathogenic diseases, cancer and autoimmune disorders. Although most clinically used antifolates are known to be target specific, some display a fair degree of cross-reactivity with DHFRs from other species. A method that enables identification of determinants of affinity and specificity in target DHFRs from different species and provides guidelines for the design of antifolates is currently lacking. To address this, we first captured the potential druggable space of a DHFR in a substructure called the `supersite' and classified supersites of DHFRs from 56 species into 16 `site-types' based on pairwise structural similarity. Analysis of supersites across these site-types revealed that DHFRs exhibit varying extents of dissimilarity at structurally equivalent positions in and around the binding site. We were able to explain the pattern of affinities towards chemically diverse antifolates exhibited by DHFRs of different site-types based on these structural differences. We then generated an antifolate-DHFR network by mapping known high-affinity antifolates to their respective supersites and used this to identify antifolates that can be repurposed based on similarity between supersites or antifolates. Thus, we identified 177 human-specific and 458 pathogen-specific antifolates, a large number of which are supported by available experimental data. Thus, in the light of the clinical importance of DHFR, we present a novel approach to identifying differences in the druggable space of DHFRs that can be utilized for rational design of antifolates.