Direct calculation of the binding free energies of FKBP ligands

Direct calculations of the absolute free energies of binding for eight ligands to FKBP protein were performed using the Fujitsu BioServer massively parallel computer. Using the latest version of the general assisted model building with energy refinement (AMBER) force field for ligand model parameters and the Bennett acceptance ratio for computing free-energy differences, we obtained an excellent linear fit between the calculated and experimental binding free energies. The rms error from a linear fit is 0.4 kcal/mol for eight ligand complexes. In comparison with a previous study of the binding energies of these same eight ligand complexes, these results suggest that the use of improved model parameters can lead to more predictive binding estimates, and that these estimates can be obtained with significantly less computer time than previously thought. These findings make such direct methods more attractive for use in rational drug design.     

Conformations in dioctyl substituted polyfluorene: a combined theoretical and experimental Raman scattering study

The structural properties of polyfluorenes (PF) are extremely sensitive to the choice of functionalizing side chains. Dioctyl substituted PF (PF8) adopts metastable structures that depend upon the thermal history and choice of solvents used in film forming conditions. We present a detailed study of the changes in the backbone and side chain morphology in PF8, induced by the various crystallographic phases, using Raman scattering techniques. The vibrational frequencies and intensities of fluorene oligomers are calculated using hybrid density-functional theory with a 3-21G(*) basis set. The alkyl side chains are modeled as limiting conformations: all anti, anti-gauche-gauche, and end gauche representations. The calculated vibrational spectra of single chain oligomers in conjunction with our experimental results demonstrate the beta phase, which is known to originate in regions of enhanced chain planarity as a direct consequence of the alkyl side chain conformation.     

Ligational behaviour of two biologically active N−S donors towards cobalt(III), iron(III), iron(II) and rhodium(III)

Summary The chelating behaviour of two biologically active ligands, pyridine-2-carboxaldehyde(4-phenyl) thiosemicarbazone(L₁H) and pyridine-2-carboxaldehyde thiosemicarbazone(LH), towards Fe^III, Co^III, Fe^II and Rh^III has been investigated. The ligands act as tridentate N–N–S donors, resulting in the formation of bis-chelate complexes of the type M^III(A)₂X·nH₂O (A=L₁ or L; X=Cl, ClO₄; M=Co^III, Rh^III, Fe^III), Fe^II(L₁H)₂SO₄·2H₂O and Fe^II(L₁)₂·H₂O. Biological activity of the ligands and the metal complexes in the form ofin vitro antibacterial activities towardsE. coli has been evaluated and the possible reasons for enhancement of the activity of ligands on coordination to metal ion is discussed.     

Synthesis and characterization of stable thiazolylazo anion radical complexes of ruthenium(II)

Two stable thiazolylazo anion radical complexes of ruthenium(II), [Ru(L1^•−)(Cl)(CO)(PPh₃)₂] (1) and [Ru(L2^•−)(Cl)(CO)(PPh₃)₂] (2) (where L1 = 2′-Thiazolylazo-2-imidazole and L2 = 4-(2′-Thiazolylazo)-1-n-hexadecyloxy-naphthalene), have been synthesized and characterized by spectroscopic and electrochemical techniques. The radical nature of the complexes has been confirmed from their room temperature magnetic moments and X-band ESR spectra. The radical complexes display a moderately intense (ε ~ 10⁴ M⁻¹ cm⁻¹) and relatively broad band in 430–460 nm region. In the microcrystalline state, complexes (1) and (2) display strong ESR signals at g = 1.951 and g = 1.988, respectively. In CH₂Cl₂ solution, complexes (1) and (2) show a quasireversible one-electron response near −0.64 and −0.59 V, respectively, versus Ag/AgCl due to the radical redox couple [Ru^II(L)(Cl)(CO)(PPh₃)₂]/[Ru^II (L^•−)(Cl)(CO)(PPh₃)₂].     

Polarized Hessian covariant: Contribution to pattern formation in the Föppl–von Kármán shell equations

We analyze the structure of the Föppl–von Kármán shell equations of linear elastic shell theory using surface geometry and classical invariant theory. This equation describes the buckling of a thin shell subjected to a compressive load. In particular, we analyze the role of polarized Hessian covariant, also known as second transvectant, in linear elastic shell theory and its connection to minimal surfaces. We show how the terms of the Föppl–von Kármán equations related to in-plane stretching can be linearized using the hodograph transform and relate this result to the integrability of the classical membrane equations. Finally, we study the effect of the nonlinear second transvectant term in the Föppl–von Kármán equations on the buckling configurations of cylinders.     

Topological alterations in human spermatozoa associated with the polyelectrolytic effect of RISUG

A new method of male contraception has been developed which results in long-term infertility and has the potential advantage of being reversible. The contraceptive, given the name RISUG (an acronym for Reversible Inhibition of Sperm Under Guidance) is a polyelectrolytic compound and when injected into the lumen of the vas deferens, induces a surface charge imbalance on the sperm membrane system leading to its destabilization. In the present study, morphological and topological alterations in human spermatozoa induced by RISUG have been investigated using atomic force microscopy (AFM). Complete disintegration of the plasma membrane with subsequent rupture and dispersion of the acrosomal contents is observed on treatment with RISUG in vitro. Considerable damage to the midpiece region with significant clustering of the mitochondria and its fusion with the head region is also observed. These observations are in agreement with the significant increase in the volume of RISUG-treated sperm-head region. Topological alterations in the flagellar and midpiece region of RISUG-treated spermatozoa have also been studied.     

Bohmian trajectories for photons

The first examples of Bohmian trajectories for photons have been worked out for simple situations, using the Kemmer–Duffin–Harish-Chandra formalism.     

Micellar catalyzed redox reactions of bilirubin in CTAB medium. A pulse radiolysis study

The reaction of CO with bilirubin which is not detectable in homogeneous aqueous medium proceeds almost with diffusion controlled rate in CTAB micellar system. This could be explained on the basis of catalysis caused by the possible electrostatic surface potential of cationic CTAB Micelles. The rate constant for the oxidation of bilirubin by haloperoxyl radicals have been shown to increase with increasing solvent polarity. Although the polarity effect was small, it followed a trend in the expected direction. Micellar effect was not observed in the oxidation reactions when alcohol was present in high concentration. But a small increase in the rate constant was observed when alcohol concentration was lower. © 1994 John Wiley & Sons, Inc.     

Infra red quantum dot photolithography

CdS quantum dots were fabricated photolithographically on the surface and in the bulk of silica hydrogels, as well as on the surface of planar substrates. Silica hydrogels were prepared with a standard base-catalyzed route, and the solvent was exchanged with a cold aqueous solution of Cd(NO₃)₂, NH₄OH, thiourea, and a capping agent, e.g., 2-mercaptoethanol. The samples were then exposed to a focused infrared beam produced by a continuous-wave Nd:YAG laser. The precursors reacted upon heating, and CdS nanoparticles formed in the illuminated regions. Use of capping agents allowed to control the mean particle size, while focusing of the beam inside hydrogel monoliths generated nanoparticles in their bulk, but not at the surface. Planar substrates were patterned by illuminating a precursor solution spin-coated on the substrates. The average size of the CdS nanoparticles could be varied between about 1.5 and 4.5 nm by varying the type and the concentration of the capping agents.