Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics,thrombin and thermolysin inhibitors

Summary A relative comparison of the binding properties of different drug molecules requires their mutual superposition with respect to various alignment criteria. In order to validate the results of different alignment methods, the crystallographically observed binding geometries of ligands in the pocket of a common protein receptor have been used. The alignment function in the program SEAL that calculates the mutual superposition of molecules has been optimized with respect to these references. Across the reference data set, alignments could be produced that show mean rms deviations of approximately 1 Å compared to the experimental situation. For structures with obvious skeletal similarities a multiple-flexible fit, linking common pharmacophoric groups by virtual springs, has been incorporated into the molecular mechanics program MOMO. In order to combine conformational searching with comparative alignments, the optimized SEAL approach has been applied to sets of conformers generated by MIMUMBA, a program for conformational analysis. Multiple-flexible fits have been calculated for inhibitors of ergosterol biosynthesis. Sets of different thrombin and thermolysin inhibitors have been conformationally analyzed and subsequently aligned by a combined MIMUMBA/SEAL approach. Since for these examples crystallographic data on their mutual alignment are available, an objective assessment of the computed results could be performed. Among the generated conformers, one geometry could be selected for the thrombin and thermolysin inhibitors that approached reasonably well the experimentally observed alignment.     

Synthesis, band structure, and optical properties of Ba2ZnV2O8

A novel compound Ba₂ZnV₂O₈ has been synthesized in high temperature solution reaction and its crystal structure has been characterized by means of single crystal X-ray diffraction analysis. It crystallizes in monoclinic system and belongs to space group P2₁/c with a=7.9050(16), b=16.149(3), , β=90.49(3). It builds up from 1-D branchy chains of [ZnV₂O₈⁴⁻]_∞, and the Ba²⁺ cations are located in the space among these chains. The IR spectrum, ultraviolet-visible diffuse reflection integral spectrum and fluorescent spectra of this compound have been investigated. The calculated results of energy band structure by the density functional theory method show that the solid-state compound of Ba₂ZnV₂O₈ is an insulator with direct band gap of 3.48 eV. The calculated total and partial density of states indicate that the top valence bands are contributions from the mixings of O-2p, V-3d, and Zn-3d states and low conduction bands mostly originate from unoccupied antibonding states between the V-3d and O-2p states. The V-O bonds are mostly covalence characters and Zn-O bonds are mostly ionic interactions, and the ionic interaction strength is stronger between the Ba-O than between the Zn-O. The refractive index of n_x, n_y, and n_z is estimated to be 1.7453, 1.7469, and 1.7126, respectively, at wavelength of 1060 nm for Ba₂ZnV₂O₈ crystal.     

Thermal analysis of polysiloxanes, aromatic polyimide and their blends

Low molecular weight poly(dimethylsiloxane) and poly(methylphenylsiloxane) were synthesized and blended with polyimide (PI) at its precursor poly(amic acid) stage. FTIR analysis has proven the retention of polysiloxanes in polyimide after the ultimate curing of blends. Differential scanning calorimetric analysis was performed on polysiloxanes to elucidate the structures present in polymers while thermogravimetric analysis (TGA) was performed on polysiloxanes, polyimide as well as their blends to evaluate the thermal stability and to analyze the effect of polysiloxane incorporation in blends. Blends have shown synergistic improvement as compared to neat polyimide.     

Synthesis and Stereochemistry of New Bis(1,3-Oxathian-2-yl) Derivatives: Epimerisation and Chair–Twist Equilibria

The synthesis and stereochemistry of some new bis(1,3-oxathian-2-yl) derivatives are reported. The conformational behavior of these compounds and the orientation of their substituents are deduced from the NMR spectra, from the X-ray crystal structures of two compounds and from the ab-initio level calculations. The epimerization of diastereoisomers and the chair ⇌ 22,5-twist equilibria were studied by variable temperature NMR.     

Study of metal-loaded activated charcoals for the separation and determination of selenium species by energy dispersive X-ray fluorescence analysis

Conversion of adsorption properties of activated charcoal (C^∗) by metal modification towards selenite, selenate and seleno-dl-methionine (Se-Met) was studied. Several metals were included in modification studies and also a procedure was developed for the separation and independent determination of microgram quantities of these selenium species in aqueous solution. Selenium species were collected one by one from the same sample solution onto collector material by adsorbing them directly or after complex formation onto different metal-loaded activated charcoals (MgC^∗ and FeC^∗). The mass of selenium in these collectors was measured directly by energy dispersive X-ray fluorescence spectrometry (EDXRF). Detection limits for all three selenium species were better than 6 μg corresponding to concentration of 60 μg/l with 0.100 l of initial sample volume.     

What crystals of small analogs are trying to tell us about cellulose structure

The molecular geometries from crystal structures of 23 small molecules such as cellobiose were reviewed and extrapolated to give model cellulose chains. Within a given model, all monosaccharide units and their linkages are identical so the models are regular helices. Despite fairly large ranges for the glycosidic linkage torsion angles and , 29° and 57°, respectively, there is little variation in the n and h parameters of the model helices. They are extended, with h values (the advance per residue along the helix axis) of 5.04–5.27 Å. Some models were slightly right-handed, with n values up to 2.12 residues per helix turn. Left-handed models were in the majority, and their n values were as large as –2.91. These results are consistent with known structures of cellulose and its derivatives. An exception comes from a heavily derivatized cellobiose molecule. It yields right-handed helices with n 4.5 and h 3 Å. Because one half turn of this helix reverses the direction of the chain in a compact region, the linkage geometry is a model for chain-folding. Other derivatives that are unable to form the O3O5 hydrogen bond gave left-handed helices. The puckering of the glucose rings was also surveyed. A number of rings in small molecule structures are puckered to a degree that is similar to the puckering determined for methyl cellotrioside, cellotetraose, cellulose I and cellulose II.     

A Theoretical Study on the Conductivity of Carbon Doped BNNT

From the changes in energy band, density of state (DOS) and electronic structure calculated by the DFT/B3LYP method, the conductivity of carbon doped boron‐nitride nanotube (BNNT), which is formed by C‐C bond substituting B‐N bond, was discussed. The results indicate that the substitution will strengthen the conductivity of the tube, and its semi‐conductivity might be adjusted by controlling the substitution.     

Theoretical study of reaction channels for the weakly bound complex systems created with HF,CO2, and various amines

This investigation conducted reaction channels of weakly bound complexes CO₂…HF, CO₂…HF…NH₃, CO₂…HF…NH₂CH₃, CO₂…HF…NH(CH₃)₂, and CO₂…HF…N(CH₃)₃ systems, using the Gaussian 98 package at the B3LYP/6‐311++G(3df,2pd) level. The syn‐fluoroformic acid or syn‐fluoroformic acid plus NH₃ or amine conformers are more stable than the related anti‐fluoroformic acid or anti‐fluoroformic acid plus NH₃ or amine conformers. However, the above‐mentioned weakly bound complexes are more stable than both the related syn‐ and anti‐type fluoroformic acid or acid plus NH₃ or amine conformers and their related decomposed into CO₂ + HF or CO₂ + NHR₃F (R?H, CH₃) combined molecular systems. Five reaction channels of the weakly bound complexes exist. Each channel includes weakly bound complexes and their related above‐mentioned systems. Moreover, each reaction channel contains two transition states. The transition state between the weakly bound complex and anti‐fluoroformic acid type structure (T₁₃) is significantly higher than that of internal rotation (T₂₃) between syn‐ and anti‐FCO₂H (or FCO₂H…NR₃) structures. However, the above‐mentioned T₁₃ can significantly decrease its energy by adding the third molecule NH₃ or NR₃ (R?H or CH₃). The more CH₃ that is substituted in NR₃ of the reaction channel, the lower the activation energy of the transition state in the system is affected. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Synthesis of a novel rigid molecule family for the investigation of electron and energy transfer

Three new rigid bridging ligands for metal complexation (7=bmb, 8=bqb and 11=btb) were prepared from a rigid triptycene spacer connected to two bipyridine ligands using a Horner–Emmons type reaction. The triptycene spacer is substituted by methoxy groups in the case of bmb and in the case of bqb by a benzoquinone substituent. The corresponding metal complexes (ruthenium and/or osmium) were synthesised and the different luminescence behaviour was tested. They show great potential for the investigation of intramolecular electron and energy transfer reactions. The dinuclear metal complex Ru---bqb---Os is an interesting system in which the bridging ligand bqb acts as a redox switch, able to tune the conductivity for energy or electrons across the bridge.