Pose scoring by NMR

Recently, we have developed a fast approach to calculate NMR chemical shifts using the divide and conquer method at the semiempirical level. To demonstrate the utility of this approach for characterizing protein-ligand interactions, we used the deviation of calculated chemical shift perturbations from experiment to determine the orientation of a ligand (GPI-1046) in the binding pocket of the FK506 binding protein (FKBP12). Moreover, we were able to select the native state of the ligand from a collection of decoy poses. A key hydrogen bond between O1 and HN in Ile56 was also identified. Our results suggest that ligand-induced chemical shift perturbations can be used to refine protein/ligand structures.     

Pairwise decomposition of residue interaction energies using semiempirical quantum mechanical methods in studies of protein-ligand interaction

Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool that can increase our understanding of macromolecular recognition processes. Herein we calculate the pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCAII) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) using semiempirical quantum mechanics based methods. We dissect the interaction between the ligand and the protein by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution. In particular, the off-diagonal elements of the Fock matrix that is composed of the interaction between the ionic core and the valence electrons and the exchange energy between the subsystems or atoms of interest is examined in detail. Our analysis reveals that the fluorine-substituted benzylamine group of SBB does not directly affect the binding energy. Rather, we find that the strength of the interaction between Thr199 of HCAII and the sulfamylbenzoyl group of SBB affects the binding affinity between the protein and the ligand. These observations underline the importance of the sulfonamide group in binding affinity as shown by previous experiments (Maren, T. H.; Wiley: C. E. J. Med. Chem. 1968, 11, 228-232). Moreover, our calculations qualitatively agree with the structural aspects of these protein-ligand complexes as determined by X-ray crystallography.     

A facile one‐pot synthesis of novel substituted 1,2,3,4‐tetrahydropyrimidine,part 2: Synthesis of 1‐(aralkyl/aryl)‐3‐(alkyl/aralkyl/aryl)‐5‐aroyl‐1,2,3,4‐tetrahydropyrimidines

1‐(Aralkyl/aryl)‐3‐(alkyyaralkyl)‐5‐aroyl‐1,2,3,4‐tetrahydropyrimidines ( 2a‐c ) have been synthesized by dethiomethylation of 5‐aroyl‐6‐methylthio‐1,2,3,4‐tetrahydropyrimidines ( 1a‐c ). An alternative one‐pot synthetic strategy has been developed for the title compounds 2a‐t by the reaction of enaminones 3 with pri mary amine and formaldehyde in refluxing methanol in good yields.     

New products

Summary An efficient and economical GC method for rapid determination of FAMEs in rapeseed-mustard is described. The seeds were transmethylated with acetylchloride, using microwave heating and separation achieved on a 3 m column packed with a mixture of 2% SP-2300 and 3% SP-2310 on Chromosorb ‘W’. The method is compared with the conventional heating method and extended efficiently for half-seed analysis. The fatty acid composition of the FAMEs mixtures prepared by both methods was similar with highly significant correlation coefficients (P<0.001).     

Thermodynamic investigations of uranium-rich binary and ternary alloys

Uranium–zirconium, uranium niobium, and uranium–zirconium–niobium alloys were synthesized by the arc melting technique and their phase transition temperatures were determined using a high temperature calorimeter. Heat capacities of U–7 wt%Zr, U–7 wt%Nb, U–5 wt%Zr–2 wt%Nb, U–3.5 wt%Nb–3.5 wt%Zr, and U–2 wt%Zr–5 wt%Nb were measured using a differential scanning calorimeter in the temperature range 303–921 K. A set of self-consistent thermodynamic functions such as entropy, enthalpy, and Gibbs energy function data for these binary and ternary alloys were reported for the first time using heat capacity data obtained in this study and required literature data.     

Synthesis and characterization of a novel copolymer of glyoxal dihydrazone and glyoxal dihydrazone bis(dithiocarbamate) and application in heavy metal ion removal from water

We demonstrate synthesis of water insoluble, novel copolymer P_A1 from condensation of glyoxal dihydrazone and glyoxal dihydrazone bis(dithiocarbamate) monomers having high capacity to remove metal ions from aqueous solution. The presence of a high atomic percentage of nitrogen and sulfur atoms in P_A1 leads to strong ligating ability with metal ions. The monomers and the polymer have been characterized by FTIR, UV–Visible spectroscopy, CHNS elemental analysis, NMR, MALDI-MS, and TG/DTA. As a proof of concept, the P_A1 is tested for its ability to remove heavy metal ions Cu²⁺, Co²⁺, Fe²⁺, Ni²⁺, Mn²⁺, and CrO ₇ ^2? from aqueous solutions. P_A1 efficiently removed metals ions from the metal solutions. The highest absorption ability has been observed toward the iron salts where 0.969 g metal salt is absorbed by 1 g polymer. This study has implication for inexpensive and efficient polymer for purification of water.     

Association reaction between SiH3 and H2O2: a computational study of the reaction mechanism and kinetics

The association reaction between silyl radical (SiH₃) and H₂O₂ has been studied in detail using high-level composite ab initio CBS-QB3 and G4MP2 methods. The global hybrid meta-GGA M06 and M06-2X density functionals in conjunction with 6-311++G(d,p) basis set have also been applied. To understand the kinetics, variational transition-state theory calculation is performed on the first association step, and successive unimolecular reactions are subjected to Rice–Ramsperger–Kassel–Marcus calculations to predict the reaction rate constants and product branching ratios. The bimolecular rate constant for SiH₃–H₂O₂ association in the temperature range 250–600 K, k(T) = 6.89 × 10^?13 T ^?0.163exp(?0.22/RT) cm³ molecule^?1 s^?1 agrees well with the current literature. The OH production channel, which was experimentally found to be a minor one, is confirmed by the rate constants and branching ratios. Also, the correlation between our theoretical work and experimental literature is established. The production of SiO via secondary reactions is calculated to be one of the major reaction channels from highly stabilized adducts. The H-loss pathway, i.e., SiH₂(OH)₂ + H, is the major decomposition channel followed by secondary dissociation leading to SiO.