A fast empirical GAFF compatible partial atomic charge assignment scheme for modeling interactions of small molecules with biomolecular targets

We report here a new and fast approach [Transferable Partial Atomic Charge Model (TPACM4)-upto four bonds] for deriving the partial atomic charges of small molecules for use in protein/DNA-ligand docking and scoring. We have created a look-up table of 5302 atom types to cover the chemical space of C, H, O, N, S, P, F, Cl, and Br atoms in small molecules together with their quantum mechanical RESP fit charges. The atom types defined span diverse plausible chemical environments of each atom in a molecule. The partial charge on any atom in a given molecule is then assigned by a reference to the look-up table. We tested the sensitivity of the TPACM4 partial charges in estimates of hydrogen bond dimers energies, solvation free energies and protein-ligand binding free energies. An average error ±1.11 kcal/mol and a correlation coefficient of 0.90 is obtained in the calculated protein-ligand binding free energies vis-à-vis an RMS error of ±1.02 kcal/mol and a correlation coefficient of 0.92 obtained with RESP fit charges in comparison to experiment. Similar accuracies are realized in predictions of hydrogen bond energies and solvation free energies of small molecules. For a molecule containing 50-55 atoms, the method takes on the order of milliseconds on a single processor machine to assign partial atomic charges. The TPACM4 programme has been web-enabled and made freely accessible at http://www.scfbio-iitd.res.in/software/drugdesign/charge.jsp.     

Mesoscale Clusters in the Crystallisation of Organic Molecules

The early stages of the molecular self-assembly pathway leading to crystal nucleation have a significant influence on the properties and purity of organic materials. This mini review collates the work on organic mesoscale clusters and discusses their importance in nucleation processes, with a particular focus on their critical properties and susceptibility to sample treatment parameters. This is accomplished by a review of detection methods, including dynamic light scattering, nanoparticle tracking analysis, small angle X-ray scattering, and transmission electron microscopy. Considering the challenges associated with crystallisation of flexible and large-molecule active pharmaceutical ingredients, the dynamic nature of mesoscale clusters has the potential to expand the discovery of novel crystal forms. By collating literature on mesoscale clusters for organic molecules, a more comprehensive understanding of their role in nucleation will evolve and can guide further research efforts.     

Carbon-13 NMR spectra of some labdane diterpenoids

Carbon-13 signal assignments of the labdane diterpenoids phlogantholide-A, its diacetate and isophlogantholide-A are reported. The assignments of the ¹³C NMR signals of 14-deoxyandrographolide and its diacetate, made earlier, have now been confirmed by lanthanide shift studies on the former and also by ¹³C spectral studies on anhydroandrographolide diacetate and 14-deoxy-11,12-didehydroandrographolide diacetate.     

The Thermodynamic Excess Properties of Binary Mixtures: I. Hexanol-1 +o-Xylene

The Grunberg-Nissan type interaction parameters have been used to treat volumetric and viscometric excess function data. Calculations have been made easier by using the reduced excess functions. The composition and temperature dependencies of the interaction parameters were found to depend on the nature of the dominant constituent. Using the Eyring theory of viscosity and the ERAS model, the reduced excess viscosity was equated with the Gibbs energy of mixing. A two-term Guggenheim Polynomial was used to explain the composition dependence of the excess functions.     

Copper-free Sonogashira coupling of 2-chloroquinolines with phenyl acetylene and quick annulation to benzo[b][1,6]naphthyridine derivatives in aqueous ammonia

An efficient copper-free Sonogashira coupling of 2-chloroquinolines with phenyl acetylene to 2-ethynylquinolines is described. We further discussed the one pot facile annulation of 2-alkynylquinoline-3-carboxaldehydes to 3-phenylbenzo[b][1,6]naphthyridines in aqueous ammonia in excellent yield.     

An alternate route to the synthesis of imidazo[1,2‐a]quinolines using I2‐NaI reagent

A new and a facile route to the synthesis of imidazo[1,2‐a]quinolines has been described via iodocyclization reaction of 2‐allylaminoquinoline derivatives using I₂‐NaI reagent. J. Heterocyclic Chem., (2011).     

An improved stereoselective total synthesis of (R)-rugulactone

A novel route for the stereoselective total synthesis of (R)-rugulactone 1 has been developed, starting from substituted epoxide 4 and 3-phenylpropionaldehyde 5 employing Julia-Kocienski olefination as a key step to construct E-configured α,β-unsaturated keto-group. The overall yield of the synthesized rugulactone is 19.94% and is better than the reported methods.