Fast calculation of quantum chemical molecular descriptors from the electronegativity equalization method.

The use of the Electronegativity Equalization Method (EEM) is presented for high performance calculation of molecular electrostatic descriptors, giving quite similar results to those obtained through Density Functional Theory (B3LYP/6-31G*) calculations. Molecular descriptors include atomic charges and different related descriptors as well as Fukui functions, hardness and softness.

Characterization of the interaction of 2-hydroxypropyl-beta-cyclodextrin with itraconazole at pH 2, 4, and 7.

Phase-solubility techniques were used to assess the effect of pH on itraconazole complexation with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). In addition, molecular modeling using beta-cyclodextrin as a surrogate for HPbetaCD was completed. Data suggested A(p)-type solubility relationships, indicating higher order complexation at higher HPbetaCD concentrations. Stability constants were derived from the solubility isotherms using a simplex optimization procedure. At pH 2 (2 units below the pK(a4)), a 1:2 complex formation was observed, whereas at pH 4 (i.e., the pK(a4) for itraconazole) and at pH 7, 1:3 complexation occurred. The lower order of complexation observed at lower pH may be related to substructure protonation which reduced HPbetaCD interaction. Molecular mechanics also suggest 1:3 complex formation for the neutral species, indicating that possible interaction sites may include (in order of binding) triazole > 1,4-diaminophenyl > 2-butyl approximate, equals piperazine.

Generate: a program for 3-D structure generation and conformational analysis of peptides and peptidomimetics.

The program Generate, aimed at generating 3-D structures for peptides and peptidomimetics, is presented. The algorithm is based on a build-up procedure, using a library of conformations of amino acid residues. This library is built from conformational analysis of amino acids placed in a di- or tripeptide environment to mimic the surroundings of the amino acid in a true peptide, considering different positions of the residue in the peptide chain (peptidyl fragment, NH(+)(3)-terminus or COO(-)-terminus). Cis-trans isomerism in the amide bonds is taken into account by construction of rotamer libraries for different isomers. Water solvation is included through the GB/SA model. New amino acid residues can easily be added to the libraries, making it possible to generate conformations of peptidomimetics.