Topological Charge-Transfer Indices: From Small Molecules to Proteins

Francisco      Torrens; Gloria      Castellano

Abstract

Valence-topological charge-transfer indices are applied to the calculation of dipole moment-pH at the isoelectric point. Dipole moments calculated by algebraic-vector semisums of charge-transfer indices are defined. The ability of indices, for the description of molecular charge distribution, is established by comparing them with the dipole moment of the valence-isoelectronic series of cyclopentadiene-benzene-styrene. Both charge-transfer indices are proposed: vector semisums μvec-μvec V. The μvec V is intermediate between μvec and μexperiment. The steric effect is almost constant along series and the dominating effect is electronic. The indices are applied to the calculation of the dipole moments of the homologous series of percutaneous enhancers and the isoelectric point of 21 amino acids. In most fits no superimposition of the corresponding Gk-Jk/Gk VJk V pairs is observed, which diminishes the risk of collinearity. The inclusion of heteroatoms in the π-electron systems is beneficial for the description of isoelectric point, because of either the role of additional p-orbitals provided by heteroatom or the role of steric factors in the π-electron conjugation. The use of (valence) chargetransfer indices gives limited results for amino-acid isoelectric points. The inclusion of the number of acidic/basic groups improves the models, especially for amino acids with more than two functional groups. The fitting line for 21 amino acids is used to estimate the lysozyme isoelectric point by replacing (1+Δn/nT) with (M+Δn)/nT. The lysozyme fragment results can estimate the isoelectric point of the whole protein within 1-13% error.

Keywords: Charge distribution, dipole moment, valence-isoelectronic series, valence-topological charge-transfer index, isoelectric point, amino acid, protein, lysozyme