Theoretical prediction of the polarity/polarizability parameter π2H

Ab initio and DFT calculations on the structure and properties of over 98 molecules are reported. Properties calculated for the molecules are assessed for their ability to correlate and predict experimentally derived values of the polarity/polarizability parameter, π. Using multivariate linear regression and partial least squares methods, four properties stand out as predictors of π: the molecular dipole moment, the polarizability, the CHelpG atomic charges and the frontier molecular orbital energies. These properties correlate π to close to the standard deviation in a previously published fragmental approach. The partial least squares method is shown to result in significantly better predictions for an external validation set.

[1]  R. S. Mulliken.  Electronic Population Analysis on LCAO–MO Molecular Wave Functions. I , 1955 .

[2]  J. Pople,et al.  Self‐Consistent Molecular‐Orbital Methods. IX. An Extended Gaussian‐Type Basis for Molecular‐Orbital Studies of Organic Molecules , 1971 .

[3]  P. A. Christiansen,et al.  Numerical coupled hartree-fock parallel polarizabilities for FH and CO , 1977 .

[4]  P. A. Christiansen,et al.  Gaussian basis sets for polarizability calculations , 1978 .

[5]  M. Abraham,et al.  Calculations on ionic solvation. Part 1.—Free energies of solvation of gaseous univalent ions using a one-layer continuum model , 1978 .

[6]  E. Grant,et al.  The dipole moments of 1,3-dimethylthiourea, 1,3-dimethyl-2-cyanoguanidine and 1,1-bis-methylamino-2-nitroethene in a aqueous solution , 1982 .

[7]  Bruce R. Kowalski,et al.  Chemometrics, mathematics and statistics in chemistry , 1984 .

[8]  Michael H. Abraham,et al.  Solubility properties in polymers and biological media. 4. Correlation of octanol/water partition coefficients with solvatochromic parameters , 1984 .

[9]  M. Abraham,et al.  The use of characteristic volumes to measure cavity terms in reversed phase liquid chromatography , 1987 .

[10]  M. Spackman.  Accurate prediction of static dipole polarizabilities with moderately sized basis sets , 1989 .

[11]  C. Breneman,et al.  Determining atom‐centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis , 1990 .

[12]  Michael H. Abraham,et al.  Hydrogen bonding: XVII. The characterisation of 24 gas-liquid chromatographic stationary phases studied by Poole and co-workers. including molten salts, and evaluation of solute-stationary phase interactions , 1991 .

[13]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[14]  Harpreet S. Chadha,et al.  Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain. , 1994, Journal of pharmaceutical sciences.

[15]  D. Y. Yoon,et al.  Conformational Characteristics of Dimethoxymethane Based upon ab Initio Electronic Structure Calculations , 1994 .

[16]  K. Viswanathan,et al.  Ab Initio Study of Trimethyl Phosphate: Conformational Analysis, Dipole Moments, Vibrational Frequencies, and Barriers for Conformer Interconversion , 1997 .

[17]  M. Abraham,et al.  Algorithms for Skin Permeability Using Hydrogen Bond Descriptors: the Problem of Steroids * , 1997, The Journal of pharmacy and pharmacology.

[18]  Daniel Svozil,et al.  Neural Network Prediction of the Solvatochromic Polarity/Polarizability Parameter PiH2[S_EL2;quad] , 1997, J. Chem. Inf. Comput. Sci..

[19]  Harpreet S. Chadha,et al.  Molecular Factors Influencing Drug Transfer across the Blood‐Brain Barrier , 1997, The Journal of pharmacy and pharmacology.

[20]  W. Cain,et al.  Draize Eye Scores and Eye Irritation Thresholds in Man Combined into one Quantitative Structure-Activity Relationship. , 1998, Toxicology in vitro : an international journal published in association with BIBRA.

[21]  Comparative study of hydrocarbon, fluorocarbon, and aromatic bonded RP-HPLC stationary phases by linear solvation energy relationships. , 1999 .

[22]  A. Leo,et al.  Correlation and estimation of gas-chloroform and water-chloroform partition coefficients by a linear free energy relationship method. , 1999, Journal of pharmaceutical sciences.

[23]  M. Abraham,et al.  Solute–solvent interactions in normal-phase liquid chromatography: a linear free-energy relationships study , 1999 .

[24]  Colin F. Poole,et al.  Classification of stationary phases and other materials by gas chromatography , 1999 .

[25]  James A. Platts,et al.  Estimation of Molecular Linear Free Energy Relation Descriptors Using a Group Contribution Approach , 1999, J. Chem. Inf. Comput. Sci..

[26]  James A. Platts,et al.  Estimation of Molecular Linear Free Energy Relationship Descriptors by a Group Contribution Approach. 2. Prediction of Partition Coefficients , 2000, J. Chem. Inf. Comput. Sci..