Let’s not forget tautomers

A compound exhibits tautomerism if it can be represented by two structures that are related by an intramolecular movement of hydrogen from one atom to another. The different tautomers of a molecule usually have different molecular fingerprints, hydrophobicities and pKa’s as well as different 3D shape and electrostatic properties; additionally, proteins frequently preferentially bind a tautomer that is present in low abundance in water. As a result, the proper treatment of molecules that can tautomerize, ~25% of a database, is a challenge for every aspect of computer-aided molecular design. Library design that focuses on molecular similarity or diversity might inadvertently include similar molecules that happen to be encoded as different tautomers. Physical property measurements might not establish the properties of individual tautomers with the result that algorithms based on these measurements may be less accurate for molecules that can tautomerize—this problem influences the accuracy of filtering for library design and also traditional QSAR. Any 2D or 3D QSAR analysis must involve the decision of if or how to adjust the observed Ki or IC50 for the tautomerization equilibria. QSARs and recursive partitioning methods also involve the decision as to which tautomer(s) to use to calculate the molecular descriptors. Docking virtual screening must involve the decision as to which tautomers to include in the docking and how to account for tautomerization in the scoring. All of these decisions are more difficult because there is no extensive database of measured tautomeric ratios in both water and non-aqueous solvents and there is no consensus as to the best computational method to calculate tautomeric ratios in different environments

Quantification of Push-Pull Character of Azo Dyes and a Basis for Their Evaluation as Potential Nonlinear Optical Materials

The push–pull character of a series of para-phenyl substituted isophorone chromophores has been quantified by the 13C chemical shift difference of the three conjugated partial Cdouble bond; length as m-dashC double bonds and the quotient of the occupations of both the bonding and anti-bonding orbitals of these Cdouble bond; length as m-dashC double bonds as well. The correlations of the two push–pull quantifying parameters, and to the corresponding bond lengths, strongly recommend View the MathML sourceπCC∗/πCdouble bond; length as m-dashC as the general parameter to estimate charge alternation and as a very useful indication of the molecular hyperpolarizabilities for NLO application of the compounds studied

NMR spectroscopic and theoretical structural study of 5-exo-methylene-substituted hydantoins

The H-1 and C-13 NMR spectra of a series of 3-phenyl-5-exo-methylene-substituted hydantoins were recorded and assigned unequivocally by the various methods of 1D and 2D NMR spectroscopy. Employing the NMR parameters thus obtained, the NOEs between the different protons within the molecules and the results of accompanying semiempirical (AM1 and PM3, respectively) and ab initio (3-21G*) quantum chemical calculations, the tautomerism, the acidity, the redox potentials, the stereochemistry and the electron density distribution of the hydantoins were studied, In addition, the X-ray crystallographic structure of compound 1r is given and compared with the spectroscopic results