Noncovalent interactions transferability

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

The above examples show that proton transfer resulting in keto-enol tau-tomerism cannot be studied separately from the environment. The equilibrium between keto and enol forms, both in solution and in the solid state is a derivative of numerous noncovalent interactions that can stabilize a particular isomer. In this context, host-guest chemistry can shed more light towards understanding of the proton-transfer mechanism in biological systems. 

In an elegant self-assembling system based on the use of cyclodextrin hosts, DeCola and coworkers noncovalently linked an alkylcarboxyan-thracene to an a-cyclodextrin bearing Ru(II) complex that also had an Os(II) bipyridyl derivative attached via noncovalent interaction with a -cyclo-dextrin substituent on the Ru complex (Fig. 14). The system yields an energy transfer cascade from the photoexcited anthracene to the Ru to bpy 3 MLCT state, which in turn transfers energy to the Os(II) complex 3MLCT state. All rate constants are > 108 s-1 [88]. 

Chemists are well aware that strong molecular interactions may be accompanied by a flow of electron charge but the evidence they present has been disregarded by physicists. The latter consider this evidence not to represent legitimate noncovalent interactions, with the additional remark that in the case of very small electron transfers the polarization contribution is able to describe such small effects. 

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