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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The influence of hydrogen bonding on partition coefficients

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Borges, Nadia Melo ; Kenny, Peter W. ; Montanari, Carlos A. ; Prokopczyk, Igor M. ; Ribeiro, Jean F. R. ; Rocha, Josmar R. ; Sartori, Geraldo Rodrigues
Total Authors: 7
Document type: Journal article
Source: Journal of Computer-Aided Molecular Design; v. 31, n. 2, p. 163-181, FEB 2017.
Web of Science Citations: 8

This Perspective explores how consideration of hydrogen bonding can be used to both predict and better understand partition coefficients. It is shown how polarity of both compounds and substructures can be estimated from measured alkane/water partition coefficients. When polarity is defined in this manner, hydrogen bond donors are typically less polar than hydrogen bond acceptors. Analysis of alkane/water partition coefficients in conjunction with molecular electrostatic potential calculations suggests that aromatic chloro substituents may be less lipophilic than is generally believed and that some of the effect of chloro-substitution stems from making the aromatic pi-cloud less available to hydrogen bond donors. Relationships between polarity and calculated hydrogen bond basicity are derived for aromatic nitrogen and carbonyl oxygen. Aligned hydrogen bond acceptors appear to present special challenges for prediction of alkane/water partition coefficients and this may reflect `frustration' of solvation resulting from overlapping hydration spheres. It is also shown how calculated hydrogen bond basicity can be used to model the effect of aromatic aza-substitution on octanol/water partition coefficients. (AU)

FAPESP's process: 13/18009-4 - Molecular design, synthesis and trypanocidal activity of cruzain reversible covalent inhibitors
Grantee:Carlos Alberto Montanari
Support type: Research Projects - Thematic Grants