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Model solvent systems for QSAR. Part IV. The hydrogen bond acceptor behaviour of heterocycles
Author(s) -
Leahy David E.,
Morris Jeffrey J.,
Taylor Peter J.,
Wait Alan R.
Publication year - 1994
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.610071213
Subject(s) - chemistry , pyridazine , heteroatom , ring (chemistry) , quinoline , pyridine , solvent , acceptor , quantitative structure–activity relationship , hydrogen bond , computational chemistry , molecule , organic chemistry , stereochemistry , condensed matter physics , physics
An LSER analysis based on the partitioning of 15 proton acceptor heterocycles has succeeded in extracting Σβ values, but only at the cost of demonstrating solvent dependence for some of them. As noted by Abraham, the division lies between protic and aprotic organic phases. His observation that pyridine and quinoline are less effective acceptors when surrounded by solvent than in 1 : 1 association was confirmed, and possible reasons for this are discussed. Two other such cases are N ‐methylimidazole and pyridazine, both of which give lower Σβ values in octanol than in PGDP. For both, Σβ in PGDP is what would be expected on the basis of log K β . The value for pyridazine in octanol suggests that, here, the ‘α‐effect’ is no longer operative; it is possible that this result can be generalized to other such heterocycles. Elsewhere, the most remarkable finding is that, where there are two proton acceptor sites in one heterocyclic ring, Σβ is the simple unattenuated sum of the separate β f values. If this result is general, it leads to a very simple way of estimating Σβ for heterocycles by calculation where data are unavailable. Evidence was also found, in certain cases, for hydrogen bonding to the π‐donor heteroatom or the aromatic ring. The QSAR implications of these results are discussed.