The structural analysis and modelling of ring substituent effect for the ortho-derivatives of 1-hydroxynaphthalene-2-carboxanilides and 2-hydroxynaphthalene-1-carboxanilides

作者：Skorna Peter^*; Michalik Martin; Luke Vladimir; Klein Erik

来源：Journal of Molecular Structure, 2017, 1144: 473-481.

DOI：10.1016/j.molstruc.2017.05.069

• Substituent effect descriptor
• Hammett constant
• Biological activity
• Proton affinity
• Drug development

The quantum chemical OFT study of 1-hydroxynaphthalene-2-carboxanilide (A-H) and 2-hydroxynaphthalene-1-carboxanilide (B-H) and their selected ortho-derivatives (A-R, B-R) is presented. The structural analysis showed that the energetically preferred conformation is stabilized via the intramolecular hydrogen bonds occurring between the C=O center dot center dot center dot H-O1 of A-H molecule and C=O center dot center dot center dot H-O2 groups of B-H molecule. The A-R derivatives are practically planar, while the B-R derivatives are slightly distorted due to the spatial repulsion of hydrogen atoms. The conformation analysis of molecules with deprotonated hydroxyl group supports the concept of existence of two conformer types with respect to the -NH-CO- bridge orientation. Stabilization of the naphtholate moiety by a hydrogen bond to the amide -NH- group may allow the compound to cross the membrane to the extracellular space. The ortho substitution effect on the selected calculated properties was analyzed and the theoretical data were correlated with the substituent constants. For the B-R derivatives, the antitubercular activity concentrations were correlated and predicted by the calculated quantities.

• 出版日期2017-9-15