Theoretical Study of the Role of Boron−Nitrogen Dative Bonds in the Physiological Action of Boronated Compounds

Abstract

Some boronated molecules have shown surprising physiological action; however, the mode of action of these compounds is not understood. Our hypothesis is that the boron moiety is attracted to Lewis base sites on an enzyme and the resulting interaction causes an inhibition of the physiological pathway. To study this problem, quantum mechanical calculations of boron−nitrogen bond dissociation energies for 12 molecules have been calculated and compared with physiological activities including anti-hyperlipidemic and anti-neoplastic behavior. Results of linear correlation analysis between bond dissociation energy and physiological action have shown evidence that our hypothesis has merit. Possible locations of enzyme inhibition by boronated compounds are inferred. In addition, structural and energetic features of boronated molecules, including intramolecular electrostatic interactions and Lewis acidity, are discussed.

Carbon monoxide formation from trimethylamine-boranecarboxylate: DFT studies of SNi and chelotropic mechanisms

“…In contrast, the hydrogen bonded waters decrease the chelotropic activation barrier (compare Fig. 1h, i and Table 1, lines 14,15). In this step the transition state is more polar than the starting carboxyborane anion, and thus the hydrogen bond become stronger and shorter.…”

“…Fisher et al studied several amine carboxyboranes, including TMA-BH 2 COOH, in an attempt to correlate the computed B-N dissociation energies with various physiological effects. 15 In several cases there was a negative correlation suggesting that a more facile B-N dissociation is associated with a greater physiological effect. The carboxylate forms of amine carboxyboranes were not studied.…”

“…Compounds containing the B-N dative bond have been the subject of a number of theoretical studies. [12][13][14][15][16][17] The studies have shown that accurate prediction of geometry and energy in this class of compounds requires the use of correlated ab initio theory such as MP2 or a recent density functional theory using an augmented and polarized basis set. Fisher et al studied several amine carboxyboranes, including TMA-BH 2 COOH, in an attempt to correlate the computed B-N dissociation energies with various physiological effects.…”

Isosteres of peptides: boron analogs as dipolar forms of α‐amino acids – a theoretical study

“…1 The simplest of the amine-borane complexes -NH 3 ÁBH 3 has been extensively investigated by both experimental and theoretical methods. [17][18][19] There are few reports on experimental and theoretical studies on 'aminecarboxy boranes' like NH 3 ÁBH 2 CO 2 H. 20 However, there are only limited literature reports of 'amine-carboxyboranes' that resemble peptides. The synthesis of these 'amine-carboxyboranes' is straight forward and has been reported in the literature.…”

MM3 parameterization for the BN dative bond

“…We have carried out studies 8,9 that suggest the transfer of a borane moiety from these small molecules to a protein Lewis base site may play a role in the observed physiological response. This hypothesis motivates the need to carry out calculations that involve protein-sized structures.…”