Journal
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 59, Issue 5, Pages 2479-2486Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jcim.9b00140
Keywords
-
Categories
Funding
- Irish Research Council
Ask authors/readers for more resources
A theoretical study has been carried out at the M062X/6-311+ +G(d,p) computational level to search for a rationale on ligands' affinity toward alpha(2)-adrenoceptors by estimating the nature and strength of intra-molecular hydrogen bonds potentially formed (by means of the QTAIM and NBO approaches) as well as the degree of deviation from planarity that could be observed in some of the compounds. Four different families have been studied: thiophen-2-yl, 3-carboxylatethiophen-2-yl esters, 3-cyanothiophen-2-yl, and 2-thiazolyl guanidinium derivatives. In the case of the thiophen-2-yl guanidines not substituted in the 3 position, nonplanarity was always observed, whereas in the thiazole series, intramolecular hydrogen bonds were identified between the guanidinium and the thiazole ring forcing the systems to planarity. Regarding the carboxylic esters, two different rotamers were found: quasi planar and quasi-perpendicular systems with very similar energy. Both of these isomers can form different nets of intramolecular hydrogen bonds and other types of noncovalent interactions. Different physicochemical properties such as basicity, solubility, or lipophilicity were calculated for these systems, but no correlation to the degree of planarity was found. However, when comparing the alpha 2-ARs affinity with the planarity of the molecules, a trend appears in the thiophen-2-yl guanidinium series indicating that lack of planarity seems to be optimal for alpha 2-ARs engagement.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available