Molecular structure-biological activity relationships on the basis of quantum-chemical calculations

Background: Pharmacological and physicochemical classification of bases’ selected analogues of nucleic acids is proposed in the study. Objective: Structural parameters received by the PCM (Polarizable Continuum Model) with several types of calculation methods for the structures in vacuo and in the aquatic environment together with the huge set of extra molecular descriptors obtained by the professional software and literature values of biological activity were used to search the relationships. Methods: Principal Component Analysis (PCA) together with Factor Analysis (FA) and Multiple Linear Regressions (MLR) as the types of the chemometric approach based on semi-empirical ab initio molecular modeling studies were performed. Results: The equations with statistically significant descriptors were proposed to demonstrate both the common and differentiating characteristics of the bases' analogues of nucleic acids based on the quantum chemical calculations and biological activity data. Conclusion: The obtained QSAR models can be used for predicting and explaining the activity of studied molecules.

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Synthesis of Bis(Carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 (n = 0, 1) and Attempt of Synthesis of Gadolinium Bis(Dicarbollide)

Molecules ◽

10.3390/molecules26051321 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1321

Author(s):

Yasunobu Asawa ◽

Aleksandra V. Arsent’eva ◽

Sergey A. Anufriev ◽

Alexei A. Anisimov ◽

Kyrill Yu. Suponitsky ◽

...

Keyword(s):

Molecular Structure ◽

Single Crystal ◽

Quantum Chemical Calculations ◽

Quantum Chemical ◽

X Ray Diffraction ◽

Stable Conformation ◽

Acyl Chlorides ◽

X Ray ◽

Cesium Fluoride ◽

The Stability

Bis(carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 (n = 0, 1) were prepared by the reactions of the corresponding carboranyl acyl chlorides with ethylenediamine. Crystal molecular structure of 1,1′-μ-(CH2NH(O)C-1,2-C2B10H11)2 was determined by single crystal X-ray diffraction. Treatment of bis(carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 with ammonium or cesium fluoride results in partial deboronation of the ortho-carborane cages to the nido-carborane ones with formation of [7,7′(8′)-μ-(CH2NH(O)C(CH2)n-7,8-C2B9H11)2]2−. The attempted reaction of [7,7′(8′)-μ-(CH2NH(O)CCH2-7,8-C2B9H11)2]2− with GdCl3 in 1,2-dimethoxy- ethane did not give the expected metallacarborane. The stability of different conformations of Gd-containing metallacarboranes has been estimated by quantum-chemical calculations using [3,3-μ-DME-3,3′-Gd(1,2-C2B9H11)2]− as a model. It was found that in the most stable conformation the CH groups of the dicarbollide ligands are in anti,anti-orientation with respect to the DME ligand, while any rotation of the dicarbollide ligand reduces the stability of the system. This makes it possible to rationalize the design of carborane ligands for the synthesis of gadolinium metallacarboranes on their base.

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