The role of S-bond in tenoxicam keto–enolic tautomerization

The role of S-bond in tenoxicam keto–enolic tautomerization Full article

Journal

CrystEngComm
ISSN: 1466-8033

Output data

Year: 2019, Volume: 21, Number: 36, Pages: 5392-5401 Pages count : 10 DOI: 10.1039/C9CE00874H

Authors

Arkhipov Sergey G. ^1,2,3 , Sherin Peter S. ^1,4 , Kiryutin Alexey S. ^1,4 , Lazarenko Vladimir A. ⁵ , Tantardini Christian ⁶

Affiliations

1	Novosibirsk State University, Pirogova str. 2, 630090 Novosibirsk, Russian Federation
2	Boreskov Institute of Catalysis SB RAS, Prospekt Akademika Lavrentyeva, 5, 630090 Novosibirsk, Russian Federation
3	Institute of Solid State Chemistry and Mechanochemistry SB RAS, Kutateladze str. 18, 630128 Novosibirsk, Russian Federation
4	International Tomography Center, Institutskaya 3a, 630090 Novosibirsk, Russian Federation
5	National Research Center “Kurchatov Institute”, Akademika Kurchatova square 1, Moscow, Russian Federation
6	Center for Energy Science and Technology, Skoltech Skolkovo Institute of Science and Technology, Nobelya str. 3, 143026 Moscow, Russian Federation

A non-steroidal anti-inflammatory drug, 4-hydroxy-2-methyl-N-2-pyridyl-2H-thieno(2,3-e)-1,2-thiazine-3-carboxamide 1,1-dioxide, called tenoxicam (TXM), with important implications in cancer treatment, has a peculiarity with respect to other molecules from the oxicam family. TXM is predominantly found in the zwitterionic form (ZWC) within the crystal structures of pure compounds and their solvates; however, it can be present in the β-keto–enolic form (BKE) or β-diketone (BDK) form. To understand this phenomenon, the combined effects of environment (solvent) and intra-molecular non-covalent interactions on the TXM keto–enol tautomerization were investigated through a combined experimental and computational study. We found that the polarity of a solvent had a minor influence on the crystallization process; this allowed to us synthesize and solve six new solvates with TXM in the ZWC form. Careful investigation of the non-covalent interactions between the sulphur atom of thiophenyl moiety and oxygen of the carbonyl group (S-bond) through a computational approach with the natural bond orbital (NBO) theory has shown that TXM crystallization is modulated by the S-bond. This study further confirms the importance of the S-bond in the drug design; however, nowadays, it is still underestimated.

Arkhipov S.G. , Sherin P.S. , Kiryutin A.S. , Lazarenko V.A. , Tantardini C.
The role of S-bond in tenoxicam keto–enolic tautomerization
CrystEngComm. 2019. V.21. N36. P.5392-5401. DOI: 10.1039/C9CE00874H

Submitted:	Jun 5, 2019
Accepted:	Jul 10, 2019
Published online:	Jul 18, 2019

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