An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates

α-Tocopheryl succinate (α-TOS) is a very promising anticancer agent; however, the mechanism of its action and the role of the succinic moiety in biological activity still remains unclear. This paper, presents the first determination of the X-ray structure of α-TOS and 2,2,5,7,8-pentamethylchroman-6-...

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Main Authors: Piotr Wałejko, Łukasz Dobrzycki, Artur Ratkiewicz, Paweł Socha, Stanisław Witkowski, Michał K. Cyrański
Format: Article
Language:English
Published: Elsevier 2019-03-01
Series:Journal of Saudi Chemical Society
Online Access:http://www.sciencedirect.com/science/article/pii/S1319610318301029
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spelling doaj-c79e57fc65d94be1b3fee6509f92c41c2020-11-24T21:34:29ZengElsevierJournal of Saudi Chemical Society1319-61032019-03-01233365377An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinatesPiotr Wałejko0Łukasz Dobrzycki1Artur Ratkiewicz2Paweł Socha3Stanisław Witkowski4Michał K. Cyrański5University of Bialystok, Institute of Chemistry, Ciołkowskiego 1K, 15-245 Białystok, Poland; Corresponding author.University of Warsaw, Faculty of Chemistry, Czochralski Laboratory of Advanced Crystal Engineering, Zwirki i Wigury 101, 02-089 Warsaw, PolandUniversity of Bialystok, Institute of Chemistry, Ciołkowskiego 1K, 15-245 Białystok, PolandUniversity of Warsaw, Faculty of Chemistry, Czochralski Laboratory of Advanced Crystal Engineering, Zwirki i Wigury 101, 02-089 Warsaw, PolandUniversity of Bialystok, Institute of Chemistry, Ciołkowskiego 1K, 15-245 Białystok, PolandUniversity of Warsaw, Faculty of Chemistry, Czochralski Laboratory of Advanced Crystal Engineering, Zwirki i Wigury 101, 02-089 Warsaw, Polandα-Tocopheryl succinate (α-TOS) is a very promising anticancer agent; however, the mechanism of its action and the role of the succinic moiety in biological activity still remains unclear. This paper, presents the first determination of the X-ray structure of α-TOS and 2,2,5,7,8-pentamethylchroman-6-yl succinate (PMCS). The X-ray data indicated high out of planarity deformation of the aryl ring in the chroman-6-ol system. α-TOS and PMCS differed in angle θ value (28.4° vs. 21.5°, respectively) and in their heterocyclic ring conformations: 2-endo-3-exo in PMCS, and 2-endo-3-exo and 2-exo-3-endo in α-TOS. Due to their strong intermolecular hydrogen bonds, both succinates form cyclically repeated dimeric structures in well assembled crystal supramolecular structures.A population analysis of α-tocopherol (α-TOC), 2,2,5,7,8-pentamethylchroman-6-ol (PMC) and their acyl derivatives was performed at B3LYP/6-31G(d,p)/CPCM level of theory using a natural bond orbital (NBO) analysis within the Gaussian 09 program package. For all compounds, relaxed scans were performed along torsion angle γ, and for low-energy conformers the Fukui functions were calculated: electron donor (ƒ−(r)), electron acceptor (ƒ+(r)), free radical (ƒo(r)) and dual descriptor (ƒ2(r)).In general, the differences observed between α-TOC and its acyl derivative structures result from the non-bonding lone pair of the phenolic oxygen and its interaction with aromatic system π electrons. Keywords: α-Tocopheryl succinate, X-ray, Natural Bond Orbital, DFT calculation, Fukui functionhttp://www.sciencedirect.com/science/article/pii/S1319610318301029
collection DOAJ
language English
format Article
sources DOAJ
author Piotr Wałejko
Łukasz Dobrzycki
Artur Ratkiewicz
Paweł Socha
Stanisław Witkowski
Michał K. Cyrański
spellingShingle Piotr Wałejko
Łukasz Dobrzycki
Artur Ratkiewicz
Paweł Socha
Stanisław Witkowski
Michał K. Cyrański
An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
Journal of Saudi Chemical Society
author_facet Piotr Wałejko
Łukasz Dobrzycki
Artur Ratkiewicz
Paweł Socha
Stanisław Witkowski
Michał K. Cyrański
author_sort Piotr Wałejko
title An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
title_short An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
title_full An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
title_fullStr An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
title_full_unstemmed An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
title_sort x-ray and natural bond orbital (nbo) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates
publisher Elsevier
series Journal of Saudi Chemical Society
issn 1319-6103
publishDate 2019-03-01
description α-Tocopheryl succinate (α-TOS) is a very promising anticancer agent; however, the mechanism of its action and the role of the succinic moiety in biological activity still remains unclear. This paper, presents the first determination of the X-ray structure of α-TOS and 2,2,5,7,8-pentamethylchroman-6-yl succinate (PMCS). The X-ray data indicated high out of planarity deformation of the aryl ring in the chroman-6-ol system. α-TOS and PMCS differed in angle θ value (28.4° vs. 21.5°, respectively) and in their heterocyclic ring conformations: 2-endo-3-exo in PMCS, and 2-endo-3-exo and 2-exo-3-endo in α-TOS. Due to their strong intermolecular hydrogen bonds, both succinates form cyclically repeated dimeric structures in well assembled crystal supramolecular structures.A population analysis of α-tocopherol (α-TOC), 2,2,5,7,8-pentamethylchroman-6-ol (PMC) and their acyl derivatives was performed at B3LYP/6-31G(d,p)/CPCM level of theory using a natural bond orbital (NBO) analysis within the Gaussian 09 program package. For all compounds, relaxed scans were performed along torsion angle γ, and for low-energy conformers the Fukui functions were calculated: electron donor (ƒ−(r)), electron acceptor (ƒ+(r)), free radical (ƒo(r)) and dual descriptor (ƒ2(r)).In general, the differences observed between α-TOC and its acyl derivative structures result from the non-bonding lone pair of the phenolic oxygen and its interaction with aromatic system π electrons. Keywords: α-Tocopheryl succinate, X-ray, Natural Bond Orbital, DFT calculation, Fukui function
url http://www.sciencedirect.com/science/article/pii/S1319610318301029
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