Temozolomide binding to Cucurbit[7]uril: QTAIM, NCI-RDG and NBO analyses
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ORIGINAL ARTICLE
Temozolomide binding to Cucurbit[7]uril: QTAIM, NCI‑RDG and NBO analyses Khawla Yahiaoui1,2 · Lynda Seridi1,2 · Karima Mansouri1,2 Received: 1 June 2020 / Accepted: 11 September 2020 © Springer Nature B.V. 2020
Abstract The inclusion behavior of antineoplastic Temozolomide (TMZ) in the cavitand host Cucurbit[7]uril (CB[7]), with 1:1 stoichiometry, was investigated in this research work. Structural and electronic studies were conducted in vacuum and water. We used the DFT/B3LYP and the dispersion corrected DFT-D/wB97X-D functionals with 6-31G(d), 6–31 + G(d) and 6-31 + G(d,p) basis sets. All methods agree on the 3D optimum structure, in which a total inclusion of TMZ in CB[7] cavity is observed. A destabilizing effect of solvation was highlighted and confirmed from Frontier Molecular Orbital and global reactivity descriptors analyses. Furthermore, The nature and strength of intermolecular interactions were studied using Natural Bond Orbital (NBO) and Quantum Theory of Atoms In Molecule (QTAIM) analyses. Both models corroborate on the overall conclusion revealing that the conventional N–H⋯O and improper C–H⋯O H-bonds are mainly the driving forces stabilizing TMZ@CB[7] complex. Also, in the framework of the topological QTAIM analysis, we classified these closed shell interactions and distinguished two kinds of H-bonds: with electrostatic character or partially covalent in nature. The analysis of Espinosa energies unveils a good correlation with the intermolecular bond distance and electron density. Moreover, The Non-Covalent Interactions Reduced Density Gradient (NCI-RDG) method was used to reveal and distinguish between weak interaction regions; in fact it segregates attractive (H-bonding), dispersive (VdW) and repulsive interactions. Finally, from 1H NMR and TD-DFT computations, we identified, the interaction sites and the electronic transitions responsible of UV–Vis absorption bands, respectively. The best reproduction of experimental spectra is achieved with the dispersion corrected wB97X-D and extended basis sets. Keywords Temozolomide · Cucurbit[7]uril · TD-DFT · NBO · QTAIM · NCI-RDG
Introduction DNA alkylating agents have historically played an important role in systemic chemotherapy for cancer [1]. In recent years, Temozolomide (Fig. 1a) with the IUPAC name 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d][1–3,5]tetrazine-8-carboxamide and general formula C6H6N6O2 has Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10847-020-01027-5) contains supplementary material, which is available to authorized users. * Lynda Seridi [email protected]; seridi.lynda@univ‑guelma.dz 1
Laboratoire de Physique de Guelma (LPG), Université 8 Mai 1945 Guelma, BP 401, 24000 Guelma, Algeria
Département de Génie des Procédés, Faculté des Sciences et de la Technologie, Université 8 Mai 1945 Guelma, BP 401, 24000 Guelma, Algeria
2
particularly attracted a great attention. It’s an orally administered alkylating agent of imidazotetrazine derivatives which has
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