Metal (II) 3,4-dimetoksibenzoatın nikotinamid komplekslerinin Hirshfeld yüzey analizi, etkileşim enerjisi hesaplamaları ve in silico anti-SARS-CoV-2 potansiyelleri

Abstract

Bu çalışmada, kristal yapıları daha önce karakterize edilmiş olan metal (II) 3,4-dimetoksibenzoatın nikotinamid komplekslerinin moleküllerarası etkileşim türleri, moleküllerarası etkileşim enerjileri ve boşluk analizi CrystalExplorer programı (Versiyon 21.5) yardımıyla incelenmiştir. H…H, H…O/O…H, H…C/C…H, H…N/N…H, C…C, C…O/O…C, O…O ve C…N/N…C etkileşimleri, komplekslerin Hirshfeld yüzeyine katkıda bulunan moleküller arası etkileşimlerdir. Hesaplanan etkileşim enerjisi analizi sonuçlarına göre, toplam enerjiye en önemli katkıyı elektrostatik ve polarizasyon enerjileri sağlamaktadır. Çalışmada ayrıca, kompleks 1-3 ile SARS CoV-2'nin ana proteaz enzimi ve Omicron varyantının spike proteini arasındaki etkileşimler Moleküler docking çalışmaları ile incelenmiştir. Kompleks 1-3'ün, yükler arası çekim kuvvetleri, hidrojen bağı, elektrostatik ve hidrofobik etkileşimler yoluyla SARS-CoV-2'nin ana proteaz enzimi ve Omicron varyantının spike proteini ile etkileşime girdiği belirlenmiştir. Elde edilen sonuçlara göre özellikle kompleks 3 için ileri in vivo/in vitro çalışmalar önerilmektedir. Etkileşim enerjisi analizi ve moleküler docking çalışmaları sonucunda belirlenen sonuçlar komplekslerin yapısında bulunan hidrojen bağı donor akseptor gruplar vasıtasıyla oluşan hidrojen bağlarının gerek kristal paketin kararlılığına gerekse SARS CoV-2'nin önemli enzimlerini inhibe etmede önemli birer faktör olduğunu göstermektedir.

Keywords

• 3
• 4-Dimetoksibenzoik asit
• geçiş metal kompleksleri
• Hirshfeld yüzey analizi
• kovalent olmayan etkileşimler
• moleküler docking
• SARS CoV-2.

Hirshfeld surface analysis, interaction energy calculations and in silico anti-SARS-CoV-2 potentials of metal (II) 3,4-dimethoxybenzoate with nicotinamide complexes

Abstract

In this study, types of the intermolecular interactions, the intermolecular interaction energies, void analysis of diaquabis(3,4-dimethoxybenzoate)bis(nicotinamide)zinc(II) dihydrate (Complex 1), diaquabis(3,4-dimethoxybenzoate)bis(nicotinamide)nickel(II) dihydrate (Complex 2), diaquabis(3,4-dimethoxybenzoate)bis(nicotinamide)cobalt(II) dihydrate (Complex 3), whose crystal structures were characterized before, were investigated with the help of the CrystalExplorer program (Version 21.5). It has been determined that H…H, H…O/O…H, H…C/C…H, H…N/N…H, C…C, C…O/O…C, O…O, and C…N/N…C interactions are intermolecular interactions that contribute to the Hirshfeld surface of the complexes. According to the results of the interaction energy analysis calculated with the help of B3LYP/6-31G(d,p), B3LYP/6-31G(d), B3LYP/3-21G, HF/6-31G(d,p), HF/6-31G(d), HF/3-21G, DFT/6-31G(d,p), DFT/6-31G(d), DFT/3-21G, MP2/6-31G(d,p), MP2/6-31G(d), MP2/3-21G basis sets, the major amount of the total energy is contributed by electrostatic and polarization energies. The interactions between Complexes 1-3 and the main protease enzyme and the spike protein of Omicron variant of the SARS-CoV-2 were investigated by Molecular docking studies. It was determined that complexes 1-3 and the main protease enzyme and the spike protein of Omicron variant of the SARS-CoV-2 interact via attractive charges, hydrogen bonding, electrostatic contacts, and hydrophobic interactions. According to the obtained results, further in vivo/in vitro studies are recommended for complex 3. The results determined as a result of interaction energy analysis and molecular docking studies show that the hydrogen bonds formed by the hydrogen bond donor/acceptor groups in the structure of the complexes are an important factor in both the stability of the crystal package and inhibition of important enzymes of SARS CoV-2.

Keywords

• 3
• 4-Dimethoxybenzoic acid
• transition metal complexes
• Hirshfeld surface analysis
• non-covalent interactions
• molecular docking
• SARS CoV-2.

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