Hirshfeld Surface Analysis, Interaction Energies Calculations and Investigation of Interactions with Coronavirus Spike Protein by Molecular Docking Studies of Cobalt(II) 4-Fluoro- ve 4-Bromobenzoate Nicotinamide Complexes

Abstract

In this study, the intermolecular interactions of diaquabis(4 -fluorobenzoate)bis(nicotinamide) cobalt (II) and diaquabis(4 bromobenzoate)bis(nicotinamide) cobalt (II) complexes, whose crystal structures were previously determined, were determined by Hirshfeld Surface Analysis. Intermolecular interaction contribution percentages were obtained from two-dimensional fingerprint plots. The interaction energies of the complexes were determined using the B3LYP/6-31G and HF/3-21G basis sets with the help of CrystalExplorer program. Electrostatic potential maps of the complexes were created with the CrystalExplorer program using the HF/STO-3G base set. In addition, the interactions of the complexes with the Coronavirus Spike Protein and Spike protein-ACE2 catalytic binding site were investigated with the help of Molecular Docking. Predictions of the complexes' ADMET (adsorption, distribution, metabolism, excretion and toxicity) properties were made using SwissADME and ProTox-II online databases. According to the results of Hirshfeld surface analysis, There are intermolecular interactions such as H…H, H...C/C…H, H…O/O…H, F…H/H…F, H…Br/Br…H, C…C, C…O/O…C, C…N/N…C, F…O/O…F, N…F/F…N, H…N/N…H, C…Br/Br…C, O… Br/Br…O, N…Br/Br…N, Br…Br and N…N on the Hirshfeld surface of the complexes. It was determined that electrostatic and dispersion energies provided the greatest contribution to the total energies of Complexes 1 and 2. When the substrate effects of the complexes against the Spike protein of SARS-CoV-2 and the Spike protein and the ACE2 binding site were examined in silico, it was determined that they could exhibit antagonist effects against proteins through many interactions such as hydrogen bonding, carbon hydrogen bonding, π-π stacking, π-π T-shaped interactions, electrostatic interactions, halogen, π-cation, π-alkyl, amide-π interactions, and alkyl.

Keywords

• Non-covalent interactions
• Hirshfeld surface analysis
• Molecular Docking
• Sars-CoV-2
• carboxylate complexes

Kobalt(II) 4-Floro- ve 4-Bromobenzoat Nikotinamid Komplekslerinin Hirshfeld Yüzey Analizi, Etkileşim Enerjisi Hesaplamaları ve Koronavirüs Spike Proteini ile Etkileşimlerinin Moleküler Docking Çalışmaları ile İncelenmesi

Abstract

Bu çalışmada kristal yapıları önceki çalışmalarda belirlenmiş olan diaquabis(4-florobenzoat)bis(nikotinamid) kobalt (II) ve diaquabis(4-bromobenzoat)bis(nikotinamid) kobalt (II) komplekslerinin moleküller arası etkileşimleri Hirshfeld Yüzey Analizi ile belirlenmiştir. Moleküllerarası etkileşim katkı yüzdeleri iki boyutlu parmak izi grafiklerinden elde edilmiştir. Komplekslerin etkileşim enerjileri CrystalExplorer programı yardımıyla B3LYP/6-31G ve HF/3-21G temel setleri kullanarak belirlenmiştir. Komplekslerin elektrostatik potansiyel haritaları CrystalExplorer programı ile HF/STO-3G temel seti kullanarak oluşturulmuştur. Çalışmada ayrıca komplekslerin Koronavirüs Spike Proteini ve Spike protein ile ACE2 katalitik bağlanma bölgesindeki etkileşimleri Moleküler Docking yardımı ile incelenmiştir. Komplekslerin ADMET (adsorpsiyon, dağılım, metabolizma, atılım ve toksisite) özelliklerine ilişkin tahminler SwissADME ve ProTox-II çevrimiçi veritabanları kullanılarak yapılmıştır. Hirshfeld yüzey analizi sonuçlarına göre komplekslerin Hirshfeld yüzeyinde H…H, H...C/C…H, H…O/O…H, F…H/H…F, H…Br/Br…H, C…C, C…O/O…C, C…N/N…C, F…O/O…F, N…F/F…N, H…N/N…H, C…Br/Br…C, O…Br/Br…O, N…Br/Br…N, Br…Br ve N…N gibi moleküller arası etkileşimler tespit edilmiştir. Kompleks 1 ve 2’nin toplam enerjilerine en büyük katkıyı elektrostatik ve dispersiyon enerjilerinin sağladığı belirlenmiştir. Komplekslerin SARS-CoV-2’nin Spike proteini ve Spike protein ile ACE2 bağlanma bölgesine karşı substrat etkileri in siliko olarak incelendiğinde, hidrojen bağı, karbon-hidrojen bağı, π-π istiflenmesi, π-π T-şekilli etkileşimleri, elektrostatik etkileşimler, halojen, π-katyon, π-alkil, amid-π etkileşimleri ve alkil gibi birçok etkileşim vasıtasıyla proteinlere karşı antagonist etki sergileyebileceği tespit edilmiştir.

Keywords

• Kovalent olmayan etkileşimler
• Hirshfeld yüzey analizi
• Moleküler Docking
• Sars-CoV-2
• karboksilat kompleksleri

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