DFT-Based Investigation of the Electronic and Nonlinear Optical (NLO) Properties of Quercetin and Molecular Docking Analysis Against Leukemia Target Proteins (6QGK and 2O21)

Abstract

In this study, the structural, electronic, nonlinear optical (NLO), and biological properties of the naturally occurring flavonoid 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one (Quercetin) were comprehensively investigated using density functional theory (DFT) and molecular modeling methods. Quantum chemical calculations were performed through the optimization of the ground state geometry using the B3PW91 and B3LYP functionals and the 6-31G(d,p) basis set. The electronic structure, charge transfer dynamics, and chemical stability of the molecule were evaluated by calculating Mulliken atomic charge distributions, boundary molecular orbital (HOMO–LUMO) energies, and spherical reactivity parameters based on the optimized neutral molecular structure. Molecular electrostatic potential (MEP) analysis was used to map reactive centers and potential hydrogen bonding capacity against electrophilic and nucleophilic attacks. Furthermore, the nonlinear optical (NLO) responses of the molecule were investigated by calculating the dipole moment, mean polarizability, and first-order hyperpolarizability components. The findings showed that quercetin possesses a distinct intramolecular charge transfer character and could be a promising optoelectronic material candidate. To evaluate the antileukemic activity potential of the compound at the molecular level, molecular docking studies were conducted with target proteins (PDB ID: 6QGK and 2O21) that are critical in leukemia pathogenesis. Docking simulations revealed that quercetin assumes stable conformations in the active sites of target enzymes; exhibiting high binding affinity through specific hydrogen bonds, covalent interactions, and hydrophobic networks (Pi-Sigma, Pi-Alkyl). The obtained data indicate that quercetin is a candidate scaffold structure with high potential for both functional optoelectronic applications and the development of next-generation targeted therapeutic agents.

Keywords

• Quercetin
• DFT calculation
• HOMO-LUMO analysis
• NLO
• Moleculer docking

Kuersetinin Elektronik ve Doğrusal Olmayan Optik (NLO) Özelliklerinin DFT Tabanlı İncelenmesi ve Lösemi Hedef Proteinlerine (6QGK ve 2O21) Karşı Moleküler Doking Analizi

Abstract

Bu çalışmada, doğal bir flavonoid olan 2-(3,4-dihidroksifenil)-3,5,7-trihidroksi-4H-kromen-4-on (Kuersetin) molekülünün yapısal, elektronik, doğrusal olmayan optik (NLO) ve biyolojik özellikleri, yoğunluk fonksiyoneli teorisi (DFT) ve moleküler modelleme yöntemleri kullanılarak kapsamlı bir şekilde incelenmiştir. Kuantum kimyasal hesaplamalar, B3PW91 ve B3LYP fonksiyonelleri ile 6-31G(d,p) temel seti kullanılarak temel durum geometrisinin optimizasyonu üzerinden gerçekleştirilmiştir. Optimize edilmiş nötr moleküler yapı üzerinden Mulliken atomik yük dağılımları, sınır moleküler orbital (HOMO–LUMO) enerjileri ve küresel reaktivite parametreleri hesaplanarak molekülün elektronik yapısı, yük transfer dinamikleri ve kimyasal kararlılığı değerlendirilmiştir. Moleküler elektrostatik potansiyel (MEP) analizi ile elektrofilik ve nükleofilik saldırılara karşı reaktif merkezler ve potansiyel hidrojen bağı kapasitesi haritalandırılmıştır. Ayrıca, dipol moment, ortalama polarize edilebilirlik ve birinci dereceden hiperpolarize edilebilirlik bileşenleri hesaplanarak molekülün doğrusal olmayan optik (NLO) yanıtları incelenmiştir. Elde edilen bulgular, kuersetinin belirgin bir molekül içi yük transfer karakterine sahip olduğunu ve umut verici bir optoelektronik materyal adayı olabileceğini göstermiştir. Bileşiğin antilösemik aktivite potansiyelini moleküler düzeyde değerlendirmek amacıyla, lösemi patogenezinde kritik öneme sahip hedef proteinler (PDB ID: 6QGK ve 2O21) ile moleküler kenetlenme (docking) çalışmaları yürütülmüştür. Kenetlenme simülasyonları, kuersetinin hedef enzimlerin aktif bölgelerinde kararlı konformasyonlar aldığını; spesifik hidrojen bağları, kovalent etkileşimler ve hidrofobik ağlar (Pi-Sigma, Pi-Alkil) aracılığıyla yüksek bağlanma afinitesi sergilediğini ortaya koymuştur. Elde edilen veriler, kuersetinin hem fonksiyonel optoelektronik uygulamalar hem de hedefe yönelik yeni nesil terapötik ajanların geliştirilmesi açısından yüksek potansiyele sahip bir aday iskele yapı olduğunu göstermektedir.

Keywords

• Kuersetin
• DFT hesaplaması
• HOMO-LUMO analizi
• NLO
• Moleküler doking

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