The new dimeric copper(II) complex from anticancer drug cytosine arabinoside

Özge Güngör; Zeynep Demircioğlu; Ayşegül Gölcü

doi:10.1016/j.molstruc.2022.133826

The new dimeric copper(II) complex from anticancer drug cytosine arabinoside

Özge Güngör, Zeynep Demircioğlu, Ayşegül Gölcü^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

In this study, the new copper(II) based cytosine arabinoside (ara-C) analog was synthesized and characterized by analytical and spectroscopic methods. Especially the data obtained from FT-IR spectroscopy showed that ara-C coordinated with copper(II) ions through –C=O and -N_ring groups and formed a complex compound in a tetrahedral structure. The proposed structure of this dimeric copper(II) complex was defined as [Cu₂(ara-C)₂Cl₄]. Also, the ability of both compounds to bind to double helix fish sperm DNA (dsDNA) and the damage to the HeLa cell line was investigated. All theoretical chemical activity analyses (hardness and softness parameters, Fukui functions, net charges) of the ara-C and [Cu₂(ara-C)₂Cl₄] molecules were performed with DFT with mixed basis set including LANL2DZ for Cu atom and 6-311G(d,p) for carbon, oxygen, nitrogen, chlorine and hydrogen atoms with B3LYP functional was applied. The stability of the molecule arising from hyperconjugative interactions, charge delocalization was analyzed by using natural bond orbital analysis (NBO) for optimized structure of [Cu₂(ara-C)₂Cl₄]. Also, the interactions between the studied molecules (ara-C and [Cu₂(ara-C)₂Cl₄] with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method. Furthermore, the best binding sites of the DNA (PDB:1BNA) protein to the ligands (ara-C and [Cu₂(ara-C)₂Cl₄] were examined and the binding energies and interaction states were determined by molecular docking study.

Original language	English
Article number	133826
Journal	Journal of Molecular Structure
Volume	1270
DOIs	https://doi.org/10.1016/j.molstruc.2022.133826
Publication status	Published - 15 Dec 2022

Bibliographical note

Publisher Copyright:
© 2022

Funding

The authors would like to thank the support of the grant of Istanbul Technical University (Scientific Research Projects Unit) under THD-2022-43892 project. The authors wish to thank TUBITAK (Project No: 112T721, COST/CM1105), KSU (Project No: 2015/1-68YLS) for the financial support and Prof. Dr. İbrahim Demirtaş (Karatekin University, Chemistry Department) for cell culture studies. We are indebted to the High-Performance-Computing (HPC) Linux Cluster HorUS of University of Siegen for the computer time provided. The authors would like to thank the support of the grant of Istanbul Technical University (Scientific Research Projects Unit) under THD-2022-43892 project. The authors wish to thank TUBITAK (Project No: 112T721 , COST/CM1105 ), KSU (Project No: 2015/1-68YLS ) for the financial support and Prof. Dr. İbrahim Demirtaş (Karatekin University, Chemistry Department) for cell culture studies. We are indebted to the High-Performance-Computing (HPC) Linux Cluster HorUS of University of Siegen for the computer time provided.

Funders	Funder number
Kansas State University	2015/1-68YLS
Universität Siegen
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu	112T721, COST/CM1105
Istanbul Teknik Üniversitesi	THD-2022-43892

Keywords

Chemical activity
Cytosine arabinoside
DFT
DNA/ECT
The copper(II) complex

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molstruc.2022.133826

Cite this

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title = "The new dimeric copper(II) complex from anticancer drug cytosine arabinoside",

abstract = "In this study, the new copper(II) based cytosine arabinoside (ara-C) analog was synthesized and characterized by analytical and spectroscopic methods. Especially the data obtained from FT-IR spectroscopy showed that ara-C coordinated with copper(II) ions through –C=O and -Nring groups and formed a complex compound in a tetrahedral structure. The proposed structure of this dimeric copper(II) complex was defined as [Cu2(ara-C)2Cl4]. Also, the ability of both compounds to bind to double helix fish sperm DNA (dsDNA) and the damage to the HeLa cell line was investigated. All theoretical chemical activity analyses (hardness and softness parameters, Fukui functions, net charges) of the ara-C and [Cu2(ara-C)2Cl4] molecules were performed with DFT with mixed basis set including LANL2DZ for Cu atom and 6-311G(d,p) for carbon, oxygen, nitrogen, chlorine and hydrogen atoms with B3LYP functional was applied. The stability of the molecule arising from hyperconjugative interactions, charge delocalization was analyzed by using natural bond orbital analysis (NBO) for optimized structure of [Cu2(ara-C)2Cl4]. Also, the interactions between the studied molecules (ara-C and [Cu2(ara-C)2Cl4] with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method. Furthermore, the best binding sites of the DNA (PDB:1BNA) protein to the ligands (ara-C and [Cu2(ara-C)2Cl4] were examined and the binding energies and interaction states were determined by molecular docking study.",

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AU - Güngör, Özge

AU - Demircioğlu, Zeynep

AU - Gölcü, Ayşegül

PY - 2022/12/15

Y1 - 2022/12/15

N2 - In this study, the new copper(II) based cytosine arabinoside (ara-C) analog was synthesized and characterized by analytical and spectroscopic methods. Especially the data obtained from FT-IR spectroscopy showed that ara-C coordinated with copper(II) ions through –C=O and -Nring groups and formed a complex compound in a tetrahedral structure. The proposed structure of this dimeric copper(II) complex was defined as [Cu2(ara-C)2Cl4]. Also, the ability of both compounds to bind to double helix fish sperm DNA (dsDNA) and the damage to the HeLa cell line was investigated. All theoretical chemical activity analyses (hardness and softness parameters, Fukui functions, net charges) of the ara-C and [Cu2(ara-C)2Cl4] molecules were performed with DFT with mixed basis set including LANL2DZ for Cu atom and 6-311G(d,p) for carbon, oxygen, nitrogen, chlorine and hydrogen atoms with B3LYP functional was applied. The stability of the molecule arising from hyperconjugative interactions, charge delocalization was analyzed by using natural bond orbital analysis (NBO) for optimized structure of [Cu2(ara-C)2Cl4]. Also, the interactions between the studied molecules (ara-C and [Cu2(ara-C)2Cl4] with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method. Furthermore, the best binding sites of the DNA (PDB:1BNA) protein to the ligands (ara-C and [Cu2(ara-C)2Cl4] were examined and the binding energies and interaction states were determined by molecular docking study.

AB - In this study, the new copper(II) based cytosine arabinoside (ara-C) analog was synthesized and characterized by analytical and spectroscopic methods. Especially the data obtained from FT-IR spectroscopy showed that ara-C coordinated with copper(II) ions through –C=O and -Nring groups and formed a complex compound in a tetrahedral structure. The proposed structure of this dimeric copper(II) complex was defined as [Cu2(ara-C)2Cl4]. Also, the ability of both compounds to bind to double helix fish sperm DNA (dsDNA) and the damage to the HeLa cell line was investigated. All theoretical chemical activity analyses (hardness and softness parameters, Fukui functions, net charges) of the ara-C and [Cu2(ara-C)2Cl4] molecules were performed with DFT with mixed basis set including LANL2DZ for Cu atom and 6-311G(d,p) for carbon, oxygen, nitrogen, chlorine and hydrogen atoms with B3LYP functional was applied. The stability of the molecule arising from hyperconjugative interactions, charge delocalization was analyzed by using natural bond orbital analysis (NBO) for optimized structure of [Cu2(ara-C)2Cl4]. Also, the interactions between the studied molecules (ara-C and [Cu2(ara-C)2Cl4] with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method. Furthermore, the best binding sites of the DNA (PDB:1BNA) protein to the ligands (ara-C and [Cu2(ara-C)2Cl4] were examined and the binding energies and interaction states were determined by molecular docking study.

KW - Chemical activity

KW - Cytosine arabinoside

KW - DFT

KW - DNA/ECT

KW - The copper(II) complex

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DO - 10.1016/j.molstruc.2022.133826

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AN - SCOPUS:85135917916

SN - 0022-2860

VL - 1270

JO - Journal of Molecular Structure

JF - Journal of Molecular Structure

M1 - 133826

ER -

The new dimeric copper(II) complex from anticancer drug cytosine arabinoside

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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