Characterization by Potentiometric Procedures of the Stability Constants of the Binary and Ternary Complexes of Cu(II) and Duloxetine Drug with Amino Acids

Asma A Alothman,Amal M Al-Mohaimeed

doi:10.1155/2019/1064942

Abstract

Potentiometric titration method has been used to define stoichiometries and stability constants of ternary complexes of Cu(II) with duloxetine (D) and some selected amino acids (L). The protonation constants of the ligands and the stability constants of the binary and ternary complexes of Cu(II) with the ligands were calculated from the potentiometric data using the HYPERQUAD program. The formation constants of the complexes formed in aqueous solutions and their concentration distributions as a function of pH were evaluated at 25°C and ionic strength 0.10 mol·L−1NaNO3. Respective stabilities of ternary complexes have been determined compared with the corresponding binary complexes in terms ofΔlog Kand %R.S. values. A novel binary and ternary duloxetine (D) drug with glycine and its Cu(II) complexes has been synthesized and characterized by several spectroscopic methods. Electronic spectra and magnetic susceptibility measurements reveal square planar geometry for both complexes. The elemental analyses and mass spectral data have justified the [Cu(D)(Gly)] and [Cu(D)Cl(H2O)] composition of complexes, where D = duloxetine and Gly = glycine. The EPR spectra of Cu(II) complexes support the mononuclear structures. Thermal properties and decomposition kinetics of Cu(II) complexes are investigated.

Highlights

Drugs are naturally occurring or synthetic, which contain oxygen or sulfur or nitrogen atoms in their functional groups. ey form complexes with metal ions either initially or after metabolic changes in the body to form stable five- or six-membered rings. e ever-increasing importance of ternary complexes especially those involving ligands containing functional groups identical with those present in enzymes, namely, -COOH, - NH2, and -CONH, is obvious from the application of such complexes in many analytical and biological reactions [1]
Duloxetine (D) (Figure 1) is chemically 2(+)-(S)-N-methyl-(gamma)-(1-naphthyloxy)-2thiophenepropylamine. e metal complexes of drugs are found to be more potent than parent drugs [6,7,8,9]. e literature survey reveals that, over the last decade, there has been tremendous attention towards studies on metal complex formation using drugs as ligands [10,11,12,13]. e best known example of a small molecule metal-containing drug is cisplatin, chemically (cis-[PtCl2(NH3)2]. e anticancer activity of this complex arises due to the formation of another ternary complex in which two chloride ions are replaced by the N-7 guanines located adjacently on Journal of Chemistry the DNA of the cancer cell [14]
Potentiometric titration data were used for protonation coefficients of all ligands, and formation coefficients of binary complexes were investigated by similar experimental circumstances of temperature and ionic strength for screening of ternary complexes

Summary

Introduction

Drugs are naturally occurring or synthetic, which contain oxygen or sulfur or nitrogen atoms in their functional groups. ey form complexes with metal ions either initially or after metabolic changes in the body to form stable five- or six-membered rings. e ever-increasing importance of ternary complexes especially those involving ligands containing functional groups identical with those present in enzymes, namely, -COOH, - NH2, and -CONH, is obvious from the application of such complexes in many analytical and biological reactions [1]. E ever-increasing importance of ternary complexes especially those involving ligands containing functional groups identical with those present in enzymes, namely, -COOH, - NH2, and -CONH, is obvious from the application of such complexes in many analytical and biological reactions [1]. Metal(II), ternary complexes with nitrogen- and oxygen-donor ligands acknowledged ample attention newly, as they may show remarkably high stability [2,3,4]. It looks to be of substantial attention to demeanor numerous studies causing binary and ternary complexes of Cu(II) connecting the duloxetine drug (D) and certain amino acids. E literature survey reveals that, over the last decade, there has been tremendous attention towards studies on metal complex formation using drugs as ligands [10,11,12,13]. Duloxetine (D) (Figure 1) is chemically 2(+)-(S)-N-methyl-(gamma)-(1-naphthyloxy)-2thiophenepropylamine. e metal complexes of drugs are found to be more potent than parent drugs [6,7,8,9]. e literature survey reveals that, over the last decade, there has been tremendous attention towards studies on metal complex formation using drugs as ligands [10,11,12,13]. e best known example of a small molecule metal-containing drug is cisplatin (cis-DDP), chemically (cis-[PtCl2(NH3)2]. e anticancer activity of this complex arises due to the formation of another ternary complex in which two chloride ions are replaced by the N-7 guanines located adjacently on Journal of Chemistry

Methods

Results

Conclusion