Diamagnetic Zn(II) and Hg(II) Complexes with Fluconazole: Synthesis, Spectral Characterization and Biological Investigation

Introduction

Fungal strains that cause invasive infections have been posing a serious threat not only to human health all over the world but also to agriculture and the environment^1-3. The Aspergillus, Candida, Cryptococcus, and Pneumocystis species are primarily to blame for the annual mortality of 1.5 to 2 million people from fungal infections⁴. Patients with compromised immune systems, such as those who have received hematopoietic stem cells or solid organ transplants, and HIV-infected individuals are particularly vulnerable to these pathogens ⁵. Currently, fungal infections are treated with four classes of organic compounds categorized according to their mode of action: polyenes like amphotericin B and nystatin, azoles like caspofungin and micafungin, echinocandins like micafungin, and antimetabolites like 5-fluorocytosine⁶. Due to their broad-spectrum antifungal activity, superior efficacy, and acceptable toxicity profile, azoles are the most commonly used antifungal agents⁷. The enzymes (cytochrome P450) involved in the synthesis of ergosterol, a component of the fungal cell membrane, are inhibited by this class of antifungal agents^8,9. Fluconazole (fcz), a triazole that belongs to the first generation of azoles, was residential to treat infections caused by Candida, such as C. albicans, C. tropicalis, C. parapsilosis, and dermatophytes. In contrast, Aspergillus species or other hyphomycetes, C. krusei, and other hyphomycetes are naturally resistant to fluconazole, whereas C. glabrata occasionally exhibits reduced sensitivity. Additionally, the overuse of this antifungal agent has resulted in a rapid rise in the number of fluconazole-resistant strains¹⁰. Due to fluconazole’s limited antifungal spectrum, development of resistance, and other drawbacks, it is urgent to discover novel compounds that can address these issues.

Diamagnetic Zn(II) and Hg(II) metal complexes containing fluconazole (Fig.1) and thiocyanate ion as ligands will be synthesized and characterized spectrally using microwave assisted synthesis as the primary objectives of this investigation. The biological research is also the focus of the ligands and their complexes.

Experimental Method

Materials

Fluconazole, metal nitrate, and potassium thiocyanate (KSCN) were obtained from the Alfa Aaser Company and used as such. The utilized organic solvents, namely, The AnalaR-grade dimethyl sulfoxide (DMSO), dimethylformamide (DMF), methanol, and ethanol were utilized as-is without further purification.

Synthesis of Zn(II) complex

1g (3.33 mmol) of...