Synthesis and characterization of Cd(II) complexes with hydrazonyl-selenazoles and hydrazonyl-thiazoles

[S. Kokanović]

179 str.

Hemija - Opšta i neorganska hemija / Chemistry - General and Inorganic Chemistry

Jedna od najvećih pretnji javnom zdravlju širom sveta jeste antimikrobna rezistencija. Uprkos ovom rastućem riziku, proizvedeno je vrlo malo antibiotika sa novim mehanizmima dejstva, što dovodi do nedostatka antibiotika koji bi efikasno mogli lečiti infekcije izazvane patogenima. Stoga, javlja se hitna potreba za dizajnom i razvojem novih klasa jedinjenja. Hibridi na bazi privilegovanih struktura, kao što su piridin, hidrazon, tiazol i njegov izoster selenazol, su molekuli od kojih se očekuje izrazita biološka aktivnost koja se može poboljšati kompleksiranjem sa jonima metala. Jedinjenja bazirana na metalima postaju alternativa organskim molekulima jer imaju sposobnost da ubijaju patogene specifičnim načinima delovanja. U ovom radu je prikazana sinteza i strukturna karakterizacija 14 kompleksnih jedinjenja Cd(II) sa hidrazonil-selenazolima i njihovim sumpornim analozima. Dobijeno je 12 katjonskih i dva neutralna kompleksa. Ligandi su koordinovani za centralni jon metala tridentatno preko NNN donorskog seta atoma: piridinskog, iminskog i preko atoma azota iz selenazolovog, odnosno tiazolovog prstena. Odstupanje od pravilne oktaedarske geometrije uočeno je u svim kompleksima i može se pripisati ograničenjima koje nameće koordinacija liganada. Ispitana su termička svojstva svih sintetisanih kompleksa. Rezultati su pokazali da mehanizam degradacije zavisi od prirode rastvarača koji su prisutni u spoljašnjoj sferi kompleksnog jedinjenja. Eksperimentalno određene konstante stabilnosti kompleksa sa derivatima 2-formilpiridina ukazuju na njihovu stabilnost. Antimikrobna aktivnost liganada i kompleksa ispitana je na pet sojeva Grampozitivnih, pet sojeva Gram-negativnih bakterija, dva soja gljivica i jednom soju kvasca. Svi kompleksi Cd(II) značajno su aktivniji u odnosu na svoje prekursore. Kompleksi sa derivatima 2- formilpiridina pokazali su veću antibakterijsku aktivnost u odnosu na komplekse sa derivatima 2- benzoilpiridina. Posebno se izdvajaju kompleksi 1–S, 2–S, 1–Se, 2–Se, 6–S, čije su vrednosti minimalne inhibitorne koncentracije u nanomolarnom opsegu i koji su pokazali bolju aktivnost na svim ispitivanim bakterijskim sojevima u odnosu na antibiotik (eritromicin). Kod antifungalne aktivnosti uočen je suprotan trend. Svi kompleksi sa 2-benzoilpiridinskim derivatima pokazali su veću aktivnost. Antioksidativni potencijal jedinjenja ispitivan je pomoću dva eseja. U DPPH testu obezbojavanja 2,2-difenil-1-pikrilhidrazil radikala, svi katjonski kompleksi imaju izraženiju sposobnost uklanjanja slobodnih radikala u odnosu na korišćeni standard. Analizom rezultata dobijenih u ABTS testu  obezbojavanje 2,2-azino-bis(3-etilbenztiazolin-6-sulfonske kiseline), uočeno je da katjonski kompleksi koji u spoljašnjoj sferi imaju nitratne jone pokazuju dvostruko bolju aktivnost od askorbinske kiseline i troloksa.

One of the greatest threats to public health worldwide is antimicrobial resistance. Despite this growing risk, very few antibiotics with new mechanisms of action have been developed, leading to a shortage of antibiotics that can effectively treat infections caused by pathogens. Therefore, there is an urgent need for the design and development of new classes of compounds. Hybrids based on privileged structures such as pyridine, hydrazone, thiazole, and its isoster selenazole are molecules expected to exhibit significant biological activity, which can be further enhanced by complexation with metal ions. Metal-based compounds are becoming an alternative to organic molecules due to their ability to kill pathogens through specific modes of action. In this study, the synthesis and structural characterization of 14 complex Cd(II) compounds with hydrazonyl-selenazoles and their sulfur analogs are presented. Twelve cationic and two neutral complexes were obtained. The ligands were coordinated to the central metal ion tridentately through the NNN donor set of atoms: pyridine, imine, and nitrogen atoms from the selenazole or thiazole ring. Deviation from the ideal octahedral geometry was observed in all complexes and can be attributed to the constraints imposed by ligand coordination. The thermal properties of all synthesized complexes were investigated. The results showed that the degradation mechanism depends on the nature of the solvents present in the outer sphere of the complex compound. Experimentally determined stability constants of complexes with 2-formylpyridine derivatives indicate their stability. The antimicrobial activity of the ligands and complexes was tested on five Gram-positive bacterial strains, five Gram-negative strains, two fungal strains and one yeast strain. All Cd(II) complexes were significantly more active compared to their precursors. Complexes with 2-formylpyridine derivatives demonstrated superior antibacterial activity compared to those with 2-benzoylpyridine derivatives. Notably, complexes 1–S, 2–S, 1–Se, 2–Se and 6–S exhibited minimum inhibitory concentration values in the nanomolar range and showed better activity against all tested bacterial strains than the reference antibiotic (erythromycin). In contrast, an opposite trend was observed in antifungal activity, where all complexes with 2-benzoylpyridine derivatives showed higher efficacy. The antioxidant potential of the compounds was evaluated using two assays. In the DPPH (2,2- diphenyl-1-picrylhydrazyl) radical scavenging assay, all cationic complexes demonstrated a stronger radical scavenging ability compared to the standard. Analysis of the results obtained in the ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) decolorization assay revealed that cationic complexes containing nitrate ions in the outer sphere exhibited twice the activity of ascorbic acid and trolox.

kadmijum(II), hidrazonil-selenazoli, hidrazonil-tiazoli, kristalografska analiza, termička stabilnost, konstante stabilnosti, antimikrobna svojstva, antioksidativna svojstva.

cadmium(II), hydrazonyl-selenazoles, hydrazonyl-thiazoles, crystallographic analysis, thermal stability, stability constants, antimicrobial properties, antioxidant properties.

546.48‑386(043.3)

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