Synthesis, characterization, molecular modeling and antibacterial assays of new Ag(I) complexes with biologically active ligands

Orientador: Pedro Paulo CorbiDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: Neste trabalho, são descritas a síntese e a caracterização de três complexos inéditos de prata com os ligantes L-butionina sulfoximina (BSO), ácido 2-tiazolidina carboxílico (2-TC) e ácido 4-tiazolidina carboxílico (4-TC). O complexo de prata com BSO foi caracterizado por um conjunto de análises químicas e espectroscópicas, a saber: análise elementar, análise térmica, espectroscopia na região do infravermelho (IV), espectroscopia Raman, espectroscopia de ressonância magnética no estado sólido de C (C-RMN), estudos por DFT e ensaios biológicos. Os complexos de prata(I) com 2-TC e 4-TC, por sua vez, foram caracterizados por análise elementar, análise térmica, espectroscopia na região do infravermelho (IV), espectroscopia de ressonância magnética no estado sólido de C-RMN e N-RMN, estudos por DFT e ensaios biológicos. O complexo de prata com BSO, [Ag2(BSO)], apresenta uma composição 2:1 metal/ligante, sendo que a coordenação do ligante a um dos átomos de prata ocorre através dos grupamentos amino e carboxilato, enquanto que a coordenação ao segundo átomo de prata ocorre através do nitrogênio da sulfoximina. Os complexos de prata com 2-TC e 4-TC também apresentam proporção 2:1 metal/ligante, com um átomo de prata coordenado através do nitrogênio e o segundo átomo de prata coordenado através do carboxilato. As análises biológicas revelaram que os complexos [Ag2(BSO)], [Ag2(2-TC)] e [Ag2(4-TC)] são efetivos sobre cepas patogênicas Gram-positivas de Staphylococcus aureus, e cepas Gram-negativas de Escherichia coli e Pseudomonas aeruginosaAbstract: This work deals with the synthesis and characterization of three new silver(I) complexes with the ligands Lbuthionine sulfoximine (BSO), thiazolidine-2 carboxylic acid (2-TC) and thiazolidine-4 carboxylic acid (4-TC). The silver complex with BSO was characterized by elemental and thermal analyses, infrared and Raman spectroscopies, C nuclear magnetic resonance in the solid-state (C-NMR), DFT studies and biological assays. The silver(I) complexes with 2-TC and 4-TC were characterized by elemental and thermal analyses, infrared spectroscopy, C and N nuclear magnetic resonance in the solid-state, DFT studies and biological assays. The silver-BSO complex, [Ag2(BSO)], presents a 2:1 metal/ligand ratio. One of the silver(I) ion was shown to be coordinated through the amine nitrogen atom and the oxygen of carboxylate, while the second ion was shown to be coordinated through the nitrogen atom of the sulfoximine group. The silver(I) complexes with 2-TC and 4-TC also presented a 2:1 metal/ligand ratio, and are coordinated by the nitrogen and the oxygen atom of the carboxylate group. The biological assays revealed that the [Ag2(BSO)], [Ag2(2-TC)] and [Ag2(4-TC)] complexes are active against Gram-positive pathogenic strains of Staphylococcus aureus and Gramnegative pathogenic strains of Escherichia coli and Pseudomonas aeruginosaMestradoQuimica InorganicaMestre em Químic

Complexos de cobre(II) com derivados do ácido nalidíxico : síntese, caracterização e ensaios antimicrobianos e antitumorais preliminares

Orientador: Pedro Paulo CorbiTese (doutorado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: Este trabalho trata da síntese e da caracterização da carbohidrazida (hzd) e as hidrazonas derivadas do ácido nalidíxico com as porções 1H-pirrol-2-ilmetilideno (hpyrr), 1H-imidazol-2-ilmetilideno (h2imi), 1H-imidazol-4-ilmetilideno (h4imi), piridin-2-ilmetilideno (h2py), piridin-3-ilmetilideno (h3py), piridin-4-ilmetilideno (h4py) e (2-hidroxifenil)metilideno (hsali) como também seus complexos de cobre(II). Os ligantes e os complexos foram caracterizados por análise elementar, espectrometria de massas (ESI-QTOF-MS) e espectroscopias no infravermelho, ultravioleta-visível (UV-Vis) ressonância magnética nuclear (RMN). As estruturas cristalinas de hzd, h2imi, hpyrr, h3py e os complexos de cobre(II) [Cu3(h2imi)2Cl4H2O], {[Cu1,5(h4imi)Cl(MeOH)]Cl?2MeOH}n e [Cu3(h2py)4(H2O)]4BF4?3H2O foram determinadas. As estruturas dos ligantes também foram otimizadas pelos métodos DFT. Os complexos e os ligantes livres tiveram suas atividades antimicrobianas avaliadas in vitro frente a cepas bacterianas Gram-positivas de S. aureus (ATCC 25923, BEC9393 e Rib1), Gram-negativas de E. coli (ATCC 129214 e ATCC 25922), P. aeruginosa ATCC 27853 e S. enterica ATCC 14028 como também frente às leveduras C. albicans ATCC 26790 e F. moniliforme ATCC 38159. Não foi observado atividade antimicrobiana nas condições testadas. As atividades antitumorais dos complexos foram avaliadas in vitro frente as células cancerosas de U-251 (glioma), MCF-7 (mama), NCI-ADR/RES (ovário multi-resistente), 786-0 (rim), NCI-H460 (pulmão), PC-3 (próstata), UACC-62 (melanoma), OVCAR-3 (ovário), HT29 (cólon) e K562 (leucemia) como também frente a uma célula não tumoral - HaCat (queratinócitos imortalizados). O complexo [Cu3(h2imi)2Cl4H2O], em especial, apresentou GI50 mais baixo frente a linhagem celular NCI-ADR/RES (1,0·10-3 mmol L-1) quando comparado à cisplatina (8,3·10-3 mmol L-1) e uma maior viabilidade celular dado que o valor GI50 frente a linhagem celular HaCat foi de 9,2·10-2 mmol L-1 para este complexo e 3,8·10-3 mmol L-1 para a cisplatinaAbstract: This work deals with the synthesis and characterization of carbohydrazide (hzd) and hydrazones derivatives of the nalidixic acid with the moieties 1H-pyrrol-2-ylmethylidene (hpyrr), 1H-imidazol-2-ylmethylidene (h2imi), 1H-imidazol-4-ylmethylidene (h4imi), pyridin-2-ylmethylidene (h2py), pyridin-3-ylmethylidene (h3py), pyridin-4-ylmethylidene (h4py) and (2-hydroxyphenyl)methylidene (hsali) as well as their copper(II) complexes. The ligands and the complexes were characterized by elemental and mass spectrometric (ESI-QTOF-MS) analyses, infrared (IR), ultraviolet-visible (UV-Vis) and nuclear magnetic resonance (NMR) spectroscopic measurements. Crystal structures of hzd, h2imi, hpyrr, h3py and the copper(II) complexes [Cu3(h2imi)2Cl4H2O], {[Cu1.5(h4imi)Cl(MeOH)]Cl?2MeOH}n and [Cu3(h2py)4(H2O)]4BF4?3H2O were determined. The structures of the ligands were also optimized using DFT methods. The complexes and the free ligands had their preliminary antimicrobial activities evaluated in vitro against Gram-positive bacteria S. aureus (ATCC 25923, BEC9393 and Rib1), Gram-negative bacteria E. coli (ATCC 129214 and ATCC 25922), P. aeruginosa ATCC 27853 and S. enterica ATCC 14028 as well as the yeasts C. albicans ATCC 26790 and F. moniliforme ATCC 38159. No antimicrobial activities were observed under the tested conditions. The antitumoral activities of the complexes were assayed in vitro against the cancer cell lines U-251 (glioma), MCF-7 (breast), NCI-ADR/RES (multi-drug resistant ovary), 786-0 (kidney), NCI-H460 (lung), PC-3 (prostate), UACC-62 (melanoma), OVCAR-3 (ovary), HT29 (colon) and K562 (leukemia) as well as a non-tumoral cell line - HaCat (immortalized keratinocytes). The [Cu3(h2imi)2Cl4H2O] complex, in special, presented lower GI50 for the NCI-ADR/RES cell line (1.0·10-3 mmol L-1) when compared to cisplatin (8.3·10-3 mmol L-1) and a greater cell viability since the GI50 for HaCat cell line were shown to be 9.2·10-2 mmol L-1 for the complex and 3.8·10-3 mmol L-1 for cisplatinDoutoradoQuimica InorganicaDoutor em Ciências140707/2013-1CNP

N,N′,N′′ versus N,N′,O imine-containing coordination motifs: ligand-directed synthesis of mononuclear and binuclear cuII compounds

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOIt is demonstrated here that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. The N,N′,N′′-donating imine ligand led to a mononuclear compound, namely di­chlorido­[N,N-dimethyl-N′-731015631567CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO140466/2014-2140707/2013-12015/ 25114-42015/20882-3The authors are grateful to Dr Déborah de Alencar Simoni, technician of the Institutional Single-Crystal XRD Facility, UNICAMP, Brazil, for the data collectio

N,N′,N′′ versus N,N′,O imine-containing coordination motifs: ligand-directed synthesis of mononuclear and binuclear CuII compounds

It is demonstrated here that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. The N,N′,N′′-donating imine ligand led to a mononuclear compound, namely dichlorido[N,N-dimethyl-N′-(pyridin-2-ylmethylidene)ethane-1,2-diamine]copper(II) monohydrate, [CuCl2(C10H15N3)]·H2O, 1, while the N,N′,O-donating imine ligand produced a binuclear metal complex, namely μ2-chlorido-dichlorido(μ2-2-{[2-(dimethylamino)ethyl]iminomethyl}phenolato)(N,N-dimethylethylenediamine)dicopper(II) 0.11-hydrate, [Cu2(C11H15N2O)Cl3(C4H12N2)]·0.11H2O, 2. The structure of 2 is a remarkable example of a binuclear copper(II) complex containing a single substituted 2-iminomethylphenolate ligand that has two copper(II) sites in square-pyramidal coordination

Coordination compounds against multi-drug resistant bacteria: a critical review

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorTrabalho de Conclusão de Curso (Graduação)In the effort to shed some light on the bacterial multiresistance problem and the lack of a dynamic approach able to overcome the drug innovation gap, coordination compounds arise as a very promissing source of potential antibacterials. Ubiquitously active against several biomolecular components of the bacterial cell, these potential therapeutics have presented low probability of resistance development . As adjuvants those compounds were shown to reverse bacterial resistance against certain antibacterial drug. Herein the readership will find both historically revelant and current developments of coordination compounds encompassing transition and post-transition metal complexes as well as metalloid-based molecules that have shown activity against resistant strains. Seeking to further stimulate drug development, pivotal information regarding virulence and resistance factors of nosocomial pathogenic bacteria can also be found as bullet statements.2023-09-2

A binuclear silver complex with L-buthionine sulfoximine: synthesis, spectroscopic characterization, DFT studies and antibacterial assays{

A binuclear silver(I) complex with the amino acid L-buthionine sulfoximine (BSO) of composition Ag 2 C 8 H 16 N 2 O 3 S was synthesized and characterized by chemical and spectroscopic measurements, and DFT (density functional theory) studies. Solid-state 13 C nuclear magnetic resonance (SSNMR) and infrared vibrational spectroscopy (IR) analyses indicate the coordination of the nitrogen and carboxylate groups of the amino acid moiety to one of the silver atoms, while coordination to the second silver atom occurs through the nitrogen of the sulfoximine group. ESI-QTOF-MS measurements show the maintenance of the binuclear structure in solution. DFT studies confirm the proposed structure as a minimum of the potential energy surfac