Metathetical reactions involving [Pd(C2,N-dmpa)(mu-Cl)]2 (1) and the appropriate halides/pseudohalides salts afforded cyclopalladated dimers of the type [Pd(C2,N-dmpa)(mu-X)]2 (dmpa = S(_ ) enantiomer of N,N-dimethyl-1-phenethylamine; {X = Cl (1) and N3 (2)}. Mononuclear compounds of general formulae [Pd(C2,N-dmpa)(X)(lut)] {X = Cl (1a) and N3 (2a)} were obtained by bridge-splitting reactions involving the corresponding [Pd(C2,N- dmpa)(mu-X)]2 with 2,6-lutidine (lut) in the 1:2 M ratio at room temperature. Both the cyclopalladated compounds were characterized by means of elemental analysis, FT-IR, Raman, 1H and 13C NMR spectroscopy. The anti -proliferative activity of the mononuclear compounds 1a -2a was evaluated towards human glioblastoma (U251 and T98G) and melanoma cell lines (HT144 and LB373) and their IC50 values determined between 1 and 6 mu M. In most cases, the cytotoxic effects of compounds 1a -2a showed to be similar to those of cisplatin (depending on the cell line), what is of utmost importance when considering treatment alternatives for these aggressive tumor types. Binding studies on the representative compound 2a towards ct-DNA, however, showed low or no affinity, suggesting that the observed cytotoxicity against the human cell lines may involve different mechanisms of action compared to that of the platinum-based chemotherapy drug. The ability of 1a to induce the inhibition of topoisomerase II alpha activity has also been investigated. These cyclopalladated compounds can be transported and distributed through the body by human serum albumin (HSA), as observed by competition and computational studies with the protein. These findings are very promising and have motivated further studies for the design of new and bioactive cyclopalladated compounds for future medicinal purposes.

The halido- alpha-bridge cleavage reactions between [Pd( C 2 ,N -tetrox)( mu-Cl)] 2 precursor (tetrox = E- alpha tetralone oxime) with phosphines, in 1:2 molar ratio, have afforded mononuclear cyclopalladated compounds of the type [PdCl( C 2 ,N -tetrox)(L)] { L = triphenylphosphine ( 1 ); tris(4-methylphenyl)phosphine ( 2 ); tris(4-fluorophenyl)phosphine ( 3 ) and tris(4-methoxyphenyl)phosphine ( 4 )}. The compounds have been characterized by elemental analyses, infrared (FT-IR) and 1 H, 13 C{ 1 H} and 31 P{ 1 H}-NMR spectroscopies. The molecular structure of 3 has been determined by single crystal X-ray diffraction (SC-XRD) and the Hirshfeld Surface calculation (HS) has been performed. The antiproliferative activity of compounds 1-4 has been evaluated against breast (MCF-7) and lung (A549) human cancer cells, and human lung fibroblast (MRC-5). All cyclopalladated compounds have been more active than cisplatin against MCF-7 cells, with IC 50 values ranging from 19 to 26 mu M. Binding experiments involving compound 3 with ct-DNA and human serum albumin (HSA) have been carried out using spectroscopic techniques. The interaction between compound 3 and HSA has been studied by means of molecular docking. (c) 2021 Elsevier B.V. All rights reserved.

This work describes the enzymatic inhibitory activity of four novel Pd(ii) complexes towards topoisomerase IIα and cathepsins B and L.In silicostudies agree well with the enhancedin vitrocathepsin B inhibition induced by compound4(58% at 10 μM).

Herein, a robust docking protocol was developed by using a low-cost workflow to highlight the modulation at ATPase domain from Human Topoisomerase-IIα (TOP2A) towards four novel Pd(II)-complexes bearing N,S-donor ligands. In vitro TOP2A inhibition assay confirmed the ability of them to prevent the enzyme functions into concentration ranging at 6.25-25μM. These results exhibited more effectivity than anticancer agent etoposide (35μM) and merbarone (40-50μM). The compounds were screened via Resazurin assay against MCF-7, MDA-MB-231 (Human breast), DU-145 (Human prostate), A549 (Human lung) and Cal27 (Human tongue) tumor cell lines revealing great cytotoxic effects, primarily to MCF-7 (IC50=1.81-4.46μM). As well, 1-4 exhibited their selectivity index (SI) higher than cisplatin against HEK-293 (human kidney) normal cells, at least 11.6-fold (SI1-4=1.4-5.0; SIcis=0.12). Further, Red Blood Cell hemolytic test suggested in vitro non-toxic character for compound 4, previously evaluated as the most effective TOP2A inhibitor.

1UFGD Univ Federal da Grande Dourados, Faculdade de Ciências Exatas e Tecnologia Departamento de Química, , P.O. Box 364, 79.804-970, Dourados – MS – Brazil. 2UNESP Univ Estadual Paulista, Instituto de Química de Araraquara Departamento de Química Geral e Inorgânica, P.O. Box 355, 14801-970, Araraquara – SP – Brazil. 3UNESP Univ Estadual Paulista, Faculdade de Ciências Farmacêuticas, 14800-903, Araraquara – SP – Brazil. 4UTFPR Univ Tecnológica Federal do Paraná Departamento de Química, P.O. Box 135, 86036-370, Londrina – PR – Brazil. 5 UNIFAL -Univ Federal de Alfenas Instituto de Química, 37130-000, Alfenas – MG – Brazil.

Bridge splitting reactions between [Pd(C2,N-dmba)(μ-X)]2 (dmba = N,N-dimethylbenzylamine; X = Cl, I, N3, NCO) and 2,6-lutidine (lut) in the 1:2 molar ratio at room temperature afforded cyclopalladated compounds of general formulae [Pd(C2,N-dmba)(X)(lut)] {X = Cl- (1), I-(2), NNN-(3), NCO-(4)}, which were characterized by elemental analyses and infrared (IR), 1H NMR spectroscopy. The molecular structures of all synthesized palladacycles have been solved by single-crystal X-ray crystallography. The cytotoxicity of the cyclopalladated compounds has been evaluated against a panel of murine {mammary carcinoma (4T1) and melanoma (B16F10-Nex2)} and human {melanoma (A2058, SK-MEL-110 and SK-MEL-5) tumor cell lines. All complexes were about 10 to 100-fold more active than cisplatin, depending on the tested tumor cell line. For comparison purposes, the cytotoxic effects of 1-4 towards human lung fibroblasts (MRC-5) have also been tested. The late apoptosis-inducing properties of 1-4 compounds in SK-MEL-5 cells were verified 24 h incubation using annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide (PI). The binding properties of the model compound 1 on human serum albumin (HSA) and calf thymus DNA (ct-DNA) have been studied using circular dichroism and fluorescence spectroscopy. Docking simulations have been carried out to gain more information about the interaction of the palladacycle and HSA. The ability of compounds 1-4 to inhibit the activity of cathepsin B and L has also been investigated in this work.

: Foram efetuadas reações entre o heterometálico [WCl(CO)3(bipy)(HgCl)], (bipy = 2,2'-bipiridina) e tiouréias que levaram à formação de compostos do tipo [WCl(CO)3(bipy)(HgCl)L] [L = tiouréia (tu); N-metiltiouréia (mtu); N,N-dimetiltiouréia (dmtu)]. Os espectros de absorção no infravermelho mostram que a esfera de coordenação do tungstênio mantêm-se inalterada e que as tiouréias encontram-se ligadas ao átomo de mercúrio através do átomo de enxofre.

The bridge-splitting reaction between [Pd(C-2,N-aphox)(mu-Cl)](2) and phosphines (L), in a 1:2 ratio, yielded neutral mononuclear cyclopalladated compounds of the type [PdCl(C-2,N-aphox)(L)] faphox = aceto-phenoneoxime; L= triphenylphosphine (1), tris(4-fluorophenyl)phosphine (2), tri-cyclohexylphosphine (3), diphenyl(p-toluyl)phosphine (4), tris-(4-methoxyphenyl)phosphine (5) and tri(p-toluyl)phosphine (6)). The compounds were characterized by elemental analyses, IR and H-1-, C-13{H-1)- and (31)p{H-1}-NMR spectroscopies. The crystal and molecular structures of 1-5 were determined by single-crystal X-ray diffraction. After that, the Hirshfeld surface calculations were carried out to explore the nature and major contributions of different intermolecular contacts towards crystal packing stability. (C) 2018 Elsevier B.V. All rights reserved.

The reactions between [PdCl2(tmbiimH2)]·H2O (1) tmbiimH2 = 2,2'-bis(4,5-dimethylimidazole) and thiourea (tu), N-methylthiourea (mtu), N-phenylthiourea (ptu), N,N'-dimethylthiourea (dmtu) or N,N'-diphenylthiourea (dptu) in the 1:2 molar ratio resulted in the compounds [PdL2(tmbiimH2)]Cl2·nH2O L = tu (2), mtu (3), ptu (4), dmtu (5) and dptu (6), which were characterized by elemental analyses, infrared (IR), and 1H NMR spectroscopies and conductivity measurements. The IR spectra of 1-6 were consistent with the presence of chelating tmbimH2 ligand. All compounds and cisplatin were tested in vitro by MTT assay for their cytotoxicity against three murine cancer cell lines: mammary adenocarcinoma (LM3), lung adenocarcinoma (LP07) and mouse fibroblast (L929) cells. Relating the series of compounds to their biological activities we found compound 6 as the most promising of them.

Este trabalho trata do emprego do ciclometalado [Pd(dmba) (NCO)(PPh 3 )] (dmba = N,N- dimetilbenzilamina; PPh 3 = trifenilfosfina) em processos catalíticos em fase homogênea, envolvendo a reação entre p-toluidina e p-nitrotolueno, produzindo N,N’-bis(4-metilfenil)uréia. A reação foi realizada a 140 0 C, sob pressão inicial de CO de 60 bar. Empregou-se também o mesmo composto em reações de carbonilação na presença dos álcoois metílico e etílico, obtendo-se os alcoxicarbonil complexos [Pd(NCO)(CO 2 R)(PPh 3 ) 2 ] (R=Me ou Et). Constatou-se que o emprego do [Pd(dmba)(NCO)(PPh 3 )] nos referidos processos, propiciou a formação dos produtos com bons rendimentos.

Ciclopaladados diméricos do tipo [Pd(dmba)(m-X)] 2 (dmba = N,N-dimetilbenzilamina; X = Cl, N 3 , NCO) reagem com tiouréia (tu), à temperatura ambiente, resultando espécies mononucleares do tipo [Pd(dmba)(X)(tu)]. Todos os compostos foram caracterizados por análise elementar, espectroscopias no IV e de RMN de 1 H e com base nessas técnicas as estruturas, desses compostos, foram propostas. Os espectros de absorção no infravermelho mostraram que a coordenação da tiouréia, ao paládio, ocorre através do átomo de enxofre. O anel ciclometalado foi confirmado através da espectroscopia de RMN de 1 H.

No presente trabalho é descrita a investigação do comportamento térmico de uma nova série de complexos ciclopaladados, obtidos a partir de reações do azido-complexo [Pd(dmba)(m-N3)]2 (1) (dmba = N,N-dimetilbenzilamina) com os azo-ligantes aniônicos pirazolato (pz), imidazolato (imz) e 3,5-dimetil-pirazolato (3,5-dmpz). Os compostos binucleares [Pd(dmba)(m-pz)]2 (2), [Pd(dmba)(m-imz)]2 (3) e [Pd(dmba)(m-3,5-dmpz)]2 (4) foram caracterizados por análise elementar, espectroscopia de absorção na região do infravermelho, espectroscopia de RMN de 13C{1H} e 1H e análise termogravimétrica. O produto final de decomposição térmica, paládio metálico, foi caracterizado pela difratometria de raios-X, método do pó.

Este trabalho contempla a síntese e caracterização espectroscópica de dois compostos carbonílicos heterometálicos do tipo [Fe(CO) 3 (m-CS 2 )(PPh 3 )(CuX)], X = Cl, ClO 4 . Os dados provenientes da espectroscopia no infravermelho e de RMN de 31 P{ 1 H} foram conclusivos quanto à proposição da geometria octaédrica distorcida ao redor do átomo de ferro (0), como também sobre a natureza bimetálica de ambos compostos. Estes dados esclareceram o modo de coordenação dos grupos carbonilos, da trifenilfosfina (PPh 3 ), bem como a disposição do ligante dissulfeto de carbono em ponte entre os átomos de Fe (0) e Cu (I).