Renato Najjar

Interactions of antitumoral platinum-group metallodrugs with albumin

A full understanding of the modes of action of the metal-based antitumoral drugs requires the study of their interactions with all possible biological targets, including aminoacids, hormones, peptides and proteins. Albumin is the most abundant plasma protein and it is reasonable to expect that any injected metal drug will present some kind of interaction with this macromolecule, which could crucially determine its bioavailability and toxicology. However, relatively few detailed mechanistic studies have been performed on such interactions, in comparison to studies with DNA and nucleobases. In this work is presented a review of the research on reactions of platinum(II) and (IV), gold(I) and (III), ruthenium(III) and rhodium(II) antitumoral compounds with serum albumin. Generally, platinum and gold compounds are found to react with S-donors such as methionine and the Cys34 residues of albumin, the latter being the most abundant free thiol in blood plasma. Complexes of ruthenium and rhodium are thought to react mainly through coordination with imidazole groups from histidine residues.

Synthesis and characterization of a diruthenium–ibuprofenato complex: Comparing its anti-inflammatory activity with that of a copper(II)–ibuprofenato complex

The ibuprofen complex of diruthenium(II,III) was prepared and characterized by electronic (UV-Vis) and vibrational (FTIR) spectroscopies and thermogravimetry. The copper(II)-ibuprofenato complex was prepared by a different route from that described in the literature. Both complexes were tested in vivo for anti-inflammatory activity. Oral administration of the two complexes inhibited development of carrageenin-induced edema in rats, this inhibition being similar to that observed for oral administration of the parent drug (free ibuprofen). However, gastric irritation was lower as compared to that of ibuprofen. Diruthenium-ibuprofenato exhibited a protective effect at light intensity ulceration while the copper-ibuprofenato complex was more effective in the protection of severe intensity ulceration.

A CIRCULAR DICHROISM AND FLUORESCENCE QUENCHING STUDY OF THE INTERACTIONS BETWEEN RHODIUM(II) COMPLEXES AND HUMAN SERUM ALBUMIN

Various divalent rhodium complexes Rh2(L)4 (L = acetate, propionate, butyrate, trifluoroacetate and trifluoroacetamidate) have been found to bind to non-defatted human serum albumin (HSA) at molar ratios about 8:1. The circular dichroism measurements showed that the more liposoluble carboxylates, butyrate and trifluoroacetate, caused the major alterations of the secondary structure of HSA. Stern-Volmer constants for the fluorescence quenching of the buried Trp214 residue by these complexes were also higher for the lipophilic metal compounds. In the case of the rhodium carboxylates it was observed that their denaturating and quenching properties could be explained in terms of their liposolubilities: the higher their lipophilic characters, the higher their abilities to penetrate inside the protein framework leading to structural alterations, and the closer they could get to the Trp residue causing fluorescence quenching. The liposoluble amidate complex, Rh2 (tfc)4, presented an intermediate quenching and did not cause structural alterations in the protein, presumably not penetrating inside the peptidic backbone. This study shows that it is possible to design new antitumor metal complexes which bind, to a large extent, to a transport protein causing little structural damage.

Water-soluble rhodium(II) carboxylate adducts: Cytotoxicity of the new compounds

Rhodium(II) carboxylate (acetate, propionate, and butyrate) adducts with isonicotinic acid (Hisonic) were prepared for study. Elemental analyses and electronic spectroscopy show that the adducts contain two isonicotinic acid ligands coordinated in the axial position at the pyridinic nitrogen. The in vitro (K562 human leukemic cell line) assay and LD10 in mice results, in addition to tests of solubility, suggest that, in the presence of blood lipids or cellular membrane, the adducts dissociate into the parent compounds and the rhodium(II) carboxylate enters the cell to carry out its biological effects.

Rh2(CF3CONH)4: The First Biological Assays of a Rhodium (II) Amidate

The rhodium (II) complexes Rh2(tfa)4.2(tfac) and Rh2(tfacam)4 (tfacam = CF3CONH-,tfa = CF3COO-,tfac = CF3CONH2) were synthesized and characterized by microanalysis and electronic and vibrational spectroscopies. Rh2(tfacam)4 was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra-amidate to have its biological activity evaluated. The LD50 value for Rh2(tfacam)4 is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects.

Water Soluble Cyclophosphamide Adducts of Rhodium(II) Keto-Gluconate and Glucuronate. Synthesis, Characterization and In Vitro Cytostatic Assays

The synthesis, characterization and biological assays of two new rhodium carboxylate sugar derivatives and respective cyclosphosphamide adducts are described. The compounds, characterized by 13C and 1H NMR, infrared and UV-visible spectra, presented high water solubility and hydration grades were confirmed given the concordance between thermal and CHN analyses. The adducts were active in vitro against K-562 cells.

Synthesis of rhodium (II) hydrocinnamate and some complexes with nitrogen ligands

Abstract Rhodium(II) hydrocinnamate has been prepared by the reaction of hydro-cinnamic acid with rhodium(II) acetate and has been used to prepare complexes of probable formula [Rh 2 (C 6 H 5 CH 2 CH 2 CO 2 ) 4 L 2 ] (L = imidazole, 2-methylimidazole, pyridine, di-methylamine). IR, Raman, electronic, XPE and NMR ( 1 H) spectra and magnetochemical and thermal analysis data are reported.

Effects of human serun albumin in some biological properties of rhodium(II) complexes

The affinities for human albumin (HSA) of five rhodium(II) complexes of general formula [Rh2(bridge)4] (bridge = acetate, propionate, butyrate, trifluoroacetate and trifluoroacetamidate) were determined by spectrophotometry. In the case of the alkylcarboxylates, an inverse correlation of affinity with their liposolubilities was observed. Diffusion of the free or protein-bound complexes into Ehrlich cells in vitro seems to be primarily governed by the hydrophobic character of the complex. The complex [Rh2(tfc)4] exhibited affinity towards the protein (K = 214.1) as well as cell partition both in the absence (32.1%) and presence (48.6%) of HSA. The compound HSA: [Rh2(tfc)4] has had its antitumoral action in tumor-bearing Balb-c mice investigated, showing that HSA can be a drug reservoir for the rhodium complex.

Potencialidades da utilização de compostos de ródio na confecção de sensores eletroquímicos: uma breve revisão

The electrochemistry field has increased in recent years, specially in the search for new sensors to monitor specific analyte in complex samples. In order to improve electrodes, many rhodium compounds have been used as electron mediators for novel sensors development. The most used compounds for this purpose are metal, metal complexes and some organic dyes. Rhodium complexes are known by their good catalytic properties and it could be useful in the sensor field. However, there are only a few reports, on the use of rhodium complexes in sensors and biosensors. A brief review of the electrochemistry of rhodium complexes and some discription of their properties which make those compounds suitable for development of sensor and biosensor.

The cinnamate complex of rhodium(II) and some of its adducts

Abstract Rhodium cinnamate and some of its adducts were synthesized and characterized through IR and visible spectroscopy, thermogravimetry and magnetic susceptibility. The compounds have the general formula Rh 2 (Cin) 4 ·2L (Cin - cinnamate ion and L = pyridine, imidazole or dimethylamine). The IR spectra show that the carboxylate ions function as bridges between two rhodium atoms. Only one band appears in the visible spectra (600 nm region); this band follows the spectrochemical series reported previously for rhodium acetate adducts [1,2]. When these compounds are heated under nitrogen atmosphere the final product at 310 °C is rhodium metal. Rhodium cinnamate is diamagnetic at 25 °C.