Abstract
The reactions of [Ru(NO)Cl5]2– with glycine (Gly), l-alanine (l-Ala), l-valine (l-Val), l-proline (l-Pro), d-proline (d-Pro), l-serine (l-Ser), l-threonine (l-Thr), and l-tyrosine (l-Tyr) in n-butanol or n-propanol afforded eight new complexes (1–8) of the general formula [RuCl3(AA–H)(NO)]−, where AA = Gly, l-Ala, l-Val, l-Pro, d-Pro, l-Ser, l-Thr, and l-Tyr, respectively. The compounds were characterized by elemental analysis, electrospray ionization mass spectrometry (ESI-MS), 1H NMR, UV–visible and ATR IR spectroscopy, cyclic voltammetry, and X-ray crystallography. X-ray crystallography studies have revealed that in all cases the same isomer type (from three theoretically possible) was isolated, namely mer(Cl),trans(NO,O)-[RuCl3(AA–H)(NO)], as was also recently reported for osmium analogues with Gly, l-Pro, and d-Pro (see Z. Anorg. Allg. Chem.2013, 639, 1590–1597). Compounds 1, 4, 5, and 8 were investigated by ESI-MS with regard to their stability in aqueous solution and reactivity toward sodium ascorbate. In addition, cell culture experiments in three human cancer cell lines, namely, A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma), were performed, and the results are discussed in conjunction with the lipophilicity of compounds.
Highlights
Nitric oxide plays important roles in biochemical processes1 and, in particular, in progression of human tumors.2 The antimetastatic activity of NAMI-A, an investigational drug in phase II clinical trials,3 was suggested to be related to its interaction with NO in vivo.4 Given the importance of NO as a noninnocent ligand in coordination chemistry,5 the occurrence of structural trans effects (STEs), the role of the metal-nitrosyl unit as a reaction mediator or regulator of geometry around the metal ion,6 as well as linkage isomerization of the N- and Obound nitrosyl ligand,7 surprisingly little is known about the reactivity of ruthenium(II)- and osmium(II)-nitrosyl compounds with respect to amino acids
We were interested in the study of the reactions of rutheniumnitrosyl complexes with all amino acids except two already reported in the literature with L-His and L-Met,10,11 isolation of the resulted products, and testing antiproliferative activity of all prepared products, including [RuCl2(L-His−H)(NO)] and [RuCl2(L-Met−H)(NO)], reported previously
Reactions of potential anticancer drugs with amino acids have been studied by different groups,32,43,44 but mainly in solution by 1H NMR spectroscopy without isolation of the resulting products
Summary
Nitric oxide plays important roles in biochemical processes and, in particular, in progression of human tumors. The antimetastatic activity of NAMI-A, an investigational drug in phase II clinical trials, was suggested to be related to its interaction with NO in vivo. Given the importance of NO as a noninnocent ligand in coordination chemistry, the occurrence of structural trans effects (STEs), the role of the metal-nitrosyl unit as a reaction mediator or regulator of geometry around the metal ion, as well as linkage isomerization of the N- and Obound nitrosyl ligand, surprisingly little is known about the reactivity of ruthenium(II)- and osmium(II)-nitrosyl compounds with respect to amino acids. We report on the synthesis of eight new ruthenium(II)-nitrosyl complexes with Gly, L-Ala, L-Val, L-Pro, D-Pro, LSer, L-Thr, and L-Tyr (Chart 1), their X-ray diffraction Chart 1 structures, spectroscopic and electrochemical properties, lipophilicity, behavior in aqueous solution, and antiproliferative activity in human cancer cell lines in vitro. The latter was compared to that of osmium-nitrosyl complexes with Gly (1*), L-Pro (4*), and D-Pro (5*).
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