A Trinuclear Heterobimetallic Ru(II)/Pt(II) Complex as a Chemodosimeter Selective for Sulfhydryl-Containing Amino Acids and Peptides Cheuk-Fai Chow, ² Brenda K. W. Chiu, ² Michael H. W. Lam,* ,² and Wai-Yeung Wong ‡ Department of Biology and Chemistry, City UniVersity of Hong Kong, 83 Tat Chee AVenue, Hong Kong SAR, China, and Department of Chemistry, Hong Kong Baptist UniVersity, Waterloo Road, Kowloon Tong, Hong Kong SAR, China Received February 26, 2003; E-mail: bhmhwlam@cityu.edu.hk Chemosensing of amino acids, peptides, and proteins in aqueous media of physiologically relevant conditions is a rapidly developing field. 1 We are particularly interested in sulfhydryl-containing amino acids and peptides as they play many crucial roles in biological systems. 2 Some of them are also important parameters in clinical diagnostics. For example, plasma levels of glutathione (GSH), cysteine (Cys), and homocysteine (Hcys) have been linked to various human diseases such as AIDS, 3 Alzheimer’s and Parkin- son’s diseases, 4 as well as cardiovascular diseases and stroke. 5 The tendency of proteins to bind with labile platinum(II) complexes via sulfhydryl and methionine functionalities 6 suggests that the platinum(II) metal center is a suitable candidate for molecular recognition and binding of sulfhydryl-containing amino acids and peptides. Low-energy metal-to-ligand charge transfer (MLCT) luminescence of coordination and organometallic complexes has been very useful in the transduction of chemosensing signals through biological fluids as it is not masked by the ubiquitous high- energy background fluorescence from sample matrixes. 7 Here, we report the synthesis and characterization of a neutral trinuclear heterobimetallic cyano-bridged Ru(II)/Pt(II) complex, cis-Ru(phen) 2 - [CN-Pt(DMSO)Cl 2 ] 2 (phen ) 1,10-phenanthroline) (1), as a chemodosimetric ensemble 8 for sulfhydryl-containing amino acids and peptides. 3 MLCT emission of cis-[Ru(phen) 2 (CN) 2 ] is quenched upon coordination of the cyano moieties by the electron-accepting Pt(DMSO)Cl 2 moieties. Selective coordination of the Pt(II) centers with Cys, Hcys, methionine (Met), and GSH in aqueous DMF at pH 7 causes the cleavage of the cyano bridge and the restoration of the characteristic orange-red 3 MLCT luminescence of the Ru(II)- diimine chromophore. Complex 1 is formed by stirring 2 equiv of [Pt(DMSO) 2 Cl 2 ] 9 with 1 equiv of cis-[Ru(phen) 2 (CN) 2 ] 10 in chloroform at room temperature. 11 A perspective view of the crystal structure of 1, with atom labeling, is shown in Figure 1. The three metal centers adopt a V-shaped configuration with two Pt(DMSO)Cl 2 moieties bridged to a Ru(II) center via cyano bridges. Such molecular configuration has already been proposed by Bignozzi and Scandola in an analogous complex {Ru(bpy) 2 [CN-Pt(dien)] 2 }(ClO 4 ) 4 (dien ) diethylenetriamine). 12 The coordination geometry of the two Pt(II) centers is square planar with two chloro ligands trans to each other and a coordinated DMSO trans to the cyano bridge. The averaged bond distance between Ru and the cyano-C is 1.961 Å, and that between Pt and cyano-N is 2.001 Å. The two Ru-CtN-Pt bridges are slightly bent from linearity with the mean bond angles of 176.2° at Ru-CtN and 171.4° at CtN-Pt. The mean Pt-S bond distance is 2.208 Å. Integrity of the cyano-bridges of 1 in aqueous DMF (pH 7) is demonstrated by its electrospray-MS showing peaks at m/z 1166 corresponding to [M - Cl] + . Upon coordination of the Pt(DMSO)Cl 2 acceptors, the Ru(dπ) f phen(π*) MLCT transition 13 of the Ru(II)-diimine chromophore shifts from 452 to 384 nm, and the 3 MLCT emission 12 shifts from 621 to 595 nm with a drastic reduction in luminescent intensity. The concomitant blue-shift of the MLCT transitions and the decrease of the 3 MLCT emission intensity are consistent with the coordination of good electron acceptors to the cyano donors of [Ru- (phen) 2 (CN) 2 ]. 12,14 Solventochromic studies of cis-[Ru(phen) 2 (CN) 2 ] have demonstrated the reduction of emission quantum yield, φ em , in solvents with a large Gutmann’s solvent acceptor number, that is, good electron-accepting ability. 14 Figure 2a shows typical luminescent responses of 1 to Cys in aqueous DMF at pH 7. Addition of the thiol amino acid shifts the 3 MLCT emission of the complex from 595 to 621 nm with a significant enhancement in intensity. Figure 2b and 2c summarizes spectrofluorimetric titrations of 1 with common amino acids and GSH. For amino acids, only those with sulfhydryl functionality (Cys, Hcys, and Met) are able to induce the spectrofluorometric responses. GSH, a cysteine-containing small peptide, is also found to be able to produce similar results. It is envisioned that 1 can also respond to other sulfhydryl-containing peptides. ² City University of Hong Kong. ‡ Hong Kong Baptist University. Figure 1. Perspective view of cis-{Ru(phen)2[CN-Pt(DMSO)Cl2]2} (1). Selected bond lengths (Å) and angles (deg): Ru(1)-N(1) 2.082 (8), Ru(1)- N(2) 2.107 (8), Ru(1)-N(3) 2.073 (7), Ru(1)-N(4) 2.124 (8), Ru(1)-C(25) 1.954 (12), Ru(1)-C(26) 1.966 (11), Pt(1)-N(5) 2.013 (10), Pt(2)-N(6) 1.987 (9), Pt(1)-Cl(1) 2.275 (4), Pt(1)-Cl(2) 2.284 (4), Pt(2)-Cl(3) 2.295 (3), Pt(2)-Cl(4) 2.287 (3), Pt(1)-S(1) 2.206 (3), Pt(2)-S(2) 2.210 (3). C(25)-Ru(1)-C(26) 86.7 (4), N(5)-C(25)-Ru(1) 173.9 (10), N(6)- C(26)-Ru(1) 178.4 (9), C(25)-N(5)-Pt(1) 169.5 (10), C(26)-N(6)-Pt(2) 173.3 (9), N(5)-Pt(1)-Cl(1) 89.2 (3), N(5)-Pt(1)-Cl(2) 89.2 (3), N(6)- Pt(2)-Cl(3) 89.5 (3), N(6)-Pt(2)-Cl(4) 86.6 (3), Cl(1)-Pt(1)-Cl(2) 175.14 (18), Cl(3)-Pt(2)-Cl(4) 175.76 (12), N(5)-Pt(1)-S(1) 175.0 (3), N(6)- Pt(2)-S(2) 178.7 (3) Published on Web 06/04/2003 7802 9 J. AM. CHEM. SOC. 2003, 125, 7802-7803 10.1021/ja034891x CCC: $25.00 © 2003 American Chemical Society