A different 'spin' on Rhenium chemistry. Synthetic approaches and perspectives of 17-electron Rhenium complexes

Transition metal complexes of rhenium and technetium find wide application in nuclear medicine and the chemistry of these elements is still the focus of intense research efforts. For therapeutic and diagnostic applications, currently much attention is dedicated to the development of new targeting strategies aimed at appending the metal complexes to biological vectors (e.g. a peptide) for a site-specific delivery of the radio-nuclides. Advancements in radiopharmacy, however, will not only arise from the development of new targeted strategies but also from the exploration of the chemistry of these elements in their unusual oxidation states. In this respect the even number oxidation states of Re and Tc (i.e. +II, +IV and +VI) are relatively poorly understood. In particular, stable and substitutionally labile mononuclear 17-electron species of the elements (+II, d(5)) are a rarely encountered class of complexes. In this review we present our recent developments in the field of rhenium (II) chemistry with emphasis on the novel synthetic strategies we have recently introduced. We will also describe how the unique chemical and electronic properties of Re(II)-based complexes may provide a potentially new approach for applications in inorganic medicinal chemistry

Ligand electronic parameters as a measure of the polarization of the C≡O bond in [M(CO)(x)L(y)]n complexes and of the relative stabilization of [M(CO)(x)L(y)](n/n+1) species

The electronic description of octahedral (fac-M(CO)(3)L-3](n), with M = Re, Ru, and Mn, and Cr(CO)(5)L](n)), square-planar (cis-Pt(CO)(2)L-2](n)), and tetrahedral (Ni(CO)(3)L](n)) carbonyl complexes (where L=monodentate ligand) was obtained via density functional theory and natural population analyses in order to understand what effects are probed n these species by vibrational spectroscopy and electrochemistry as a function of the ligand electronic parameter of the associated L. The analysis indicates that while ligand electronic parameters may be considered as a measure of the net donor power of the ligand, the net transfer of the electron density (or charge) does not occur from the ligand to the metal ion. In M(CO)(x)L-y](n) carbonyl species, the charge transfer occurs from the ligand L to the oxygen atom of the bound carbon monoxides. This charge transfer translates into changes of the polarization (or permanent dipole) and the covalency of the C O bonds, and it is this effect that is probed in IR spectroscopy. As the analysis shifts from IR radiations to electrochemical potentials, the parameters best describe the relative thermodynamic stability of the oxidized and reduced M(CO)(x)L-y](n/n+1) species. No relationship is found between the metal natural charge of the M(CO)(x)L-y](n) fragments analyzed and the parameters. Brief considerations are given on the possible design of CO-releasing molecules

Reactivity of 17 e(-) Complex Re(II)Br(4)(CO)(2)](2-) with Bridging Aromatic Ligands. Characterization and CO-Releasing Properties

Carbon monoxide releasing molecules (CO-RMs) are a newly emerging class of compounds of pharmacological interest. Among the transition metal-based CO-RMs, 17-electron complexes of general formula cis-trans-Re(II)(CO)(2)Br(2)L(2)] are promising candidates but their poor hydrophilicity hampers future applications. In an effort to increase water solubility of d(5) dicarbonyl rhenium CO-RMs, the reaction of the cis-Re(II)(CO)(2)Br(4)](2-)anion with bridging aromatic ligands of the pyridine and diazine type was investigated. Mononuclear and binuclear complexes are presented and it is shown that the nature of the bridging ligand critically dictates the formation of either species. Most complexes retained their fundamental CO-releasing properties. The synthesis of the molecules together with structural, spectroscopic and theoretical details are discussed

CO releasing properties and cytoprotective effect of cis-trans-[Re(II)(CO)2Br2L2]n complexes

The carbon monoxide (CO) releasing properties of a series of rhenium(II)-based complexes of general formula cis-trans-[Re(II)(CO)(2)Br(2)L(2)](n) and cis-trans-[Re(II)(CO)(2)Br(2)N[intersection]N] (where L = monodentate and N[intersection]N = bidentate ligand) are reported. Complexes evaluated in this study were obtained from direct ligand substitution reactions of the cis-[Re(II)(CO)(2)Br(4)](2-) synthon (2) recently described. (1) All molecules have been fully characterized. The solid-state structures of the cis-trans-[Re(II)(CO)(2)Br(2)L(2)] (with L = N-methylimidazole (3), benzimidazole (4) and 4-picoline (5)) and the cis-trans-[Re(II)(CO)(2)Br(2)N[intersection]N] (with N[intersection]N = 4,4'-dimethyl-2,2'-bipyridine (8) and 2,2'-dipyridylamine (11)) adducts are presented. The release of CO from the cis-trans-[Re(II)(CO)(2)Br(2)L(2)](n) complexes was assessed spectrophotometrically by measuring the conversion of deoxymyoglobin (Mb) to carbonmonoxy myoglobin (MbCO). Only compounds bearing monodentate ligands were found to liberate CO. The rate of CO release was found to be pH dependent with half-lives (t(1/2)) under physiological conditions (25 degrees C, 0.1 M phosphate buffer, and pH 7.4) varying from ca. 6-43 min. At lower pH values, the time required to fully saturate Mb with CO liberated from the metal complexes gradually decreased. Complex 2 and the cis-trans-[Re(II)(CO)(2)Br(2)(Im)(2)] adduct (with Im = imidazole (6)) show a protective action against "ischemia-reperfusion" stress of neonatal rat ventricular cardiomyocytes in culture

Syntheses, structures and reactivities of [CpTc(CO)3X]+ and [CpRe(CO)3X]+

We have synthesized the [Cp*MIII(CO)3Br]+ complexes (M = Re, 99Tc) and studied their basic chemistry in water and in organic solvents in order to understand if these complexes could be synthons for the preparation of new Re- and 99Tc-based cyclopentadienyl cores for (radio)pharmaceutical applications. The [Cp*MIII(CO)3Br]Br [M = Re (1), 99Tc (1a)] complexes were obtained in nearly quantitative yield from the reaction of the corresponding [Cp*MI(CO)3] with Br2 in cold toluene. Compounds 1 and 1a are photo- and thermally unstable and undergo rapid, bromide concentration-dependent redox reactions at room temperature generating the stable [Cp*MIII(CO)3Br][(CO)3MI(-Br)3MI(CO)3] [M = Re (2), 99Tc (2a)] species as main products. Reaction of 1 with AgSbF6 gives rise to the redox-stable complex [Cp*ReIII(CO)3Br]SbF6 (3). In water, 1 and 1a produces a mixture of cis/trans-[Cp*MIIIBr2(CO)2] isomers [M = Re (cis/trans-4), 99Tc (cis/trans-4a)] via CO release. In methanol, 3 reacts with the solvent to generate the methoxycarbonyl complex trans-[Cp*ReIII(CO)2Br(COOCH3)] (5). Compound 5 is stable under basic conditions. In acidic media it is converted into [Cp*ReI(CO)3] as the major product. Kinetic studies with 13C labelled formic acid indicate that formic acid, generated from rapid hydrolysis of methyl formate released from 5, is the reducing agent and the source of CO. Reaction of 1 with 3-fluorobenzyl alcohol (3-FBA), chosen as a simple model of fluorouracil, gives the corresponding alkoxycarbonyl complex [Cp*ReIII(CO)2Br(COOCH2-C6H4F)] (7). Under acidic conditions 7 rapidly releases 3-FBA to give [Cp*ReI(CO)3]. Compounds 2, 2a, cis-4, trans-4a and 5 were structurally characterized.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008

Post-protein-binding metal-mediated coupling of an acridine orange-based fluorophore

The HEW lysozyme (Lys) and the fac-[Re(CO)3(H2O)3]+ complex (1) are used as a simple model system for the description of a new approach to the labelling polypeptides with fluorescent tags. The strategy takes advantage of the reaction of an acridine orange-based fluorophore (AO) with the non-native metal fragment 1 hybridized on the enzyme. A synthetic methodology for the quantitative metallation of the protein is first described and it is then shown that the exogenous metal complex can be exploited for the coupling of the fluorescent probe. All Lys-derived species were characterized by various spectroscopic techniques. It is shown that the approach does not significantly alter the activity of the final fluorescent metallo-protein conjugate (Lys2). The accumulation of Lys2 on Micrococcus lysodeikticus bacteria was observed via confocal laser scanning microscopy

Binding of 9-methylguanine to [cis-Ru(2,2'-bpy)2]2+: First X-ray structure of a cis-bis purine complex of ruthenium.

Reaction of [cis-Ru(2,2'-bpy)2(O3SCF3)2] (1) with 9-methylguanine (9-MeG) affords the cis-[Ru(2,2'-bpy)2(9-MeG)2]2+ complex (2) in good yield. Two bases bind to the metal center via the N7 atoms. X-ray structure analysis of 2(SO3CF3)2 (monoclinic, P2(1)/n, a = 12.5159(6) A, b = 20.0904(13) A, c = 17.1202(9) A, beta = 98.981(6) degrees, V = 4252.1(4) A(3), Z = 4) reveals that the two bases are in a head-to-tail (HT) orientation with base-base dihedral angle of 60.4 degrees. NMR studies confirm that the complex is stable in water for hours, and no evidence for guanine substitution by solvent molecules was found

Formation and Reactivity of [(tacn)-N-CO-ReIIIBr(CO)2]+ in Water: a Theoretical and Experimental Study

The chemistry of [(tacn)-N-CO-ReIII(CO)2Br]X (X = Cl or Br), obtained in good yield from the reaction of fac-[(tacn)ReI(CO)3]Br (1, tacn = 1,4,7-triazacyclononane) with X2 in water, is described. The [(tacn)-N-CO-ReIII(CO)2Br]X complex (2 with X = Br−; 2a with X = BrCl2−), which we have previously communicated, is characterized by an unusual three-membered ring acyl amide bond. Complex 2 is stable as a solid but is reactive in aqueous solution. Under basic conditions (1 M NaOH), reductive decarbonylation was observed, and the bis-carbonyl complex [(tacn)ReI(CO)2Br] (3) was obtained in quantitative yield. The Br− ligand in 3 could be replaced by CN−, giving the neutral complex [(tacn)ReI(CO)2(CN)] (4). In acidic media (1 M HBr), complex 2 partially converted to the monocarbonyl μ-oxo bridged dinuclear complex {[(tacn)ReIII(CO)Br]2O}2+ (5 as [PF6]− salt). Under mild oxidative conditions the trioxo [(tacn)ReVIIO3](ReO4−) (6) was formed almost quantitatively, and small amounts of the uncommon ReVI complex [(tacn)ReVIO2Br](ReO4−) (7) were identified. Mechanistic investigations at the density functional level of theory (DFT) showed that the elementary steps in the formation of 2 from 1 and 3 from 2 involved reactions of the complexes with hydroxide. The calculated pathway is strongly exothermic (ca. −137 kcal/mol), confirming the energetically and kinetically highly favored formation of 3. The X-ray structures of 2a and 3−5 are reported and discussed

Toward novel DNA binding metal complexes: structure and basic kinetic data of [M(9MeG)2(CH3OH)(CO)3]+(M = 99Tc, Re).

To study the interaction of the fac-[M(CO)(3)](+) moiety (M = (99m)Tc, (188)Re) with DNA bases, we reacted [M(OH(2))(3)(CO)(3)](+) with 9-methylguanine (9-MeG), guanosine (G), and 2-deoxyguanosine (2dG). Two bases bind to the metal center via the N7 atoms. X-ray structure analysis of [(99)Tc(CH(3)OH)(9-MeG)(2)(CO)(3)](+) (4) (monoclinic, I2/a, a = 28.7533(14) A, b = 8.0631(4) A, c = 32.3600(15) A, beta = 91.543(6) degrees, V = 7499.6(6) A(3), Z = 8) and [Re(OH(2))(9-MeG)(2)(CO)(3)](+) (7) (monoclinic, P2(1)/n, a = 12.2873(11) A, b = 16.0707(13) A, c = 14.1809(16) A, beta = 103.361(12) degrees, V = 2724.4(5) A(3), Z = 4) reveals that the two bases are in a head-to-tail (HT) orientation. Kinetic studies show that the rates of substitution of the purine bases are comparable to that of one of the active forms of cisplatin. The bis-substituted complexes are generally less stable than the platinum adducts, and metalation of the bases is reversible

Vitamin B12 as a ligand for technetium and rhenium complexes.

No Abstract availabl