No abstract

The reaction of the ruthenium(II) complex fac-[Ru(CO)(3)Cl(2)(N(1)-thz)] (I hereafter; thz = 1,3-thiazole) with human beta-amyloid peptide 1-28 (Abeta(28)) and the resulting {Ru(CO)(3)}(2+) peptide adduct was investigated by a variety of biophysical methods. (1)H NMR titrations highlighted a selective interaction of {Ru(CO)(3)}(2+) with Abeta(28) histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of Abeta(28); electrospray ionization mass spectrometry (ESI-MS) suggested a prevalent 1:1 metal/peptide stoichiometry and disclosed the nature of peptide-bound metallic fragments. Notably, very similar ESI-MS results were obtained when I was reacted with Abeta(42). The implications of the above findings for a possible use of ruthenium compounds in Alzheimer's disease are discussed.

Radiopharmaceuticals containing the "fac-[M(CO)3]+ " core (M=99mTc, 186Re, or 188Re) have potential as diagnostic or therapeutic agents. Complexes with this core with sp3 amine donors have received little attention. We have studied adducts formed by ENDACH2 (HO2CCH2NHCH2CH2NHCH2CO2H) and ENACH (NH2CH2CH2NHCH2CO2H). Re(CO)3(ENDACH)-A (1A) and Re(CO)3(ENDACH)-B (1B) isomers were obtained by the reaction of ENDACH2 with Re(CO)5Cl. Re(CO)3(ENAC) (2) was obtained by the reaction of ENACH with aqueous [Re(CO)3(H2O)3]+. From single-crystal X-ray data, the three new neutral complexes, 1A, 1B, and 2, have a six-coordinate, pseudo-octahedral Re center with facially coordinated carbonyl ligands. ENDACH- and ENAC- bind facially to Re through both amine nitrogens and one carboxyl oxygen, forming two five-membered chelate rings. The Re(CO)3(ENDACH) isomers have an uncoordinated, dangling -CH2CO2H group, which is an ideal coupling site for attachment to biomolecules. The isomers differ by the configuration of the NH center bearing this dangling group. The H atom of the amine (N2) is endo (near the carbonyl ligands in the basal plane) in 1A and exo (away from carbonyl ligands) in isomer 1B. Isomers reach equilibrium (1A:1B, 70:30) after 3 days at high pH. Density functional structure optimizations were performed for isolated molecules of the type Tc(I)/Re(I)(CO)3(N2O): [Re(CO)3(NH3)2(H2O)]+, [Tc(CO)3(NH3)2(H2O)]+, [Re(CO)3(EN)(H2O)]+ (EN, ethylenediamine), [Tc(CO)3(EN)(H2O)]+, and various models for 1A, 1B, and 2. The computed structures are in good agreement with the X-ray structures. The theoretical and experimental Re-N bond distances usually agree within 0.045 A. The total electronic energy values for the computed 1A and 1B models differ by 0.815 kcal mol(-1), giving an isomer ratio of 80:20, in good agreement with the 1A/1B ratio (70:30) found.