Design and Development of the First Peptide-Chelating Bisphosphane Bioconjugate from a Novel Functionalized Phosphorus(III) Hydride Synthon.

Remarkable oxidative stability is shown by the carboxylate-functionalized primary bisphosphane 1. Compound 1 can be used in conjugation reactions with biomolecules for functionalization through the COOH group without prior protection of PH2 groups. A novel water-soluble bisphosphane was obtained by reaction of the PH2 groups of 1 with formaldehyde under mild conditions.

Chemistry of Bifunctional Photoprobes. 1. Perfluoroaryl Azido Functionalized Phosphorus Hydrazides as Novel Photoreactive Heterobifunctional Chelating Agents: High Efficiency Nitrene Insertion on Model Solvents and Proteins.

Synthesis and evaluation of a new class of photochemically activated heterobifunctional chelating agents for protein modification is described. Selective functionalization of perfluoroaryl azides by versatile phosphorus hydrazide ligating systems 2 and 3 for the complexation of transition metals and analogous radiometals form the basis for these new agents. The utility of the photogenerated precursors from these bifunctional agents to form covalent attachments is demonstrated through examination of C-H bond insertion on cyclohexane. Representative amide-coupled phosphorus hydrazides 5 and 6 provide >78% insertion of the probe into unactivated C-H bonds of cyclohexane with short photolysis times. Photoconjugation of the photoactivable heterobifunctional chelating agent 6 and its Pd metalated analog 7 with HSA is also evaluated. The uncomplexed chelate appears to add to HSA with high efficiency, consistent with the observed 82% bond insertion into model solvents. Covalent attachment of 7, evaluated through the use of (109)Pd, was estimated to be between 49% and 74% with the uncertainty arising because of prephotolysis association of the (109)Pd complex with HSA. The application of in situ (19)F NMR to distinguish between bond insertion and noninsertion processes is demonstrated. These results suggest that functionalized perfluoroaryl azido phosphorus hydrazides may find utility as heterobifunctional photolabeling agents for attaching radionuclides to proteins and antibodies.

Synthesis and Coordination Chemistry of the First Water-Soluble Dithio-Bis(phosphine) Ligands [(HOH(2)C)(2)P(CH(2))(2)S-X-S(CH(2))(2)P(CH(2)OH)(2)] (X = (CH(2))(3) or C(6)H(4)). X-ray Crystal Structure of [Pd(HOH(2)C)(2)P(CH(2))(2)S(CH(2))(3)S(CH(2))(2)P(CH(2)OH)(2)](Cl)(2)(1).

The thioether-functionalized, water-soluble, bis(phosphines) (HOH(2)C)(2)PCH(2)CH(2)S(CH(2))(3)SCH(2)CH(2)P(CH(2)OH)(2) (9) and C(6)H(4){1,2-SCH(2)CH(2)P(CH(2)OH)(2)}(2) (10) were synthesized in near quantitative yields by the formylation of the appropriate phosphine hydrides in the presence of formaldehyde in ethanol. The reactions of 9 and 10 with Pt(COD)Cl(2) and Pd(C(6)H(5)CN)(2)Cl(2) in biphasic media (aqueous/organic) produced the water-soluble Pt(II) and Pd(II) complexes [Pt(HOH(2)C)(2)P(CH(2))(2)S(CH(2))(3)S(CH(2))(2)P(CH(2)OH)(2)](Cl)(2) (11), [Pd(HOH(2)C)(2)P(CH(2))(2)S(CH(2))(3)S(CH(2))(2)P(CH(2)OH)(2)](Cl)(2) (12), [Pt{(C(6)H(4)){1,2-S(CH(2))(2)P(CH(2)OH)(2)}(2)}](Cl)(2) (13), and [Pd{(C(6)H(4)){1,2-S(CH(2))(2)P(CH(2)OH)(2)}(2)}](Cl)(2) (14) in near quantitative yields. The X-ray crystal structure of 12 confirms a square-planar Pd(II) structure for this new generation of water-soluble transition metal complexes. All of the complexes were characterized by MS, (1)H, (13)C, and (31)P NMR spectroscopy. X-ray data for 12: triclinic, P&onemacr;, a = 9.9761(6) Å, b = 10.2049(7) Å, c = 11.6954(7) Å, alpha = 67.730(10) degrees, beta = 69.943(10) degrees, gamma = 79.828(10) degrees, Z = 2, R = 0.0307 (R(w) = 0.0797).