Douglas E. Berning

198Au-labeled hydroxymethyl phosphines as models for potential therapeutic pharmaceuticals

The development of novel gold-198 complexes with water-soluble phosphines is reported. A series of cationic and hydrophilic 198Au complexes containing the ligands tris(hydroxymethyl)phosphine (THP, 1) 1,2-bis[bis(hydroxymethyl)phosphino]benzene (HMPB, 2), and 1,2-bis[bis(hydroxymethyl)phosphino]ethane (HMPE, 3) were prepared and evaluated as models for potential gold-199 radiopharmaceuticals. The 198Au complexes were formed in high radiochemical purity by simply mixing H198AuCl4 with the respective ligand. The complexes were shown to exhibit high in vitro stability over wide pH ranges and temperatures. However, only the 198Au(HMPB)2+ complex was found to exhibit good in vivo stability. HPLC analyses indicated that the 198Au complexes with these three phosphine ligands produced singular species with similar retention times as compared to their known macroscopic complexes.

In vitro and in vivo characterization of a 99mTc complex with tris(hydroxymethyl)phosphine (THP)

The water-soluble, monophosphine ligand tris(hydroxymethyl)phosphine (THMP) was complexed with 99mTc. The 99mTc-THMP was formed in high radiochemical purity by simply mixing 99mTcO4- with THMP over a wide pH range. In vitro and in vivo studies indicated the complex to be highly stable under the respective conditions. HPLC analysis indicated a singular species with a retention time identical to the known [ReO2(THMP)4]1 complex. Results show that the hydroxymethylphosphine functionality is attractive for use in designing new 99mTc radiopharmaceuticals.

Phosphinimine complexes of technetium(VII): X-ray crystal structure of [Ph3P=NH+2][TcO−4]1

An X-ray diffraction study and the solution chemistry is reported for the very stable ion pair [Ph3P=NH+2][TcO−4]. This compound crystallizes in the orthorhombic system, in space group P212121, with cell dimensions of a = 11.1454(6), b = 11.449(2), and c = 14.570(2)Å, and refining to R = 0.023 and RW = 0.031. Strong hydrogen bonds are formed between the iminium protons and the pertechnetate oxygens (1.89(6) and 2.23(6) Å) in the solid state, and similar hydrogen bonding apparently occurs in aqueous solution to stabilize the phosphiniminium cation to hydrolysis.

CONSTRUCTION OF WATER-SOLUBLE PHOSPHINES, NEW ADVANCES IN AQUEOUS ORGANOMETALLIC CHEMISTRY

Interest in aqueous organometallic chemistry stems from the fact that water-soluble transition metal compounds have found applications as catalysts in commercially-viable industrial processes for bulk and fine chemicals synthesis and also for their continued utility in biomedicine. As a solvent, water is unique because it displays polar and protic properties. The strong propensity of water to involve in hydrogen bonding interactions and its ability to act as a donor ligand to transition metals makes it even more unique, non-toxic and environmentally-benign, medium for chemical and biological use. In order to make the best use of some of the properties of water as a solvent, it is important that the transition metal complexes exhibit high solubility and good kinetic stability (in some instances) in water. Traditionally, phosphines functionalized with charged/polar substituants (e.g. -SO3H, -COOH or -OH) have been used as ligands to produce aqueous-soluble transition metal complexes. Recently, studies in ou...

Systematic Coordination of Water-Soluble Monoand Bidentate Phosphine Ligands to the Organometallic Precursor fac-[Rebr3(Co)3]2-

Abstract As part of our ongoing studies to develop new radiopharmaceuticals (and catalysts) based on water-soluble phosphines for diagnostic and thera- peutic purposes, we are investigating the basic coordination behavior of mono- (PTA) and bidentate (HMPE, HMPB) ligand systems towards the low valent rhenium centerfnc-[ReBr3(CO)3]2−(1) in water and organic solvents at room temperature.