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Research has been conducted on the X-ray structurally characterized rhenium complexes. The preparation of these complexes from the protected amine-diamine-thiol ligands is discussed.

Research has been conducted on the radiopharmaceuticals. The factors leading to one isomeric species in one ionization state at physiological pH are analyzed.

Research was conducted to examine the synthesis, structure and solution forms of anti- and syn-Reo(L-cysteine-acetyl-cysteamine) and the dimethyl derivatives anti- and syn-ReO(L-penicillamine-acetyl-cysteamine). Results indicate that the introduction of an electron-withdrawing group into the ligand may lower the NH pKa of the complex below the physiologically relevant range and yield a species with a well-defined charge.

A novel method for investigating changes in fluxional Re(V)=O complexes of the analogous meso N2S2 ligands using nuclear magnetic resonance spectroscopy was developed. The new strategy used ligands with selected stereochemical features such as meso isomers of EC-type ligands. It was found that ReO has predominant from between pH 6 and 10 with the usual N2S2 basal donors. This form contains unusual determinant of chirality.

Biochemical research involving a novel class of organocobalt models [LCo(N-CH2-CHEL)]X shows steric bulk binding interaction differences between the ligands of the analogs 1,5,6-trimethylbenzimidazole and N-methylimidazole. Evidence indicates that steric interactions involving the equatorial ligand do not determine the angle of Co-N(5)-C bonds. The highly distorted N4 equatorial ligation seems to be caused by the Me3Bzm Lone pair of electrons.

The structure of [AsPh4][EtSCo(DH)2(CH3)] was analyzed by X-ray crystallography to determine the characteristics of the organocobalt complex. The organocobalt complex is composed of a unidendate coordinated thiolate with a long C-S bond due to the weak trans influence of the thiolate to the Co-C bond. Furthermore, the alkanethiolate ligand is comparable to alkylphosphines in its affinity for axial coordination to B12 models.

Exchange-NOE nuclear magnetic resonance spectroscopy data is shown to be an efficient method for determining the extent of planar N-donor heterocyclic coordinated ligands (L's) rotation about the metal-N bond, the direction of L rotation and even the halves of C2-symmetrical L's that interchange during dynamic processes. It marks the first time that preferred pathways of rotation were demonstrated.

The reaction of thiol-amide-thiourea (TATU) ligand with Re(superV)O complexes yields (1-phenyl-3-(2-((2-thioacetyl)amino)ethyl)thioureato)oxorhenium(V) neutral complex, which is a new N2S2 chelate. The complex has a pseudo square pyramidal geometry with deprotonated thiol S, amide N, thiourea N, and thiocarbonyl S in the basal plane, and oxo group at the apical position. The thiourea unit of TATU ligands forms a four-membered chelate ring, which enables it to synthesize multidentate ligands. X-ray crystallography and NMR spectra are used to characterize the complex.

The ligand exchange interactions between N2S2 dithiourea (DTU) ligands, RNHC(=S)NH(CH2)3NHC(=S)NHR, and Re(V) precursors form neutral Re(super V)=O(N2S2) complexes. Structural studies of (1-phenyl-3-(3-(3-phenylthioureido)propyl)thioureato)oxorhenium(V) indicate a pseudo-square-pyramidal geometry with an apical oxo donor and an N2S2 basal set. One uncoordinated N of the DTU ligands is deprotonated and forms a dianionic four-membered N,S chelate ring. The two coordinated N's are deprotonated.

The Co-C-N three-membered ring in organocobalt complexes related to B12 is formed when an equatorial nitrogen donor is added to a ligated axial carbon through a facile interligand nucleophilic addition. The Co-C-N ring angle is 43.7 degrees with Co-N and Co-C ring linkages having the greatest distortion of the coordination sphere. Phi-bending is a significant factor in the weakening of the Co-C bond, and causes Co-C bond cleavage along with theta-bending. Hypotheses regarding Co-C bond activation in B12 chemistry and calculations of the activation can be assessed using evidence from the highly distorted structure of the resulting complex.

UV-visible, 1H NMR, and Raman resonance spectra indicate that the enantiomers of oxo(D-penicillaminato)(L-penicillaminato)rhenate(V) (1) interconvert in a fast base-catalyzed reaction to trans form (I). Substantial carboxyl group deligation occurs at pH 11, when I is converted to form II. The rate of interconversion is proportional to hydroxyl concentration. Axial hydroxo coordination is favored in 1 compared to ReO(D-penH3)(D-penH2). The NMR spectrum and Re=O band of 1 indicate that II is a trans-dioxo species.

A spectroscopic study at varying pH of ReO(D-penH3)(D-penH2), 1, the neutral form of the known Re(V)=O complex of D-penicillamine, reveals a facile oxo ligand exchange processs. At pH > 11, the monoanion (I) is converted into an NH deprotonated (I') and hydroxoligated (II) forms equilibrium mixture by one equivalent of OH-. The mixture is further converted to the trans-dioxo species II' by an additional equivalent of OH-. Conversion of I' to II is afforded only by a slower deligation method.

X-ray crystallographic studies help determine the structures of rhenium (V) oxo analogues of technetium 99m radiopharmaceuticals for renal function assessment with N2S2 chelate ligands. These complexes have two nonconjugated, deprotonated nitrogens. NMR experiments of the radiopharmaceuticals at biological pH produce a broad NMR spectra due to an interconversion between the two forms at an intermediate rate on the NMR scale. Denticity of the N2S2 ligand differs in both forms, and kidneys transport only one of the two forms of radiopharmaceuticals. Deprotonation at a remote site stimulates the deligation of the other ligating atom.

Three Re(V) oxo complexes derived from isomers of mercaptoacetylglycylglycylaminobenzoic acid were synthesized from ortho-, meta- and para-aminobenzoic acid. The Re coordination spheres of (Ph4P)(ReO MAG2-para-ABAH).H2O and (Ph4P)(ReO MAG2-ortho-ABAH) were found to be square pyramidal with an apical oxo ligand. The only structural difference between the two complexes was the position of the carboxyl group. Calculations were made on the solution phase structures of the three isomeric complexes, including (TcO MAG3)2- which was found to be conformationally flexible.

A study was conducted to identify mononuclear cationic[M(v)=O](super 3+) (M=Tc,Re) complexes for radiopharmaceutical applications. The open-chain ligand, 1,4,8,11-tetraazaundecane-5,7-dione(dioxo-tetH(sub 6)) with two amine and two amide donors were investigated.

The factors dictating the structures and the solution chemistry of Re(V)=O(N(sub 2)S(sub 2)) complexes with ligands derived from cysteine (cys)(super 1-8) was investiaged. The study stated that ligand exchange of the isomeric mixture of TMECH(sub 6) with ReIO(sub 2)(PPh(sub 3))(sub 2) resulted in the formation of a mixture of ReO(TIME(H(sub 3)) isomers.

Syn-ReO(DL-ECH3) has a distorted geometry with very short Re-N bond trans to oxo ligand. X-ray studies show that syn-ReO(DL-ECH3), a M=O(N2S2) complex with M = Re, (super 99)Tc, has NOS2 donor set in the basal plane. M=O(N2S2) complexes, an important class of radiopharmaceuticals, usually are five-coordinate with an N2S2 donor set in the basal plane. But a few of such complexes have a pendant carboxyl group anti to oxo ligand weakly bound to the metal trans to oxo ligand.

The crystalline-octahedral Re2O3Cl4(Me3Bzm)4 (1) and cis,cis, cis-RuCl2(Me2SO)2(Me3-Bzm)2 (2) synthesized from ReOCl3(Me2S)(OPPh3) and cis-RuCl2(Me2SO)4 exhibit a rare head-to-head conformation of untethered lopsided ligands. Properties typical of extremely fluxional species are evident in the H NMR spectra of 1 and 2 in CDCl3.

Two new N2S2 ligands [S-trityl-l-cysteine-acetamide-ethanethiol ethyl ester (Tr-l-CAATH2-Et, 1) and S-trityl-d-penicillamine-acetamide-(2-methyl-2-propanethiol) ethyl ester (Tr-d-TMCAATH2-Et, 2)] were prepared. These ligands, with the electron-withdrawing carboxyl group separated by only two bonds from the NH amine group, belong to monoamide-monoamine-dithiol (MAMA) class of chelates that typically form M(V)O(N2S2) (M=Tc, Re) complexes with the ligand secondary amine pKa of ∼6–7 and both syn and anti isomers. Re(V)O(N2S2) complexes were prepared from 1 and 2 with the dangling ester either syn or anti to the Re&z.dbnd6;O intact or hydrolyzed; the latter, ReO(l-CAATH2) and ReO(d-TMCAATH2) have a carboxyl group needed for renal imaging when M=Tc. The gross structure of syn-ReO(l-CAATH-Et) (3) is typical of Re(V)O(N2S2) complexes. However, within the cys moiety of 3, an intramolecular H-bond between the ester carbonyl oxygen O(4) and the NH (N(2)⋯O(4) distance=2.80 A˚) causes the cys chelate ring to adopt an unusual conformation with the αC (C(5)) atom 0.42 A˚ below the plane defined by the cys S, Re, and N(2) atoms with respect to the Re&z.dbnd6;O group. From molecular mechanics (MM) analysis of ReO(l-CAATH2) models, the lowest-energy syn-ReO(l-CAATH2) structure has a corresponding region similar to that of the X-ray structure for 3, an N(2)H endo with respect to Re&z.dbnd6;O group, a N(2)H⋯O(4) hydrogen bond (2.69 A˚ N(2)⋯O(4) distance) contributing ∼5 kcal mol−1 to its stability and an αC atom deviating 0.24 A˚ from the cys S, Re, and N(2) plane. Computed structures with an exo N(2)H are ∼6 kcal mol−1 less stable than the lowest-energy endo analogue. Below pH ∼7, the 1H NMR spectrum of syn-ReO(d-TMCAATH2) exhibited changes in two pH regions, consistent with sequential protonation of the amine and of the carboxylic group. These experimental and MM results reinforce previous hypotheses about the factors favoring one syn form in one ionization state of M(V)O(N2S2) compounds at physiological pH. [Copyright &y& Elsevier]

Characterizes the small peptide analogues of the mercaptoacetyl-glycylglycylglycyline ligand. Identification of the glycine carboxylate oxygen of the ligand; Use of single-crystal X-ray in characterizing the ligand; Description of the mercaptoacetyltriglycine.

Characterizes relatively unstable anti isomers of cysteine-based radiopharmaceuticals at physiological pH. Examination of the nature of the anti isomers of the close radiopharmaceutical analogue; Spectral characteristics; pH dependence.

States that exploring the chemistry of [ReVO]3+ complexes with benzaldehyde-ammonia titration (BAT) ligands derived from L-cysteine is part of an ongoing research into the design of radio-pharmaceuticals with enhance properties for imaging kidney function. Agents for imaging kidney function; Explanation for the simplicity of the high-PH NMN spectrum of ReO(D-penH3)(D-penH2).

Unlabelled: 99mTc-Mercaptoacetyltriglycine ((99m)Tc-MAG3) and (99m)Tc-L,L-ethylenedicysteine ((99m)Tc-LL-EC) are useful renal radiopharmaceuticals; however, both agents have renal clearances less than that of (131)I-orthoiodohippurate ((131)I-OIH), and (99m)Tc-LL-EC exists in dianionic and monoanionic forms at physiologic pH. In an effort to develop a superior (99m)Tc agent with a rapid clearance comparable with that of (131)I-OIH, we have designed a new ligand system, mercaptoacetamide-ethylene-cysteine (MAEC), which combines important structural features of both MAG3 and EC., Methods: Biodistribution and clearance studies were performed on Sprague-Dawley rats using syn- and anti-(99m)Tc-L- and -D-MAEC coinjected with (131)I-OIH. Studies were also performed by coinjecting each isomer ( approximately 74 MBq [ approximately 2 mCi]) and 7.4-11.1 MBq (200-300 micro Ci) of (131)I-OIH in 3 volunteers with dual-isotope imaging performed using a camera system fitted with a high-energy collimator. Blood samples were obtained from 3 to 90 min after injection and urine samples were obtained at 30, 90, and 180 min., Results: In the rats, <10% of the injected dose remained in the blood at 10 min after injection for all isomers, and the urine dose at 60 min ranged from 84% to 99% that of (131)I-OIH. The clearances of syn- and anti-(99m)Tc-L-MAEC in the rats were higher than the clearances for the D-isomers (P