Khajadpai Thipyapong

Insight into Technetium Amidoxime Complex: Oxo Technetium(V) Complex of N-Substituted Benzamidoxime as New Basic Structure for Molecular Imaging

In search of benzamidoxime (BHam) derivatives that provide a single (99m)Tc-labeled compound of high in vivo stability, we synthesized three N-alkyl compounds of benzamidoxime (BHam) ligand. They provided a single (99m)Tc-labeled compound by ligand exchange reaction of (99m)Tc-glucoheptonate in high radiochemical yields (over 95% at MBHam concentration of 1 × 10(-5) M). (99m)Tc-N-methyl benzamidoxime ((99m)Tc-MBHam) showed higher stability than the parental (99m)Tc-BHam. The complex of this compound with (99g)TcO(3+) ion was prepared, isolated, and characterized by FT-IR and NMR spectra as well as X-ray diffraction. (99g)Tc-MBHam crystallized in an orthorhombic space group Pna2(1) with a = 13.4823(5), b = 15.5410(7), c = 7.7907(3) Å, V = 1632.39(11) Å(3), and Z = 4. The (99g)Tc complex possessed square base pyramid coordination geometry. The equatorial plane was formed by two-amine nitrogen and two-oxime oxygen atoms in trans position, while the oxo core of the technetium(V) occupied the apical position. The (99g)Tc-MBHam proved to be identical with the (99m)Tc-MBHam prepared at the no-carrier-added level by comparison of their HPLC profiles.

Assessment of macrocyclic triamine ligands as synthons for organometallic 99mTc radiopharmaceuticals.

In a search of coordination molecules suitable to the fac-{(99m)Tc(CO)3}(+) core as a synthon for (99m)Tc-radiopharmaceuticals, nonradioactive rhenium complexes of two macrocyclic triamine compounds with different chelate ring structures, 1,4,7-triazacyclononane (9N3) and 1,5,9-triazacyclododecane (12N3), were synthesized and characterized. (99m)Tc-labeled 9N3 and 12N3 compounds were also prepared using [(99m)Tc(OH 2)3(CO)3](+) and were characterized by both in vitro and in vivo studies. 9N3 produced a single rhenium complex, whereas 12N3 generated two major complexes. The crystallographic data and infrared absorption wavenumber assigned to the C-O stretch suggested that the coordination geometry of 9N3 would be more suitable to fac-{Re(CO)3}(+) than that of 12N3. In contrast, both 9N3 and 12N3 provided a single (99m)Tc-labeled compound. However (99m)Tc-labeled 9N3 exhibited higher stability than (99m)Tc-labeled 12N3 in rat plasma and in the presence of histidine at an elevated temperature. In biodistribution studies, both (99m)Tc-labeled compounds did not show any specific accumulation of radioactivity in any organs except for the excretory organs such as the liver and kidney. These findings showed that 9N3 would constitute a macrocyclic chelating molecule of choice to prepare (99m)Tc radiopharmaceuticals using a fac-{(99m)Tc(CO)3}(+) core.

Exploring molecular structures, orbital interactions, intramolecular proton-transfer reaction kinetics, electronic transitions and complexation of 3-hydroxycoumarin species using DFT methods.

Optimal structures and electronic properties of various species of 3-hydroxycoumarin (3-HCou) have been explored using density functional theory (DFT) methods under polarizable continuum model (PCM) of solvation. Electron transfer from pyrone to benzene moieties is enhanced upon deprotonation. Anionic and radical species have similar orbital-interaction characteristics but the charges in the former are distributed more uniformly. The rate of intramolecular proton transfer for the neutral species increases many folds upon excitation. The HOMO-LUMO transition with π→π* character mainly accounts for the UV absorption of most 3-HCou species in solution. The wavelengths of maximal absorption predicted using TD-DFT method are in agreement with the previous experiment. For the charged species, calculations with the range-corrected functional yield better agreement with the previous experiment. Anionic 3-HCou species shows high degrees of complexation with chromium(III) and copper(II) compared with oxovanadium(IV) and zinc(II). Either oxovanadium(IV) or zinc(II) prefers forming two isomeric complexes with comparable degrees of formation.

Substituent effect on the proton-related phenomena and chelation behavior of hydroxypicolinic compounds: a DFT investigation

Comparative study on kinetics and thermodynamics of proton-related reactions of hydroxypicolinic acids has been carried out using density functional theory associated with polarizable continuum model of solvation. Mechanisms for such reactions have been established. Both 3- and 4-hydroxypicolinic acid prefer zwitterionic forms to normal forms. For 6-hydroxypicolinic acid, keto forms are highly preferred. The pKa values and UV/Vis bands predicted for some picolinic compounds agree with the experiment. 5-Hydroxypicolinate shows the highest preference for complexation with copper(II) but 6-hydroxypolinate gives rise to the most stable complex. Kinetic stability of the trans-isomer relative to the cis-isomer of the complexes has been evaluated. UV/Vis spectral data predicted for some picolinate complexes are also in agreement with the previous experiment.

Complexation reactions, electronic properties, and reactivity descriptors of cysteamine-based ligands in aqueous solution: a PCM/DFT study

Computational approaches based on density functional theory (DFT) combined with polarizable continuum model (PCM) of solvation have been used to probe the likelihood of complexation in water between oxo-vanadium(IV) and various medicinal cysteamine-based ligands. The experimental electronic spectra of a complex formed by oxo-vanadium(IV) and penicillamine in water agree well with the theoretical spectra based on the time-dependent density functional theory (TD-DFT) calculations. Among all density functionals adopted, CAM-B3LYP outperforms the others in predicting both structural and spectroscopic properties of oxo-transition metal complexes of cysteamine-based ligands. A variety of chelation behaviors have been found for the ligands tested, depending on the choice of substituent added to the cysteamine backbone. Solvation has a great impact on the thermodynamic driving force for cysteine and its derivatives to undergo complexation. In all cases, the thiolate sulfur atom forms stronger coordination bond than either the amine nitrogen or carboxylate oxygen atoms. Based on the thermodynamic and nucleophilicity index calculations, penicillamine has the highest potential to form complex with oxo-vanadium(IV).