Charalampos Triantis

Synthesis and Characterization of fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] Complexes (M = Re, 99mTc) with Acetylacetone and Curcumin as OO Donor Bidentate Ligands

The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimers disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

New labeled derivatives of the neuroprotective peptide colivelin: synthesis, characterization, and first in vitro and in vivo applications.

Colivelin (CL), first reported in 2005, is the most potent member of the humanin family of neuroprotective peptides with in vitro and in vivo rescuing action against insults associated with Alzheimers disease (AD). The objective of the present work is the design, synthesis and characterization of specific CL derivatives that can be used as molecular probes in the investigation of the unknown mechanism of CL action. Within this framework, three CL derivatives bearing suitable tags, i.e., the fluorescent moiety FITC, the streptavidin-counterpart biotinyl-group, and the (99m)Tc-radiometal chelating unit dimethylGly-Ser-Cys, were developed and subsequently applied in biological evaluation experiments. Specifically, the FITC-labeled derivative of CL was used in confocal microscopy, where specific binding at the periphery of F11 cells was observed; the biotin-labeled derivative of CL was used in an in-house developed ELISA-type assay, where specific and concentration-dependent binding with the β-amyloid peptide of AD was shown; finally, the (99m)Tc-radiolabeled derivative of CL was used in in vivo biodistribution studies in healthy Swiss Albino mice, where 0.58% of the radioactivity administered was measured in the mouse brain 2min after injection. The above first successful applications of the CL probes demonstrate their potential to contribute in the field of neuroprotective peptides.

In vivo biodistribution and imaging studies with a (99m)Tc-radiolabeled derivative of the C-terminus of prothymosin alpha in mice bearing experimentally-induced inflammation.

Graphical abstract No caption available. Abstract Prothymosin alpha (ProT&agr;) is a highly conserved mammalian polypeptide (109 amino acids in man) exerting in vitro and in vivo immunoenhancing activities. Recently, our team has developed a 99mTc‐radiolabeled derivative of the C‐terminal bioactive decapeptide of ProT&agr; ([99mTc]C1) and employed it in in vitro studies, the results of which support the existence of binding sites on human neutrophils that recognize [99mTc]C1, intact ProT&agr; as well as the C‐terminal decapeptide of ProT&agr; and presumably involve Toll‐like receptor 4. In the present work, [99mTc]C1 was administered to Swiss albino mice with experimentally‐induced inflammation for in vivo biodistribution and imaging studies, in parallel with a suitable negative control, which differs from [99mTc]C1 only in bearing a scrambled version of the ProT&agr; decapeptide. The biodistribution data obtained with [99mTc]C1 demonstrated fast clearance of radioactivity from blood, heart, lungs, normal muscle, and predominantly urinary excretion. Most importantly, slow clearance of radioactivity from the inflammation focus was observed, resulting in a high ratio of inflamed/normal muscle tissue (9.15 at 30 min post injection, which remained practically stable up to 2 h). The inflammation‐targeting capacity of [99mTc]C1 was confirmed by imaging studies and might be attributed to neutrophils, which are recruited at the inflamed areas and bear binding sites for [99mTc]C1. In this respect, apart from being a valuable tool for further studies on ProT&agr; in in vitro and in vivo systems, [99mTc]C1 merits further evaluation as a radiopharmaceutical for specific imaging of inflammation foci.

Crystal structure of fac-tricarbon­yl(cyclo­hexyl isocyanide-κC)(quinoline-2-carboxyl­ato-κ2N,O)rhenium(I)

The ReI atom in the molecule of the title compound has a distorted C4NO coordination sphere defined by three carbonyl ligands, one chelating quinaldate anion and one isocyanide ligand. As a result of the trans effect of the isocyanide derivative, one Re—CO bond is elongated.

Crystal structure of fac-tricarbon­yl(quinoline-2-carboxyl­ato-κ2N,O)(tri­phenyl­arsane-κAs)rhenium(I)

In the title rhenium(I) tricarbonyl complex with triphenylarsane and deprotonated quinaldic acid ligands, the ReI atom is in an octahedral coordination. Weak C—H⋯O interactions lead to a three-dimensional supramolecular architecture.

Phosphite, phosphine, and arsine as ligands for fac-[Re/99mTc(quin)(H2O)(CO)3]

(NO)(H2O)(CO)3] which reacts readily at room temperature with equimolar quantity of cyclohexyl isocyanide to produce the “2 + 1” mixed ligand complex fac-[Re(NO)(isc)(CO)3]. When the reaction takes place with excess of the isocyanide in refluxing toluene for prolonged time, the complexes trans-cis-[Re(NO)(isc)2(CO)2] and [Re(NO)(isc)3(CO)] are isolated by gradual replacement of the carbonyl ligands by isocyanide. All complexes were fully characterized by elemental analysis, spectroscopic methods and X-ray crystallography. These model compounds may prove useful for the development of multimodal complexes bearing more than one pharmacophore for nuclear medicine applications.