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Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (99mTc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new “4 + 1” mixed-ligand ReIII- and 99mTcIII-complexes of the general formula [99mTc][Tc(NS3)(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS3) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand. The quinazoline isocyanide derivatives 4a-d were prepared in two steps and reacted with the [Re(NS3)PMe2Ph] precursor leading to the final complexes 5a-d in high yield. All compounds were characterized by elemental analysis, IR, and NMR spectroscopies. In vitro studies, for their potency to inhibit the cell growth, using intact A431 cells indicate that the quinazoline derivatives 4a-d and the Re complexes 5a-d significantly inhibit the A431 cell growth. In addition, the EGFR autophosphorylation study of complex 5b shows an IC50 value in the nanomolar range. The corresponding “4 + 1” 99mTc-complexes 6a-d were prepared by employing the [99mTc]TcEDTA intermediate and the appropriate monodentate 4a-d in a two-step synthetic procedure with a radiochemical yield (RCY) from 63 to 77 % and a radiochemical purity (RCP) > 99 % after HPLC purification. Their structures have been established by HPLC comparative studies using the well-characterized Re-complexes 5a-d as reference. All 99mTc-complexes remain stable for at least 6 h, and their logD7.4 values confirmed their anticipated lipophilic character. Biodistribution studies in healthy Swiss albino mice of 99mTc-complexes showed hepatobiliary excretion and initial fast blood clearance. Complex 6b was also tested in Albino SCID mice bearing A431 tumors and showed rapid tumor uptake at 5 min (2.80 % ID/g) with a moderate tumor/muscle ratio (2.06) at 4 h p.i. The results encourage further investigation for this type of 99mTc-complexes as single-photon emission computed tomography (SPECT) radio agents for imaging tumors overexpressing EGFR. © 2022 Elsevier Ltd

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A series of "2 + 1" mixed ligand tricarbonyl complexes of the general formula fac-[Re/

In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)(3)(LL2)-L-1] complexes (M = Re, Tc-99m) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand ((LH)-H-1) and a series of monodentate ligands (L-2). First, fac[Re(CO)(3)(PO)(H2O)], 1, was synthesized by reaction of POH and [Et4N](2)[Re(CO)(3)Br-3] in equimolar amounts in MeOH at room temperature. Interestingly, with excess of POH this reaction afforded fac-[Re(CO)(3)(PO)(POH)], 2, with POH operating both as a bidentate and as a monodentate ligand. Owing to the presence of the labile aqua ligand, which can be readily replaced by various monodentate ligands, 1 was further used as a precursor to generate a small library of the desired fac-[M(CO)(3)(LL2)-L-1] complexes. Specifically, by reaction of triphenylphosphine (PPh3), imidazole (im), pyridine (py), cyclohexyl isocyanide (cisc), and tert-butyl isocyanide (tbi), the following products were readily obtained in excellent yields (92%-95%): fac-[Re(CO)(3)(PO)(PPh3)], 3, fac-[Re(CO)(3)(PO)(im)], 4, fac-[Re(CO)(3)(PO)(py)], 5, fac-[Re(CO)(3)(PO)(CiSc)], 6, and fac-[Re(CO)(3)(PO)(tbi)], 7. All compounds were fully characterized by elemental analysis, IR and NMR spectroscopies, and electrospray ionization(+) mass spectrometry. Their solid-state structure was elucidated by X-ray crystallography. Of considerable interest is the fact that the corresponding 2'-7' were easily accessible at the Tc-99m-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L-2 with fac-[Tc-99m(CO)(3)(H2O)(3)] in aqueous MeOH, as verified by comparative chromatographic methods adopting dual photo and radiometric detection modes. The high stability displayed by all Tc-99m complexes during histidine and cysteine challenge assays underscored the suitability of the fac-[M(CO)(3)(PO)L-2] system for radiopharmaceutical development purposes.

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., In the title compound, [Re(C10H6NO2)(CO)3{As(C6H5)3}], the coordination environment of ReI is that of a distorted octa­hedron. Three coordination sites are occupied by three carbonyl groups in a facial arrangement and the remaining three sites by tri­phenyl­arsane and deprotonated quinaldic acid in As-mono- and N,O-bidentate fashions, respectively. In the crystal, the complexes are linked through weak C—H⋯O hydrogen bonds, forming a three-dimensional network. It worth noting that, as far as we know, this complex is the first ReI tri­phenyl­arsane tricarbonyl compound to be reported.