Synthesis and evaluation of new mixed "2 + 1" Re, 99m Tc and 186 Re tricarbonyl dithiocarbamate complexes with different monodentate ligands.

Autor: Shegani A; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece; Research Reactor Center, University of Missouri, Columbia, MO 65211, United States., Ischyropoulou M; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Roupa I; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Kiritsis C; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Makrypidi K; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Papasavva A; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Raptopoulou C; Institute of Nanoscience and Nanotechnology, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Psycharis V; Institute of Nanoscience and Nanotechnology, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Hennkens HM; Research Reactor Center, University of Missouri, Columbia, MO 65211, United States; Department of Chemistry, University of Missouri, Columbia, MO 65211, United States., Pelecanou M; Institute of Biosciences & Applications, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Papadopoulos MS; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece., Pirmettis I; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15310 Athens, Greece. Electronic address: ipirme@rrp.demokritos.gr.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2021 Oct 01; Vol. 47, pp. 116373. Date of Electronic Publication: 2021 Aug 19.
DOI: 10.1016/j.bmc.2021.116373
Abstrakt: A series of "2 + 1" mixed ligand tricarbonyl complexes of the general formula fac-[Re/ 99m Tc/ 186 Re(CO) 3 (DDTC)(L)] containing diethyldithiocarbamate (DDTC) as a monoanionic bidentate ligand and a series of monodentate ligands L was synthesized, characterized and evaluated. The impact of ligand L on the radiochemical yield (RCY) and biodistribution of the final compounds was also investigated. DDTC and the appropriate L ligand [cyclohexyl isocyanide (cisc), tert-butyl isocyanide (tbi), triphenylphosphine (PPh 3 ), methyldiphenylphosphine (PPh 2 Me), triphenylarsine (AsPh 3 ), imidazole (im), and 4-aminopyridine (4AP)] readily reacted in equimolar amounts with the [Et 4 N] 2 [Re(CO) 3 Br 3 ] precursor to afford fac-[Re(CO) 3 (DDTC)(cisc)], Re1, fac-[Re(CO) 3 (DDTC)(tbi)], Re2, fac-[Re(CO) 3 (DDTC)(PPh 3 )], Re3, fac-[Re(CO) 3 (DDTC)(PPh 2 Me)], Re4, fac-[Re(CO) 3 (DDTC)(AsPh 3 )], Re5, fac-[Re(CO) 3 (DDTC)(im)], Re6 and fac-[Re(CO) 3 (DDTC)(4AP)], Re7, complexes in high yields (>80%). All Re complexes were fully characterized by IR, NMR, and in addition Re4, Re5, and Re7 with X-ray crystallography. Analogous reactions as performed with Re were subsequently explored on the 99m Tc and 186 Re-tracer levels using the corresponding fac-[ 99m Tc/ 186 Re(CO) 3 (H 2 O) 3 ] + precursor. Complexes 99m Tc1 - 99m Tc5, 186 Re1 and 186 Re3 were obtained in high radiochemical yield (>91%), while the complexes 99m Tc6, 99m Tc7 and 186 Re7 formed with radiochemical yields of 55%, 28%, and 75%, respectively. The 99m Tc and 186 Re-complexes were characterized by comparative HPLC analysis using the analogous Re complexes. During histidine and cysteine challenge experiments at 37 °C through 6 h, complexes 99m Tc1 - 99m Tc5 remained > 92% stable, while complexes 99m Tc6 and 99m Tc7 remained only 8% stable through 3 h. Similar studies for 186 Re-complexes showed that 186 Re1 and 186 Re3 remained > 95% stable for up to 48 h, while 186 Re7 had decreased to 7% after 3 h. LogD 7.4 data of 99m Tc1 - 99m Tc5, 186 Re1, and 186 Re3 complexes, which ranged from 2.59 to 3.39, suggested high lipophilicity. Biodistribution studies in healthy Swiss albino mice showed hepatobiliary excretion for 99m Tc1, 99m Tc2, and 99m Tc4, fast blood clearance for 99m Tc4, while high liver uptake and retention for 99m Tc3 and 99m Tc5 were measured. Moreover, 99m Tc2 showed high accumulation in the lungs with sustained retention (52.80% ID/g at 4 h p.i.) and significant brain uptake at 2 min p.i. (1.89% ID/g). The study showed the great influence of monodentate ligand in the synthesis and biodistribution of the mixed ligand complexes.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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