Synthesis and stability of 2+1 complexes of N,N-diethylbenzoylthiourea with [MI(CO)3]+ (M = Re, 99mTc)

Hayes, Tyrone B.; Powell, A.; Barnes, Charles L.; Benny, Paul D.

doi:10.1080/00958972.2015.1071801

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…A valuable aspect for the development of rhenium-based anticancer agents is the availability of the imaging radionuclide 99m Tc. , The chemistries of technetium and rhenium are largely similar, and therefore, direct structural analogues of complexes of these metal ions can be prepared. − In the context of developing new rhenium-based anticancer agents, the corresponding 99m Tc analogues can be used as diagnostic partners to more easily ascertain pharmacokinetic properties of the parent drug candidate. Isonitrile ligands exhibit high affinity for Tc, and several Tc complexes containing ICN ligands have been reported as novel agents for biological imaging. − To evaluate the potential use of 99m Tc analogues of these TRIP complexes, we synthesized the 99m Tc analogue of the parent compound, fac -[ 99m Tc(CO) 3 (dmphen)( p tolICN)] + , called technetium tricarbonyl isonitrile polypyridyl or TTIP , using an established approach from fac -[ 99m Tc(CO) 3 (H 2 O) 3 ] + . Briefly, an aqueous solution of the 99m Tc starting material was heated at 60 °C for 1 h in the presence of a large excess of the dmphen ligand in water (pH 7).…”

Section: Resultsmentioning

confidence: 99%

Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes

et al. 2020

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The established platinum-based drugs form covalent DNA adducts to elicit their cytotoxic response. Although they are widely employed, these agents cause toxic side-effects and are susceptible to cancer-resistance mechanisms. To overcome these limitations, alternative metal complexes containing the rhenium(I) tricarbonyl core have been explored as anticancer agents. Based on a previous study (Chem. Eur. J.2019259206), a series of highly active tricarbonyl rhenium isonitrile polypyridyl (TRIP) complexes of the general formula fac-[Re(CO)3(NN)(ICN)]+, where NN is a chelating diimine and ICN is an isonitrile ligand, that induce endoplasmic reticulum (ER) stress via activation of the unfolded protein response (UPR) pathway are investigated. A total of 11 of these TRIP complexes were synthesized, modifying both the equatorial polypyridyl and axial isonitrile ligands. Complexes with more electron-donating equatorial ligands were found to have greater anticancer activity, whereas the axial ICN ligands had a smaller effect on their overall potency. All 11 TRIP derivatives trigger a similar phenotype that is characterized by their abilities to induce ER stress and activate the UPR. Lastly, we explored the in vivo efficacy of one of the most potent complexes, fac-[Re(CO)3(dmphen)(ptolICN)]+ (TRIP-1a), where dmphen = 2,9-dimethyl-1,10-phenanthroline and ptolICN = para-tolyl isonitrile, in mice. The 99mTc congener of TRIP-1a was synthesized, and its biodistribution in BALB/c mice was investigated in comparison to the parent Re complex. The results illustrate that both complexes have similar biodistribution patterns, suggesting that 99mTc analogues of these TRIP complexes can be used as diagnostic partner agents. The in vivo antitumor activity of TRIP-1a was then investigated in NSG mice bearing A2780 ovarian cancer xenografts. When administered at a dose of 20 mg/kg twice weekly, this complex was able to inhibit tumor growth and prolong mouse survival by 150% compared to the vehicle control cohort.

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Section: Resultsmentioning

confidence: 99%

Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes

et al. 2020

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“…The multicoordinate complexes had longer retention times in the blood, and the target-to-blood ratios of the three types of complexes were less than 1. Mixed monodentate isonitrile complexes, such as "4 + 1" tris(2-mercaptoethyl)-amineisocyanide complexes [41,52] and "2 + 1" dithiocarbamate/acetylacetonate-isocyanide complexes [53][54][55], can be designed. Through such a design, the coordination number is reduced, and the metabolic rate of blood and the target-to-blood ratio can be improved.…”

Section: Discussionmentioning

confidence: 99%

Radiosynthesis and Bioevaluation of 99mTc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging

Jiang,

Han,

Yin

et al. 2024

IJMS

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To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.

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“…Among monodentate ligands for implementing the 2 + 1 B approach (tethering of a biomolecule via monodentate ligand), isonitriles seem to be the best choice , owing to the favorable combination of σ-donor and π-acceptor properties (ensuring high stability of the complexes), low steric demand, good complexation kinetics, and versatility in linking to biomolecules. For example, complexes with ω-isonitrile-derivatized higher fatty acids , show promise for myocardial imaging, whereas isonitrile-derivatized lower fatty acids can serve as bifunctional molecules for tethering the 99m Tc(CO) 3 + core to diverse biomolecules. , Isonitriles as ligands for the 99m Tc(CO) 3 + core have been examined in combination with diverse bidentate ligands. ,,− As a rule, anionic bidentate ligands were chosen. It is believed that, with neutral bidentate ligands, the sixth coordination site in the tricarbonyl complexes will be occupied by the chloride ion necessarily present in the reaction medium, and its replacement by a monodentate ligand will be hindered.…”

Section: Introductionmentioning

confidence: 99%

2 + 1 Tricarbonyl Complexes of Technetium(I) with a Combination of N,N-Bidentate Ligands and Ethyl Isocyanoacetate: How Strong Is the Interfering Effect of Chloride Ions on Their Formation?

Sidorenko,

Miroslavov,

Tyupina

et al. 2023

Inorg. Chem.

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Technetium(I) 2 + 1 tricarbonyl complexes with a combination of N,N-bidentate ligands (2,2′-bipyridine, bipy; 1,10phenanthroline, phen) and ethyl isocyanoacetate were prepared and characterized by NMR, IR, UV/visible, and luminescence spectroscopies and by high-performance liquid chromatography (HPLC). The crystal structures of [ 99 Tc(CO) 3 (bipy)(CNCH 2 COOEt)](ClO 4 ) (in the form of a solvate with 0.5CH 2 Cl 2 ) and [ 99 Tc(CO) 3 (phen)-(CNCH 2 COOEt)](ClO 4 ) (in the form of an adduct with an outersphere phen molecule) were determined by single-crystal X-ray diffraction. To evaluate the interfering effect of chloride ions on the formation of the 2 + 1 complexes, the kinetics of the replacement of labile monodentate ligand X in the complexes [MX(CO) 3 (N ∧ N)] (M = Re, 99 Tc; N ∧ N = bipy, phen; X = Cl − , ClO 4 − ) by CNCH 2 COOEt in ethanol were compared. The 99 Tc bipy complexes with X = ClO 4 − (according to the IR data, perchlorate anion in ethanol is displaced from the coordination sphere by the solvent molecule) and X = Cl − are characterized by close ligand replacement rates. In the case of the 99 Tc complexes with phen and Re complexes with both phen and bipy, the chloride complexes are appreciably less reactive than the chloride-free complexes. The technetium complexes are considerably more reactive in ligand replacement than their rhenium analogues. In the chloride-containing medium (saline), the complex [ 99m Tc(CO) 3 (bipy)(CNCH 2 COOEt)] + can be prepared under the conditions acceptable for nuclear medical applications, although higher isonitrile concentrations are required as compared to the chloride-free system.

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Synthesis and stability of 2+1 complexes of N,N-diethylbenzoylthiourea with [M^I(CO)₃]⁺ (M = Re, ^99mTc)

Cited by 8 publications

References 48 publications

Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes

Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes

Radiosynthesis and Bioevaluation of 99mTc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging

2 + 1 Tricarbonyl Complexes of Technetium(I) with a Combination of N,N-Bidentate Ligands and Ethyl Isocyanoacetate: How Strong Is the Interfering Effect of Chloride Ions on Their Formation?

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