Glycoconjugated Rhenium(I) and 99m‐Technetium(I) Carbonyl Complexes from Pyridyltriazole Ligands Obtained by “Click Chemistry”

Abstract

A series of pyridyltriazole ligands containing sugar moieties have been prepared by copper(I)‐mediated 1,3‐dipolar cycloaddition (“click” reaction) of azides functionalized with D‐glucose, D‐galactose, D‐mannose, D‐xylose as well as D‐maltose residues, and 2‐ethynylpyridine as alkyne. The peracetylated saccharide residues as well as their water‐soluble deprotected derivatives were treated with Re(CO)5Cl to obtain the corresponding mononuclear rhenium(I) carbonyl complexes [LRe(CO)3Cl]. For comparison, one ReI complex bearing a tert‐butylbenzyl residue instead of a sugar moiety as well as two dinuclear rhenium complexes derived from a branched ligand containing two pyridyltriazole units were prepared. The structure and integrity of the ligands and complexes was established by NMR, IR, UV/Vis and fluorescence spectroscopy, mass spectrometry, and by elemental analysis. Coordination of the metal ion occurred by both the pyridyl nitrogen atoms and one of the triazole nitrogen atoms. Upon treatment with an excess of histidine, the ReI complexes were stable for only 2.5 h. After a longer period (24 h) ligand exchange was detected by HPLC measurements. In contrast, a complex labeled with 99mTc was found to be stable for up to 24 h against an excess of histidine. Cytotoxicity was screened for all ReI complexes against HepG2 cells using a concentration of 100 μM. All sugar‐functionalized complexes were found to be nontoxic, except for the complex derived from the pyridyl (tert‐butylbenzyl)‐triazole, which exhibited remarkable toxicity.

Photophysics and photochemistry of 1,2,3-triazole-based complexes

“…[8] Several reports, most notably those from the group of Policar, have made use of the pytz architecture and its close structural analogues in the design of Re(I) complexes towards multi-modal biological imaging agents. These include complexes bearing amides, [46] hexanoylglutamine, [47] short peptides, [48] sugars, [49] azidoalkyl [50] and alkyl moieties appended to the triazole ring. [51] Interestingly, in the case of the latter, the long alkyl chain leads to increased emission intensity in aqueous solutions due to folding of the chain around the rhenium core providing protection from solvent related quenching interactions.…”

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

“…Similarly, glycoconjugates of mononuclear Re (I) carbonyl complexes with pyridyltriazole ligands have been prepared with coordination of the metal ion by both pyridyl and triazol nitrogen atoms. All sugar-functionalized complexes were found to be nontoxic against HepG2 cells at concentration of 100 μM, except for the complex derived from the pyridyl (tert-butylbenzyl)-triazole, which exhibited remarkable toxicity [140].…”

Towards dual SPECT/optical bioimaging with a mitochondrial targeting, 99mTc(i) radiolabelled 1,8-naphthalimide conjugate

“…Firstly, the methylene linkers of the dipicolylamine unit shift upon coordination and become diastereotopic with an observed coupling around 16 Hz. 28 The aliphatic protons of the linker unit are also mildly shifted in the complex versus the ligand. The general pattern amongst the aromatic proton resonances is retained upon formation of the complex.…”

“…All isotopes of technetium are radioactive, and so natural rhenium is commonly used as a chemical analogue 28 to allow the synthetic and purification protocols to be optimised prior to the use of a radionuclide. The corresponding tricarbonyl Re(I) complexes were isolated by reacting 29 the precursor compounds with fac-[Re(CO) 3 (MeCN) 3 ]BF 4 to yield fac-[Re(CO) 3 (L)] BF 4 as air stable solids.…”