Photo-initiated Thiol-ene Click Reactions as a Potential Strategy for Incorporation of [M^I(CO)₃]⁺(M = Re,^99mTc) Complexes

Abstract

Click reactions offer a rapid technique to covalently assemble two molecules. In radiopharmaceutical construction, these reactions can be utilized to combine a radioactive metal complex with a biological targeting molecule to yield a potent tool for imaging or therapy applications. The photo-initiated radical thiol-ene click reaction between a thiol and an alkene was examined for the incorporation of [M(I)(CO)3](+) (M = Re, (99m)Tc) systems for conjugating biologically active targeting molecules containing a thiol. In this strategy, a potent chelate system, 2,2'-dipicolylamine (DPA), for [M(I)(CO)3](+) was functionalized at the central amine with a terminal alkene linker that was explored with two synthetic approaches, click then chelate and chelate then click, to determine the flexibility and applicability of the thiol-ene click reaction to specifically incorporate ligand systems and metal complexes with a thiol containing molecule. In the click then chelate approach, the thiol-ene click reaction was carried out with the DPA chelate followed by complexation with [M(I)(CO)3](+). In the chelate then click approach, the alkene functionalized DPA chelate was first complexed with [M(I)(CO)3](+) followed by the conduction of the thiol-ene click reaction. Initial studies utilized benzyl mercaptan as a model thiol for both strategies to generate the identical product from either route to provide information on reactivity and product formation. DPA ligands functionalized with two unique linker systems (allyl and propyl allyl ether) were prepared to examine the effect of the proximity of the chelate or complex on the thiol-ene click reaction. Both the thiol-ene click and coordination reactions with Re, (99m)Tc were performed in moderate to high yields demonstrating the potential of the thiol-ene click reaction for [M(I)(CO)3](+) incorporation into thiol containing biomolecules.

Oxygen insensitive thiol–ene photo-click chemistry for direct imprint lithography of oxides

“…Generally, the hydrothiolation reaction can proceed under a variety of conditions such as thermal catalytic processes, and photo-addition. [13][14][15][16] Hydrothiolation via photo-clicking is attractive as it proceeds well at room temperature reaction conditions. In a typical thiol-ene click reaction, the photogenerated electron from a photo-initiator is transferred to the thiol group to produce a thiyl radical, which adds across a carbon-carbon double bond and thus transferring the radical to the alkene.…”

Physiological Effects of Ac4ManNAz and Optimization of Metabolic Labeling for Cell Tracking

“…Therefore, it has many advantages that apply to in vivo studies. Additionally, to enhance the labeling efficiency and safety, many studies have developed advanced click reactions, such as the 'Diels-Alder' 14, 15 and 'Photo-click' 16, 17 reactions, and bio-orthogonal MRI probes 18. However, these studies only focused on the labeling step of the process; safety and the bio-physiological effects and biochemical modulation by modified glycosylation in the first step have been overlooked.…”

Synthesis and preliminary biological evaluation of a99mTc-chlorambucil derivative as a potential tumor imaging agent

“…This electrophilic moiety can form covalent adducts with double‐helical DNA, especially via reaction with N7 of guanines, either within the same strand (intrastrand) or between the 2 opposite DNA strands (interstrand) . Chlorambucil (CLB) is a chemotherapy drug classified within the nitrogen mustard group, its mechanism of action involves alkylation, and has been used for the treatment of various malignancies . Moreover, it has also been used as a template to design drugs for diagnosis and therapy of tumors …”

“…13,14 Chlorambucil (CLB) is a chemotherapy drug classified within the nitrogen mustard group, its mechanism of action involves alkylation, and has been used for the treatment of various malignancies. 15,16 Moreover, it has also been used as a template to design drugs for diagnosis and therapy of tumors. [17][18][19][20][21][22] In this study, a novel SPECT tumor imaging agent was synthesized on the basis of a design that combined the fac-[ 99m Tc(CO) 3 ] + core, CLB, and DPA.…”