An innovative and efficient route to the synthesis of metal-based glycoconjugates: proof-of-concept and potential applications

Abstract

With a view to developing more efficient strategies to the functionalization of metallodrugs with carbohydrates, we here report on an innovative and efficient synthetic route to generate gold(iii) glycoconjugates in high yields and purity. The method is based on the initial synthesis of the zinc(ii)-dithiocarbamato intermediate [Zn(SSC-Inp-GlcN)] (Inp = isonipecotic moiety; GlcN = amino-glucose) followed by the transfer of the glucoseisonipecoticdithiocarbamato ligand to the gold(iii) center via transmetallation reaction between the zinc(ii) intermediate and K[AuBr] in 1 : 2 stoichiometric ratio, yielding the corresponding glucose-functionalized gold(iii)-dithiocarbamato derivative [AuBr(SSC-Inp-GlcN)]. No protection/deprotection of the amino-glucose scaffold and no chromatographic purification were needed. The synthetic protocol was optimized for glucose precursors bearing the amino function at either the C or the C position, and works in the case of both α and β anomers. The application of the synthetic strategy was also successfully extended to other metal ions of biomedical interest, such as gold(i) and platinum(ii), to obtain [Au(SSC-Inp-GlcN)(PPh)] and [Pt(SSC-Inp-GlcN)], respectively. All compounds were fully characterized by elemental analysis, mid- and far-IR, mono- and multidimensional NMR spectroscopy, and, where possible, X-ray crystallography. Results and potential applications are here discussed.

Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents

“…reported the synthesis of a series of Au(III) dithiocarbamate glycoconjugates, focusing on the development of a straightforward and versatile (they also reported zinc and platinum derivatives) synthetic pathway and a detailed chemical characterization. However, no in vitro/vivo data were reported for these complexes [117] …”

New Bioconjugated Technetium and Rhenium Folates Synthesized by Transmetallation Reaction with Zinc Derivatives

“…The obtained zinc complex al the formation of the bioconjugated complex with the desired transition metal by a the simple transmetallation reaction. It should be highlighted that this compound ready been employed by another research group for preparing bioconjugated go plexes [11], which is a very different goal to our research objectives. Our approach is focused on preparing of Tc-99m complexes for radiopharma applications.…”

“…Using Zndithiocarbamates is useful for this goal because they show very low solubilities in water, so the concentration of unlabeled biomolecule stays very low in the reaction medium (water) and the insoluble Zn-dithiocarbamate can be easily removed by filtration. In addition, Zn-dithiocarbamates are useful compounds for transmetallation reactions, a property that has been reported for different applications [4][5][6]10,11,16].…”

Conjugating Biotin to Ruthenium(II) Arene Units via Phosphine Ligand Functionalization

“…These Ru(III) compounds exhibit lower toxicities and side‐effects than the clinically approved Pt(II) drugs, attributed to in situ reduction and activation of Ru(III) to Ru(II) species in the tumour environment.2 ,[3] However, a key limitation of all of these drugs is that they do not efficiently target tumours. Consequently, efforts have been devoted to attaching targeting groups to metal‐based drugs to enhance their uptake into cancer cells, by exploiting the different characteristics of cancerous and normal cells . Therefore, various small molecule targeting groups have been investigated, including folic acid, riboflavin and sugars.…”

“…Therefore, various small molecule targeting groups have been investigated, including folic acid, riboflavin and sugars. [4a] In this regard, biotin (see Figure ) is a vitamin whose uptake into cancer cells is related to sodium‐dependent multi‐vitamin transporter (SMVT), encoded by the SLC5A6 gene which is overexpressed in certain cancer cell lines (e.g. breast, lung, ovarian, and renal cancer cells) .…”