## 2 Metal-Based Carbohydrate Drug Conjugates
In this context, [PERSON] and colleagues have reported the synthesis of five-coordinated trigonal bipyramidal Pt(II) complexes **2** and **3**, which have shown high reactivity in physiological conditions (Figure 1B) [50]. In fact, the _trans effect_ of the methyl group in axial position enables the easy substitution of pyridine or triazole ligands. On the contrary, square planar Pt(II) complexes **4** and **5** are very robust even in solutions with different ratios of physiological solution and DMSO. Notably, their lower reactivity can be explained by the presence of a weaker _trans_-labilizing ligand such as phenanthroline in _trans_ to pyridine or triazole. The biological results have shown a superior cytotoxicity on MCF-7 and A431 cancer cell lines of five-coordinated Pt(II) complexes **2** and **3** with respect to the four-coordinated Pt(II) complexes **4** and **5**. The latter have shown DNA intercalation as confirmed by the ethidium bromide assay using calf-thymus DNA (ctDNA) as well as the activation of caspases  
3 and 9 [50]. Moreover, complexes **2** and **3** exhibited a lower cytotoxicity towards H9c2 and HaCaT normal cell lines, thus suggesting a certain in vitro selectivity. Interestingly, a lower cytotoxicity was noticed in the case of glucose derivatives with respect to their acylglucose congeners. Octahedral Pt(IV) complexes are considered excellent prodrugs and valid alternatives to classical square planar Pt(II) complexes. In Figure 1C, the general structures of Pt(II) and  
Figure 1: Pt complexes synthesized by [PERSON] group. (**A**) Limit forms of Pt(0) complex; (**B**) Structures of Pt(II) complexes, counterions are omitted; (**C**) Structures of Pt(II) and Pt(IV) complexes. Pt(IV) complexes bearing carbohydrate-based NHC ligands are reported. The coordination sphere of platinum is completed with phenanthroline, methyl and ethylene (for Pt(II) species) ligands [51]. Pt(II)-NHC complexes **6a-c** are sufficiently stable under physiological conditions. However, in the presence of stronger coordinating solvents (e.g., DMSO) the release of ethylene and phenanthroline was observed. On the contrary, Pt(IV)-NHC complexes **7a-c** displayed a lower stability in aqueous solution, since the presence of their azolium salts was noticed by NMR studies. Additionally, in these categories of compounds, the key role of the type of glycosidic substituent used was confirmed. In particular, the presence of galactose renders these platinum complexes inactive towards MCF-7 and A431 cancer cells. At the same time, Pt(II)-NHC complexes exhibited a greater cytotoxicity compared to their Pt(IV)-NHC congeners (IC\({}_{50}\) > 125 \(\upmu\)M). As expected, none of the compounds tested acts via DNA double-strain (dsDNA) intercalation. However, a direct interaction with both double-strain DNA and single-strain DNA was detected by ESI-MS. In addition, stability studies in the presence of a few selected proteins such as human serum albumin (HSA) and hen egg white lysozyme (HEWL) suggested a potential stable interaction [51]. Moving to the gold chemistry, neutral Au(I) complexes bearing NHCs ligands are usually thioredoxin reductase inhibitors (TrxR), a selenoprotein belonging to the Trx system, which is located in the mitochondria. On the contrary, cationic Au(I) biscarbene complexes usually interact with DNA, in particular with G-quadruplex DNA structures [52; 53; 54; 55; 56]. Taking advantage of the easy _click reaction_, NHC ligands bearing a glycosidic triazole moiety can be synthesized and directly coordinated to gold [57]. More specifically, neutral gold-NHC complexes **8a-c**, depicted in Figure 2A, present the same glycosidic-NHC but different halides. The compounds are quite stable in polar solvents (e.g., DMSO, DMSO-H\({}_{2}\)O and Acetone-H\({}_{2}\)O solutions). However, traces of cationic biscarbene species [Au(NHC\({}_{2}\))]\({}^{+}\) can be observed, especially in the NHC-Au-Cl complex.