*2.4. Vitamins*

Anna Yu. Bogdanovab et al. presented the cyanocobalamin (B12) as a biocompatible B12-ReII(CO)2 scaffold for CORMats (Figure 17) [150]. They incorporated the *cis*-*trans*-[ReII(CO)2Br2]0 core having 17e- dicarbonyl complexes. This research also elaborated that ReCORM-1 is compatible with B12 for pharmaceutical applications, and the obtained cobalamin conjugates are also feasible with aqueous aerobic media. Interestingly, after CO releasing, metal degradation is not involved in toxicity due to the exclusive configuration and metal oxidation of ReO4- generation.

**Figure 17.** B12-ReII(CO)2 CORMats conjugate: (**A**) B12-ReCORM-2; (**B**) B12-ReCORM-4.

The most promising anticancer drug agen<sup>t</sup> is a macromolecular conjugate. The HO-1 and transcription factor Nrf2 are the prime parameters to provide resistance against inflammation and oxidative stress disease. In this analogy, biliverdin is the enzymatic activity of HO-1, while CO directs the therapeutic exploitation. Roberta Foresti et al. found that hybrid molecules were simultaneously involved in the CO liberation and Nrf2 activation [151]. The newly developed CORMats termed as hybrid-CORMats (HY-CORMats) is shown in Figure 18.

**Figure 18.** Synthesis route of hybrid CORMats: (**A**) HY-CORMats-1; (**B**) HY-CORMats-2.

After synthesizing the HY-CORMats, researchers further interrogated the biological activities and described the HO-1 expression along with the nuclear accumulation of Nrf2 and showed viability in different cell types (Scheme 4).

**Scheme 4.** The hybrid CORMats (HY-CORMats-1) has a CO moiety for various anti-inflammatory, antioxidant actions and induced nuclear accumulation of Nrf2.

A. Pamplona's group coordinated the galactose with a central metal to synthesize a polyhydric-containing water-soluble CORMats [RuCl2-thiogalacto-pyranoside(CO)3] (ALF492) through Sulphur bond (Figure 19) [152]. The Sulphur bond coordination of the galactose ligand with the central metal increases the water solubility and biocompatibility. This compound also exhibited the appropriate drug-like properties. The presence of the galactose ligand increases the specificity of liver glycoprotein. A myoglobin study was used to monitor the CO release kinetic profile. The target selectivity of ALF492 can be well administrated. Significantly, when ALF492 is mixed with the antimalarial drug artesunate, ALF492 responds to the effective adjuvant treatment for cerebral malaria. Collectively, this marks the outstanding potential of ALF492 in the treatment of falciparum malaria.

**Figure 19.** Galactose chelated three carbonyl ruthenium complexes.

The CC Romao group synthesized the molybdenum-based water-soluble release molecule Mo(CO)3(CNCR'R"CO2H)3 (R'=R"=H, ALF795) (R'=R"=CH3, ALF794) (Figure 20) [153]. Myoglobin experiments have shown that compounds were stable and did not decompose in an aerobic aqueous solution for at least 1 hr. ALF794 is less toxic and suitable for drug-like properties. It can deliver CO to acetamido phenol-induced liver in mice with acute liver failure. After 5 min, intravenous injection, the ratio of ALF794 in liver/blood and liver/kidney were reported at 5.27 and 12.58, respectively and ALF795 liver/blood and liver/kidney ratios were observed at 0.33 and 0.50, respectively.

**Figure 20.** β-isocyanate coordinated molybdenum carbonyl complexes.
