Neovascularization Effects of Carbon Monoxide Releasing Drugs Chemisorbed on Coscinodiscus Diatoms Carriers Characterized by Spectromicroscopy Imaging

Abstract

Silica microparticles made of diatomaceous earth have become particularly attractive materials for designing drug delivery systems. In order to investigate the use of natural diatoms as drug scaffolds for carbon monoxide releasing molecules (CORMs), we evaluated the chemisorption of the cis-[Re(CO)2Br4]2− complex (ReCORM-2) and its vitamin B12 derivative (B12-ReCORM-2) on Coscinodiscus frustules by 3D FT-IR spectroscopic imaging, and the drugs’ neovascularization effects in vivo in the zebrafish (Danio rerio) model. By mapping the symmetric Re-C≡O υ(CO) stretching vibration of the CORMs in the 2000 cm−1 region, we found that the drugs are mostly localized at the girdle band of the diatom frustule. Both ReCORM-2 and B12-ReCORM-2 retain their CO-releasing ability when chemisorbed on the diatoms. When applied in vivo at doses ≥25 µM, the molecules markedly reduced intersegmental and subintestinal vessels development in zebrafish, revealing high anti-angiogenic potential. In addition, diatom frustules did not provoke any toxic in vivo response in the zebrafish embryos, including inflammation. Overall, our results indicate that: (1) CORMs chemisorbed on diatom frustules retain their CO-releasing abilities; (2) both CO-releasing molecules show a concentration-dependent effect on the neovascularization in developing zebrafish; (3) silicate frustules are not toxic and could be used as CORMs drug carriers.

Efficient Direct Nitrosylation of α-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release

“…Given the apparent affinity of the fac-[Re(CO)2(NO)] 2+ core for π-donors, we reasoned that fac-[Re I (CO)3(N-N)OR] species might offer us a different chemical approach for the design of an efficient synthetic strategy to fac-[Re(CO)2(NO)(N-N)L] 2+ compounds. Therefore, we decided to test the reaction of fac-[Re I (CO)3(N-N)OR], where OR = OH − , benzoate (10), 2-(4-bromophenyl)acetate (11).…”

“…Our group has been interested in the development of the chemistry of tri- and dicarbonyl rhenium complexes for applications in different medicinal fields [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], including their use as antibacterial agents. We recently reported studies on the antimicrobial properties of families of rhenium diimine (N-N) complexes and found several complexes of general formula fac -[Re I (CO) 3 (N-N)L] + (L = pyridine, py, type-ligand), showing low to no toxicity in vivo and potent in vitro and in vivo activity against infection of clinically relevant bacteria (MRSA) and fungi ( Candida species) [ 19 , 20 ].…”

Aerobically stable and substitutionally labile α-diimine rhenium dicarbonyl complexes

“…43,44 Our group has been interested in the chemistry of 18-and 17electron fac-[Re I (CO) 3 ] + and cis-[Re II (CO) 2 ] 2+ species for their potential use in medicinal chemistry, particularly as anticancer [45][46][47][48] and antibacterial agents 26,49,50 and CO-releasing molecules respectively. [51][52][53][54] While abundant literature is available for the biological effects of Re(I) tricarbonyl complexes, very little is known for corresponding Re(I) dicarbonyl species. We, therefore, set out to establish synthetic procedures that would allow accessing the latter core.…”

Combatting AMR: a molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection

“…42 Our groups are also interested in the chemistry of 18-and 17-electron fac-[Re I (CO) 3 ] + and cis-[Re II (CO) 2 ] 2+ species for their potential use in medicinal chemistry, as anticancer, [44][45][46] CO-releasing and antibacterial agents. [47][48][49] Recently, we reported a study on the antimicrobial properties of a series of 3arylcoumarin rhenium complexes and found that about half of the species investigated exhibit potent in vitro and in vivo activity against MRSA with MICs in the nanomolar range (ca. 350-700 nM in vivo).…”