Sonogashira and “Click” reactions for the N-terminal and side-chain functionalization of peptides with [Mn(CO)3(tpm)]+-based CO releasing molecules (tpm = tris(pyrazolyl)methane)

Abstract

A recently identified photoactivatable CO releasing molecule (CORM) based on [Mn(CO)(3)(tpm)](+) was conjugated to functionalized amino acids and model peptides using the Pd-catalyzed Sonogashira cross-coupling and the alkyne-azide 1,3-dipolar cycloaddition ("Click reaction"). Both were found to be fully compatible with all functional groups present. The CORM-peptide conjugates were isolated in reasonable yield and high purity, as indicated by IR spectroscopy, ESI mass spectrometry and RP-HPLC. The myoglobin assay was used to demonstrate that they have CO release properties identical those of the parent compound. This work thus opens the way for a targeted delivery of CORMs to cellular systems.

Electronic Influences on the Stability and Kinetics of Cp* Rhodium(III) Azide Complexes in the iClick Reaction with Electron‐Poor Alkynes

“…[12][13][14] In bioorganic chemistry, a wide range of reactions has been explored in that context, the copper-catalyzed (CuAAC) [15,16] and strain-promoted (SPAAC) [17] azide-alkyne cycloaddition reactions, as well as the Staudinger and tetrazine [18] ligations, being the most widely utilized. While these reactions can also be applied to the ligand periphery of metal complexes, [19][20][21] the utilization of metal-inherent functionality with reactions directly taking place in the inner metal coordination sphere has been much less explored for bioconjugation studies. On the basis of the known reactivity of metal azide complexes with electron-poor alkynes, [22,23] in particular that of linear gold(I) azide compounds, [24][25][26][27][28][29][30] some bioactive dendrimer and peptide conjugates were prepared in recent years by using such inorganic click (iClick) reactions.…”

Diacetylplatinum(II) and ‐platinum(IV) Complexes Bearing κ2‐ and κ3‐Coordinated Tris(pyrazolyl)methane Ligands: Investigations on the Synthesis, Fluxionality, and Reactivity in Relation to the Substitution Pattern of the Ligands

“…In [Pt(COMe) 2 H{(pz) 3 CH}]Cl (3a), the δ H of the methine proton of the HC(pz) 3 ligand was found at much lower field (δ H = 12.39 ppm) relative to the free ligand (δ H = 8.41 ppm) [21] and to the corresponding diacetylplatinum(II) complex 4a (δ H = 9.14 ppm), whereas the analogous compound 5a with triflate as counterion exhibits this resonance at δ = 10.17 ppm. The same tendency was also observed for the methylplatinum(IV) complexes [Pt(COMe) 2 Me-{(pz) 3 3 CH}] (δ H = 9.27 ppm).…”

A Photoactive Carbon‐Monoxide‐Releasing Protein Cage for Dose‐Regulated Delivery in Living Cells

“…However, there have been few reports on the effects of CO released into cells and tissues by light irradiation of the photoactive CORMs. [36][37][38] To adapt the reactivities of photoactive CORMs to cellular environments,i ti se ssential to design scaffolds with improved biocompatibility such as proteins because several proteins have great potential to deliver CORMs. [39][40][41][42][43] In this work, we developed ap hotoactive CO-releasing protein based on ferritin (Fr), an iron storage protein.…”