Protein engineering – artificial metalloenyzmes

bioorthogonal reactions ; PAMAM dendrimer; papain; transfer hydrogenation; ruthenium; metallocarbonyl complex; bioconjugation; IR spectroscopy


Electrochemical Characterization of the Artificial Metalloenzyme Papain-[ (h6-Arene)Ru(1,10-Phenanthroline)Cl]+. Nováková Lachmanová, Š. ; Pospíšil, L. ; Šebera, J. ; Talbi, B. ; Salmain, M. ; Hromadová, M. J. Electroanal. Chem. 2020, 859, 113882 ;

“Electrochemical properties were studied for [ (η6-arene)Ru(1,10-phenanthroline)Cl]Cl (arene = C6H5(CH2)2NHCOCH2Cl) organometallic complex 1, protein Papain PAP and its conjugate with organometallic complex 1-PAP.“

Inverse Electron-Demand Diels-Alder (IEDDA) Bioorthogonal Conjugation of Half-Sandwich Transition Metallocarbonyl Entities to a Model Protein. Jamroz, D. ; Fischer-Durand, N. ; Palusiak, M. ; Wojtulewski, S. ; Jarzyński, S. ; Stępniewska, M. ; Salmain, M. ; Rudolf, B. Appl. Organomet. Chem. 2020, 34, e5507 ;

“Novel transition metallocarbonyl complexes carrying a norbornene or an oxanorbornene group were synthesized by [4 + 2] cycloaddition between the organometallic maleimide dienophiles and cyclopentadiene or furan, respectively. The (oxa)norbornene groups further provided convenient chemical reporters to carry out inverse electron demand Diels-Alder (iEDDA) reactions with tetrazine derivatives. Detailed kinetic studies with a model tetrazine revealed that faster rates of reaction were determined with both isomers of the oxanorbornene complex with respect to the norbornene complexes. Eventually, incorporation of metallocarbonyl entities into bovine serum albumin equipped with tetrazine handles was achieved as shown by IR spectroscopy of the protein conjugates.”


‘Clickable’ Cyclopentadienyl Iron Carbonyl Complexes for Bioorthogonal Conjugation of Mid-Infrared Labels to a Model Protein and PAMAM Dendrimer. Fischer-Durand, N. ; Lizinska, D. ; Guérineau, V. ; Rudolf, B. ; Salmain, M. Appl. Organomet. Chem. 2019, 33, e4798 ;

“Two cyclopentadienyl iron dicarbonyl (Fp) complexes carrying a terminal or a strained alkyne handle were synthesized and their reactivity was examined towards a model protein and poly (amidoamine) (PAMAM) dendrimer, both carrying azido groups. While the copper (I)-catalysed azide-alkyne cycloaddition (CuAAC) proceeded smoothly with the terminal alkyne metallocarbonyl derivative, labelling by strain-promoted azide-alkyne cycloaddition (SPAAC) was less successful in terms of final coupling ratios. Infrared spectral characterization of the bioconjugates showed the presence of two bands in the 2000 cm−1 region, owing to the stretching vibration modes of the carbonyl ligands of the Fp entities.”


Embedding a Ruthenium-Based Structural Mimic of the [Fe]-Hydrogenase Cofactor into Papain. Barik, C. K. ; Ganguly, R. ; Li, Y. ; Przybylski, C. ; Salmain, M. ; Leong, W. K. Inorg. Chem. 2018, 57, 12206–12212 ;

“We describe the synthesis of the ruthenacyclic carbamoyl complexes [Ru(2-NHC(O)C5H3NMe)(CO)2(o,o-Me2-C6H3S)(L)] (L = H2O or MeCN), which have a labile water or acetonitrile ligand at their sixth coordination sites. Steric bulk around the ruthenium center is essential in preventing isomerization and dimerization, and embedding within papain can be achieved via coordination of its sole free cysteine residue. The observed chemistry parallels that of the natural [Fe]-hydrogenase.”

Proteins as Macromolecular Ligands for Metal-Catalysed Asymmetric Transfer Hydrogenation of Ketones in Aqueous Medium. Cázares-Marinero, J.d.J. ; Przybylski, C. ; Salmain, M. Eur. J. Inorg. Chem. 2018, 2018, 1383–1393 ;

“Dative assembly of half-sandwich ruthenium, rhodium or iridium complexes to beta-lactoglobulin or lysozyme gave biohybrids that catalysed the asymmetric transfer hydrogenation of ketones with up to 86 % ee. Complementary investigations indicated involvement of His146 of beta-lactoglobulin in ruthenium coordination.”

Crystallographic Evidence for Unexpected Selective Tyrosine Hydroxylations in an Aerated Achiral Ru–Papain Conjugate. Cherrier, M. V. ; Amara, P. ; Talbi, B. ; Salmain, M. ; Fontecilla-Camps, J. C. Metallomics 2018, 10, 1452–1459 ;

“The X-ray structure of an aerated achiral Ru–papain conjugate has revealed the hydroxylation of two tyrosine residues found near the ruthenium ion. The most likely mechanism involves a ruthenium-bound superoxide as the reactive species responsible for the first hydroxylation and the resulting high valent Ru(IV)[double bond, length as m-dash]O species for the second one.”


Supramolecular Anchoring of NCN-Pincer Palladium Complexes into a β-Barrel Protein Host : Molecular-Docking and Reactivity Insights. Pocquet, L. ; Vologdin, N. ; Mangiatordi, G. F. ; Ciofini, I. ; Nicolotti, O. ; Thorimbert, S. ; Salmain, M. Eur. J. Inorg. Chem. 2017, 2017, 3622–3634 ;

“Prochiral NCN-pincer palladium(II) complexes of hemilabile ligands and a long aliphatic chain were shown to insert into bovine β-lactoglobin, as assessed by CD spectroscopy and molecular-docking calculations. Adjunction of H-bond donor substituents gave more-stable supramolecular assemblies. These constructs catalyzed aldol condensations, affording, in some cases, the less-favorable cis product.”