Exploring the Strength of the H‐Bond in Synthetic Models for Heme Proteins: The Importance of the N−H Acidity of the Distal Base

Abstract

The distal hydrogen bond (H-bond) in dioxygen-binding proteins is crucial for the discrimination of O2 with respect to CO or NO. We report the preparation and characterization of a series of Zn(II) porphyrins, with one of three meso-phenyl rings bearing both an alkyl-tethered proximal imidazole ligand and a heterocyclic distal H-bond donor connected by a rigid acetylene spacer. Previously, we had validated the corresponding Co(II) complexes as synthetic model systems for dioxygen-binding heme proteins and demonstrated the structural requirements for proper distal H-bonding to Co(II) -bound dioxygen. Here, we systematically vary the H-bond donor ability of the distal heterocycles, as predicted based on pKa values. The H-bond in the dioxygen adducts of the Co(II) porphyrins was directly measured by Q-band Davies-ENDOR spectroscopy. It was shown that the strength of the hyperfine coupling between the dioxygen radical and the distal H-atom increases with enhanced acidity of the H-bond donor.

Design and Synthesis of New Triazole‐Benzimidazole Derivatives as Potential PRMT5 Inhibitors

“…4‐Iodo‐2‐nitroaniline ( 2 ) was obtained in better yield through iodination of 2‐nitro aniline 1 employing HFIP (Hexafluoroisopropanol) and NIS [25] . This upon reduction by SnCl 2 .2H 2 O in ethanol‐HCl yields diamine 3 [26] . Sonogashira coupling of diamine 3 with TMS‐acetylene (Trimethylsilylacetylene) catalysed by CuI and Pd(PPh 3 ) 4 [Tetrakis(triphenylphosphine)‐palladium (0)] furnished 4‐((trimethylsilyl)ethynyl) benzene‐1,2‐diamine ( 4 ) [27] .…”

“…[25] This upon reduction by SnCl 2 .2H 2 O in ethanol-HCl yields diamine 3. [26] Sonogashira coupling of diamine 3 with TMS-acetylene (Trimethylsilylacetylene) catalysed by CuI and Pd(PPh 3 ) 4 [Tetrakis(triphenylphosphine)-palladium (0)] furnished 4-((trimethylsilyl)ethynyl) benzene-1,2-diamine (4). [27] The synthesis of 2-amino benzimidazole (5) employing cyanogen bromide as a facile cyclization partner.…”

EUCheMS‐Vorlesung: G. Férey und C. Moberg / August‐Wilhelm‐von‐Hofmann‐ Denkmünze: B. L. Feringa / Catalán‐Sabatier‐Preis: J.‐M. Tarascon / Elhuyar‐Goldschmidt‐Vorlesung: N. Martín und F. Würthner / Preise der European Federation for Medicinal Chemistry: F. Diederich und P. J. Hergenrother / Eni‐Preise: J. A. Lercher und D. Milstein

“…Diederich war 1994–2013 Mitglied des Kuratoriums der Angewandten Chemie (darunter zehn Jahre dessen Vorsitzender) und ist derzeit Mitglied in Boards der Angewandten Chemie , von Chemistry—An Asian Journal , Chemistry—A European Journal , ChemistrySelect und ChemMedChem . Vor kurzem hat er in Chemistry—A European Journal über die H‐Brücken‐Stärke in Hämproteinmodellen berichtet . Diederich wurde 2015 ChemPubSoc Europe Fellow, und er wurde kürzlich auch in die Academia Scientiarum et Artium Europaea gewählt.…”

EUCheMS Lecture Award: G. Férey and C. Moberg / August Wilhelm von Hofmann Memorial Medal: B. L. Feringa / Catalán–Sabatier Prize: J.‐M. Tarascon / Elhuyar–Goldschmidt Lectureship: N. Martín and F. Würthner / European Federation for Medicinal Chemistry Awards: F. Diederich and P. J. Hergenrother / Eni Awards: J. A. Lercher and D. Milstein

“…Diederich was a member of the Editorial Board of Angewandte Chemie from 1994–2013 (including ten years as Chairman), and is currently on the editorial or advisory boards of Angewandte Chemie , Chemistry—An Asian Journal , Chemistry—A European Journal , ChemistrySelect , and ChemMedChem . He has recently reported in Chemistry—A European Journal on the hydrogen‐bond strength in heme protein models . Diederich was elected a ChemPubSoc Europe Fellow in 2015, and was also recently elected to the European Academy of Sciences and Arts.…”