PMID- 34555598 OWN - NLM STAT- MEDLINE DCOM- 20220222 LR - 20220222 IS - 1873-3344 (Electronic) IS - 0162-0134 (Linking) VI - 225 DP - 2021 Dec TI - Protonation of the oxo-bridged heme/copper assemblies: Modeling the oxidized state of the cytochrome c oxidase active site. PG - 111593 LID - S0162-0134(21)00240-3 [pii] LID - 10.1016/j.jinorgbio.2021.111593 [doi] AB - In this study on model compounds for the resting oxidized state of the iron‑copper binuclear center in cytochrome c oxidase (CcO), we describe the synthesis of a new mu-oxo-heme/Cu complex, [(TPP)Fe(III)-O-Cu(II)(tmpa)][B(C(6)F(5))(4)] (2) TPP: tetraphenyl porphyrinate(2-); TMPA: tris(2-pyridylmethylamine), as well as two protonation events for three mu-oxo-heme/Cu complexes with varying peripheral substituents on the heme site. The addition of increasing amounts of strong acid to these mu-oxo-heme/Cu systems successively led to the generation of the corresponding mu-hydroxo, mu-aquo, and the dissociated complexes. The heme/Cu assemblies bridged through a water ligand are reported here for the first time and the (1)H NMR and (19)F NMR spectral properties are consistent with antiferromagnetically coupled high-spin iron(III) and copper(II) centers. By titration using a series of protonated amines, the pK(a) values for the corresponding mu-hydroxo-heme/Cu species (i.e., the first protonation event) have been reported and compared with the pK(a) ranges previously estimated for related systems. These synthetic systems may represent structural models for the oxidized Fe(III)-X-Cu(II) resting state, or turnover intermediates and can be employed to clarify the nature of proton/electron transfer events in CcO. SYNOPSIS: The resting oxidized state of the cytochrome c oxidase active site contains an Fe(a3)-OH(x)-Cu(B) moiety. Here, we investigated two successive protonation events, for a series of mu-oxo-heme/Cu assemblies and reported the pK(a) values for the first protonation event. The mu-aquo-heme/Cu complexes described here are the first examples of such systems. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Carrasco, Maria C AU - Carrasco MC AD - Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA. FAU - Dezarn, Katherine J AU - Dezarn KJ AD - Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA. FAU - Khan, Firoz Shah Tuglak AU - Khan FST AD - Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA. FAU - Hematian, Shabnam AU - Hematian S AD - Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA. Electronic address: s_hemati@uncg.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210827 PL - United States TA - J Inorg Biochem JT - Journal of inorganic biochemistry JID - 7905788 RN - 0 (Amines) RN - 0 (Coordination Complexes) RN - 0 (Protons) RN - 42VZT0U6YR (Heme) RN - 789U1901C5 (Copper) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Amines/chemistry MH - Catalytic Domain MH - Coordination Complexes/chemical synthesis/*chemistry MH - Copper/chemistry MH - Electron Transport Complex IV/chemistry MH - Heme/*analogs & derivatives MH - Models, Chemical MH - Molecular Structure MH - Protons MH - Titrimetry OTO - NOTNLM OT - Acid dissociation constant OT - Antiferromagnetic coupling OT - Bridging ligand OT - Cytochrome c oxidase OT - Paramagnetic NMR OT - Protonation EDAT- 2021/09/24 06:00 MHDA- 2022/02/23 06:00 CRDT- 2021/09/23 20:19 PHST- 2021/06/30 00:00 [received] PHST- 2021/08/20 00:00 [revised] PHST- 2021/08/22 00:00 [accepted] PHST- 2021/09/24 06:00 [pubmed] PHST- 2022/02/23 06:00 [medline] PHST- 2021/09/23 20:19 [entrez] AID - S0162-0134(21)00240-3 [pii] AID - 10.1016/j.jinorgbio.2021.111593 [doi] PST - ppublish SO - J Inorg Biochem. 2021 Dec;225:111593. doi: 10.1016/j.jinorgbio.2021.111593. Epub 2021 Aug 27.