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Abstract

Cytochrome c oxidase (CcO) is the enzyme that makes aerobic metabolism possible by catalyzing the final step in the respiratory electron-transfer chain-a four-electron (4 e), four-proton (4 H þ ) reduction of O 2 to water. [1, 2] Catalysis proceeds at the heterobimetallic heme/Cu B site ( Figure 1). [3] The Fe center is the site of O 2 binding, and reduction of O 2 is coupled to oxidation of Cu I B , at least under single-turnover conditions. [4, 5] One of the poorly understood questions regarding the structure±activity relationship at the heme/ Cu B site is how the heme reactivity is affected by the closely positioned, positively charged Cu B center. Such effects are expected to manifest themselves in an attenuated affinity of the Fe center for small molecules. Among these, CO and the ions CN À and N 3 À , are of particular interest, because the cytotoxicity of the CN À and N 3 À ions arises from the inhibition of CcO and resultant respiratory shutdown, [7] and CO is an endogenous inhibitor of ferrohemes. The mode of CN À ion binding to the heme/Cu B site and the effect(s) of Cu B on such binding remain controversial. [8] Likewise, contradictory results have been reported for differences in the CO affinities of the wild-type and Cu B -free mutants of terminal oxidases. [9,10] Previously, we demonstrated that the biomimetic complexes shown in Figure 1 b quantitatively reproduce the key reactivity of the heme/Cu B site [6,11] and thus allow the study of questions that are not easily addressed by working with the enzyme itself. Herein we report that the steady-state reduc-ZUSCHRIFTEN

Inhibition of Electrocatalytic O2 Reduction of Functional CcO Models by Competitive, Non-Competitive, and Mixed Inhibitors

“…it takes 4–5 times more CN − to inhibit FeCu catalyst than the Fe-only catalyst. Previously it was invoked that this possibly reflects a difference in CN − binding to the fully reduced catalyst 33. Indeed the ligand binding studies reflect a weakening of CN − binding to the FeCu complex by a factor of 4.5 consistent with the inhibition data.…”

“…KPF 6 , Sodium Azide, Sodium Cyanide, Cabon Monoxide, Sodium Nitrite were commercial grade and used without further purification. The concentration of CN − in a pH 7 buffer was corrected for its loss as HCN using the Henderson equation 33. The CO solutions were made by adding calculated aliquots of saturated CO in de-ionized water in air saturated buffer solutions.…”

On the Nature of Actinide– and Lanthanide–Metal Bonds in Heterobimetallic Compounds

“…Chemists have pursued the challenge of synthesizing a wide variety of metal-metal bonds for the past fifty years with motivations ranging from fundamental interest [1][2][3][4] to more practical applications for example, molecular wires [5] and small molecule activation. [6] Researchers have asked why stable metal-metal bonding interactions form, what is their reactivity, and what potential uses in catalysis, metal surface chemistry, or bioinorganic reactivity may be possible.…”

“…[7] While challenging, many attempts to isolate complexes containing main group homodinuclear metal-metal bonds have proven successful and as a result this type of bonding is now generally well understood. [1] In contrast, transition metal heterobimetallic metal-metal bonds are less prevalent since they present more synthetic challenges; however, the highly ionic bonds in such compounds provide opportunities for very different chemistry than are found for their homobimetallic counterparts. Heterobimetallic bonds have inequivalent metal centers.…”

Σχεδιασμός σύνθεση και φυσικοχημικός χαρακτηρισμός ενώσεων - μοντέλων κυτοχρωμικής c οξειδάσης

“…Το ιόν του κυανίου (CN -) καθώς και το µονοξείδιο του άνθρακα (CO) είναι γνωστό ότι αποτελούν ανταγωνιστές του οξυγόνου και η δέσµευσή τους στην κυτοχρωµική c οξειδάση έχει ως αποτέλεσµα την αναστολή της λειτουργίας του ενζύµου. Στα βιοµιµητικά µοντέλα 33-35 µελετήθηκε η επίδραση του ιόντος του χαλκού ως προς την αναστολή της καταλυτικής τους ικανότητας παρουσία των ιόντων κυανίου καθώς και του µονοξειδίου του άνθρακα 72. Ελήφθησαν τα βολταµογραφήµατα των συνθετικών αναλόγων όταν διαθέτουν και όταν απουσιάζει ο χαλκός έχοντας προσθέσει στο διάλυµα είτε ιόντα CNείτε CO. Τα µοντέλα όταν περιέχουν το ιόν του χαλκού εµφανίζουν µεγαλύτερη ανθεκτικότητα ως προς την αναστολή από τα συγκεκριµένα ιόντα.…”