Intramolecular Hydrogen Bonding Enhances Stability and Reactivity of Mononuclear Cupric Superoxide Complexes

Abstract

[(L)Cu(O)] (i.e., cupric-superoxo) complexes, as the first and/or key reactive intermediates in (bio)chemical Cu-oxidative processes, including in the monooxygenases PHM and DβM, have been systematically stabilized by intramolecular hydrogen bonding within a TMPA ligand-based framework. Also, gradual strengthening of ligand-derived H-bonding dramatically enhances the [(L)Cu(O)] reactivity toward hydrogen-atom abstraction (HAA) of phenolic O-H bonds. Spectroscopic properties of the superoxo complexes and their azido analogues, [(L)Cu(N)], also systematically change as a function of ligand H-bonding capability.

Impact of Intramolecular Hydrogen Bonding on the Reactivity of Cupric Superoxide Complexes with O−H and C−H Substrates

“…These species exhibit the highly characteristic UV/Vis signatures observed for other end-on-bound (Cu II À O À OC À ) cupric superoxides [11] and are stable at À135 8 8C( no selfdecomposition for over 3h). Interestingly,t he l max value of the high-energy feature is sequentially blue-shifted [23] upon addition of H-bonding groups (Table S1 and Figure S1 in the Supporting Information);asimilar trend has been previously observed with azido [(L)Cu II (N 3…”

“…[11] Thus,t he study of synthetic cupric superoxide model complexes to further understand their structures, physical-spectroscopic properties,a nd correlated reactivity toward the hydroxylation of substrates containing strong CÀ Hb onds is of considerable interest in catalysis.Ty pically,t hese primary copper-dioxygen superoxide model species [11,15,16] are difficult to study due to their tendency to form secondary Cu 2 -O 2 adducts (that is, m-1,2peroxo-dicopper(II), side-on peroxodicopper(II), or bis-moxodicopper(III) complexes) in solution. Researchers have been able to prevent the formation of 2:1C u:O 2 adducts through ligand design;the addition of as econdary coordination sphere of sterically bulky groups [17][18][19][20][21] or hydrogenbonding (H-bonding) moieties [22,23] allows for the stabilization of cupric superoxide complexes.T hese H-bonding effects, noted for superoxide and peroxide stabilization via amide and amine H-bonds, [24,25] play ar ole similar to that of the acidic (thus H-bonding) O 2 -binding pocket in the single coppercontaining formylglycine-generating enzyme (FGE). [26] However,t here have been limited reports on how such factors influence the electrophilic reactivity of cupric superoxide complexes toward OÀHo rC ÀHs ubstrates, [11,15,22,23,27] particularly those of biological interest.…”

“…[28,29] TheH-bonding moieties examined are one or two amino (ÀNH 2 )o rp ivalamido (ÀHNC(O)C(CH 3 ) 3 ,P V) groups;methyl ( À CH 3 )substituents are used as steric controls since they are similar in size to the amino groups.T wo aspects are considered:1)the relative stabilities between the primary and secondary (di)copper-dioxygen adducts formed from the reaction of copper(I) and O 2 ,a nd 2) the electrophilic reactivity of cupric superoxide complexes with substrates containing weak-to-moderate O À Ha nd C À HB DEs.O ur findings include that increasing the strength and/or number of the H-bonding groups enhances both aspects,w ith the most reactive cupric superoxide utilizing ðPVÞ 2 TMPA; the reactivity with respect to the OÀHBDE of the substrate is increased by more than 10 kcal mol À1 compared to that for [(TMPA)Cu II -(O 2 C À )] + .I ti ss hown that this species,[ ( ðPVÞ 2 TMPA)Cu II -(O 2 C À )] + ,can react with substrates containing O À HB DEs up to 91.5 kcal mol À1 (p-methylphenol) and C À HB DEs up to 79.7 kcal mol À1 (dihydroanthracene);this makes the complex one of the most reactive synthetic cupric superoxides reported to date. [21,30] Spectroscopic investigation of the new (or previously examined) [22,23] ðX 1 ÞðX 2 Þ TMPA-Cu I /O 2 adducts at À135 8 8Ci n MeTHF [31] reveals that while complexes bearing ligands without H-bonding moieties (that is,X 1 and/or X 2 = À CH 3 ) form traditionally secondary Cu 2 O 2 -derived products; [32] new LCu I /O 2 chemistry is observed for the complexes incorporating one or two amino-or pivalamido-containing ligands (see below).…”

Polypyridyl‐Based Copper Phenanthrene Complexes: A New Type of Stabilized Artificial Chemical Nuclease

“…Stabilization of the copper complex may also be achieved by coordination to polypyridyl ligands and multidentate complexes e.g., tris(2‐pyridylmethyl)amine, 2,2′,2′′‐tris(dipicolylamino)trimethylamine, and structurally related ligands containing phenoxide or alkoxide bridges, which have received considerable attention as inorganic models of enzyme cofactors. By mimicking the imidazole coordination environment provided by histidine residues in copper proteins, catalytic and structural insights into copper–oxygen activation by monooxygenases or copper‐oxidases have been provided . Arising from these observations, Karlin, Rokita and co‐workers have explored the application of mono‐ and polynuclear polypyridyl scaffolds as new AMNs.…”

“…By mimicking the imidazole coordination environment provided by histidine residues in copper proteins,c atalytic and structural insights into copper-oxygen activation by monooxygenases or copper-oxidases have been provided. [35,36] Arisingf rom theseo bservations, Karlin, Rokita and co-workers have explored the application of mono-and polynuclear polypyridyl scaffolds as new AMNs. Thea ctivation of these nucleasesi sd ependent on the reduction to Cu I , during which, depending on the ligand present,s elective copper-oxo intermediates form and promote the excision of canonical and non-canonicalD NA structures.…”