Redox-inactive metal ions play vital roles in biological O2 activation and oxidation reactions of various substrates. Recently, we showed a distinct reactivity of a peroxocobalt­(III) complex bearing a tetradentate macrocyclic ligand, [CoIII(TBDAP)­(O2)]+ (1) (TBDAP = N,N′-di-tert-butyl-2,11-diaza­[3.3]­(2,6)­pyridinophane), toward nitriles that afforded a series of hydroximato­cobalt­(III) complexes, [CoIII(TBDAP)­(R–C­(NO)­O)]+ (R = Me (3), Et, and Ph). In this study, we report the effects of redox-inactive metal ions on nitrile activation of 1. In the presence of redox-inactive metal ions such as Zn2+, La3+, Lu3+, and Y3+, the reaction does not form the hydroximato­cobalt­(III) complex but instead gives peroxyimidato­cobalt­(III) complexes, [CoIII(TBDAP)­(R–C­(NH)­O2)]2+ (R = Me (2) and Ph (2 Ph )). These new intermediates were characterized by various physicochemical methods including X-ray diffraction analysis. The rates of the formation of 2 are found to correlate with the Lewis acidity of the additive metal ions. Moreover, complex 2 was readily converted to 3 by the addition of a base. In the presence of Al3+, Sc3+, or H+, 1 is converted to [CoIII(TBDAP)­(O2H)­(MeCN)]2+ (4), and further reaction with nitriles did not occur. These results reveal that the reactivity of the peroxocobalt­(III) complex 1 in nitrile activation can be regulated by the redox-inactive metal ions and their Lewis acidity. DFT calculations show that the redox-inactive metal ions stabilize the peroxo character of end-on Co−η1-O2 intermediate through the charge reorganization from a CoII–superoxo to a CoIII–peroxo intermediate. A complete mechanistic model explaining the role of the Lewis acid is presented.

High-valent transition metal–hydroxide complexes have been proposed as essential intermediates in biological and synthetic catalytic reactions. In this work, we report the single-crystal X-ray structure and spectroscopic characteristics of a mononuclear nonporphyrinic MnIV–(OH) complex, [MnIV(Me3-TPADP)­(OH)­(OCH2CH3)]2+ (2), using various physicochemical methods. Likewise, [MnIV(Me3-TPADP)­(OH)­(OCH2CF3)]2+ (3), which is thermally stable at room temperature, was also synthesized and characterized spectroscopically. The MnIV–(OH) adducts are capable of performing oxidation reactions with external organic substrates such as C–H bond activation, sulfoxidation, and epoxidation. Kinetic studies, involving the Hammett correlation and kinetic isotope effect, and product analyses indicate that 2 and 3 exhibit electrophilic oxidative reactivity toward hydrocarbons. Density functional theory calculations support the assigned electronic structure and show that direct C–H bond activation of the MnIV–(OH) species is indeed possible.

A series of cobalt(III)–peroxo complexes, [CoIII(R2-TBDAP)(O2)]+ (1 R2 ; R2 = Cl, H, and OMe), and cobalt(III)–hydroperoxo complexes, [CoIII(R2-TBDAP)(O2H)(CH3CN)]2+ (2 R2 ), bearing electronically tuned tetraazamacrocyclic ligands (R2-TBDAP = N,N′-di-tert-butyl-2,11-diaza[3.3](2,6)-p-R2-pyridinophane) were prepared from their cobalt(II) precursors and characterized by various physicochemical methods. The X-ray diffraction and spectroscopic analyses unambiguously showed that all 1 R2 compounds have similar octahedral geometry with a side-on peroxocobalt(III) moiety, but the O–O bond lengths of 1 Cl [1.398(3) Å] and 1 OMe [1.401(4) Å] were shorter than that of 1 H [1.456(3) Å] due to the different spin states. For 2 R2 , the O–O bond vibration energies of 2 Cl and 2 OMe were identical at 853 cm–1 (856 cm–1 for 2 H ), but their Co–O bond vibration frequencies were observed at 572 cm–1 for 2 Cl and 550 cm–1 for 2 OMe , respectively, by resonance Raman spectroscopy (560 cm–1 for 2 H ). Interestingly, the redox potentials (E 1/2) of 2 R2 increased in the order of 2 OMe (0.19 V) < 2 H (0.24 V) < 2 Cl (0.34 V) according to the electron richness of the R2-TBDAP ligands, but the oxygen-atom-transfer reactivities of 2 R2 showed a reverse trend (k 2: 2 Cl < 2 H < 2 OMe ) with a 13-fold rate enhancement at 2 OMe over 2 Cl in a sulfoxidation reaction with thioanisole. Although the reactivity trend contradicts the general consideration that electron-rich metal–oxygen species with low E 1/2 values have sluggish electrophilic reactivity, this could be explained by a weak Co–O bond vibration of 2 OMe in the unusual reaction pathway. These results provide considerable insight into the electronic nature–reactivity relationship of metal–oxygen species.

Alzheimer’s disease (AD) is the most common form of dementia that affects millions of people worldwide. The hallmark of this disease is the accumulation of amyloid-beta (Abeta) aggregates that lead to neuronal death and cognitive defects. Various chemical reagents, including transition metal complexes, have been developed to change Abeta peptides with the consequent impact on their aggregation profiles; however, the examples of Abeta modifications by transition metal complexes are very limited. Here we report, for the first time, the site-specific modifications of Abeta peptides using a mononuclear cobalt complex, [CoII(TBDAP)(H2O)(NO3)](NO3) (Co(II)(TBDAP); TBDAP = N,N-di-tert-butyl-2,11-diaza[3.3](2,6)-pyridinophane). Co(II)(TBDAP) can induce modifications onto Abeta peptides, including decarboxylation and deamination, fragmentation, and a combination of both. Our spectrometric and spectroscopic studies manifest that the oxidation of the Co(II) center to Co(III) by O2 is a crucial step for inducing these modifications, which is further supported based on the reactivities of a newly synthesized Co(III) complex, [CoIII(TBDAP)(Cl)2](NO3) (Co(III)(TBDAP)), towards Abeta peptides. Such modifications onto Abeta by Co(II)(TBDAP) can redirect its on-pathway aggregation to off-pathway, yielding relatively less toxic short fibrils or amorphous aggregates. Our work provides valuable insights into the distinct reactivities of cobalt complexes towards Abeta peptides, which offers a novel strategy to control Abeta amyloidogenesis using transition metal complexes.

Alzheimer’s disease (AD) is the most common form of dementia that affects millions of people worldwide. The hallmark of this disease is the accumulation of amyloid-beta (Abeta) aggregates that lead to neuronal death and cognitive defects. Various chemical reagents, including transition metal complexes, have been developed to change Abeta peptides with the consequent impact on their aggregation profiles; however, the examples of Abeta modifications by transition metal complexes are very limited. Here we report, for the first time, the site-specific modifications of Abeta peptides using a mononuclear cobalt complex, [CoII(TBDAP)(H2O)(NO3)](NO3) (Co(II)(TBDAP); TBDAP = N,N-di-tert-butyl-2,11-diaza[3.3](2,6)-pyridinophane). Co(II)(TBDAP) can induce modifications onto Abeta peptides, including decarboxylation and deamination, fragmentation, and a combination of both. Our spectrometric and spectroscopic studies manifest that the oxidation of the Co(II) center to Co(III) by O2 is a crucial step for inducing these modifications, which is further supported based on the reactivities of a newly synthesized Co(III) complex, [CoIII(TBDAP)(Cl)2](NO3) (Co(III)(TBDAP)), towards Abeta peptides. Such modifications onto Abeta by Co(II)(TBDAP) can redirect its on-pathway aggregation to off-pathway, yielding relatively less toxic short fibrils or amorphous aggregates. Our work provides valuable insights into the distinct reactivities of cobalt complexes towards Abeta peptides, which offers a novel strategy to control Abeta amyloidogenesis using transition metal complexes.