Hydrogen Bond-Enabled Heterolytic and Homolytic Peroxide Activation within Nonheme Copper(II)-Alkylperoxo Complexes

To explore the reactivity of copper-alkylperoxo species enabled by the heterolytic peroxide activation, room-temperature stable mononuclear nonheme copper­(II)–alkylperoxo complexes bearing a N-(2-ethoxyethanol)-bis(2-picolyl)­amine ligand (HN3O2), [CuII(OOR)­(HN3O2)]+ (R = cumyl or tBu), were synthesized and spectroscopically characterized. A combined experimental and computational investigation on the reactivity and reaction mechanisms in the phosphorus oxidation, C–H bond activation, and aldehyde deformylation reactions by the copper­(II)–alkylperoxo complexes has been conducted. DFT-optimized structures suggested that a hydrogen bonding interaction exists between the ethoxyethanol backbone of the HN3O2 ligand and either the proximal or distal oxygen atom of the alkylperoxide moiety, and this interaction consequently results in the enhanced stability of the copper­(II)–alkylperoxo species. In the phosphorus oxidation reaction, both experimental and computational results indicated that a phosphine-triggered heterolytic O–O bond cleavage occurred to yield phosphine oxide and alcohol products. DFT calculations suggested that (i) the H-bonding between the ethoxyethanol backbone and distal oxygen of the alkylperoxide moiety and (ii) the phosphine binding to the proximal oxygen of the alkylperoxide moiety engendered the heterolytic peroxide activation. In the C–H bond activation reactions, temperature-dependent reactivity of the copper­(II)–alkylperoxo complexes was observed, and a relatively strong activation energy of 95 kcal mol–1 was required to promote the homolytic peroxide activation. A rate-limiting hydrogen atom abstraction reaction of xanthene by the putative copper­(II)-oxyl radical resulted in the formation of the dimeric copper product and the substrate radical that further underwent autocatalytic oxidation reactions to form an oxygen incorporated product. Finally, amphoteric reactivity of copper­(II)–alkylperoxo complexes has been assessed by conducting kinetic studies and product analysis of the aldehyde deformylation reaction

Acremostrictin, a Highly Oxygenated Metabolite from the Marine Fungus <i>Acremonium strictum</i>

The novel natural product acremostrictin (1) was isolated from the culture broth of Acremonium strictum, a marine fungus collected from a Choristida sponge off the coast of Korea. Structurally, acremostrictin is a tricyclic lactone of an unprecedented skeletal class based on combined spectroscopic and X-ray crystallographic analyses. The new compound exhibited weak antibacterial and moderate antioxidant activities

DataSheet_1_Epigallocatechin-3-Gallate as a Novel Vaccine Adjuvant.docx

Vaccine adjuvants from natural resources have been utilized for enhancing vaccine efficacy against infectious diseases. This study examined the potential use of catechins, polyphenolic materials derived from green tea, as adjuvants for subunit and inactivated vaccines. Previously, catechins have been documented to have irreversible virucidal function, with the possible applicability in the inactivated viral vaccine platform. In a mouse model, the coadministration of epigallocatechin-3-gallate (EGCG) with influenza hemagglutinin (HA) antigens induced high levels of neutralizing antibodies, comparable to that induced by alum, providing complete protection against the lethal challenge. Adjuvant effects were observed for all types of HA antigens, including recombinant full-length HA and HA1 globular domain, and egg-derived inactivated split influenza vaccines. The combination of alum and EGCG further increased neutralizing (NT) antibody titers with the corresponding hemagglutination inhibition (HI) titers, demonstrating a dose-sparing effect. Remarkably, EGCG induced immunoglobulin isotype switching from IgG1 to IgG2a (approximately >64–700 fold increase), exerting a more balanced TH1/TH2 response compared to alum. The upregulation of IgG2a correlated with significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) function (approximately 14 fold increase), providing a potent effector-mediated protection in addition to NT and HI. As the first report on a novel class of vaccine adjuvants with built-in virucidal activities, the results of this study will help improve the efficacy and safety of vaccines for pandemic preparedness.</p