The mechanisms of heterolytic versus homolytic O−O bond cleavage of H2O2, tert-butyl hydroperoxide (t-BuOOH), 2-methyl-1-phenyl-2-propyl hydroperoxide (MPPH), and m-chloroperoxybenzoic acid (m-CPBA) by iron(III) porphyrin complexes have been studied by carrying out catalytic epoxidations of cyclohexene in protic solvent. In these reactions, various iron(III) porphyrin complexes containing electron-withdrawing and -donating substituents on phenyl groups at the meso position of the porphyrin ring were employed to study the electronic effect of porphyrin ligands on the heterolytic versus homolytic O−O bond cleavage of the hydroperoxides. In addition, various imidazoles were introduced as axial ligands to investigate the electronic effect of axial ligands on the pathways of hydroperoxide O−O bond cleavage. Unlike the previous suggestions by Traylor, Bruice, and co-workers, the hydroperoxide O−O bonds were found to be cleaved both heterolytically and homolytically and partitioning between heterolysis and homolysis was significantly affected by the electronic nature of the iron porphyrin complexes (i.e., electronic properties of porphyrin and axial ligands). Electron-deficient iron porphyrin complexes show a tendency to cleave the hydroperoxide O−O bonds heterolytically, whereas electron-rich iron porphyrin complexes cleave the hydroperoxide O−O bonds homolytically. The heterolytic versus homolytic O−O bond cleavage of the hydroperoxides was also found to be significantly affected by the substituent of the hydroperoxides, ROOH (R = C(O)R‘, H, C(CH3)3, and C(CH3)2CH2Ph for m-CPBA, H2O2, t-BuOOH, and MPPH, respectively), in which the tendency of O−O bond heterolysis was in the order of m-CPBA > H2O2 > t-BuOOH > MPPH. This result indicates that the O−O bond of hydroperoxides containing electron-donating tert-alkyl groups such as t-BuOOH and MPPH tends to be cleaved homolytically, whereas electron-withdrawing substituents such as an acyl group in m-CPBA facilitates O−O bond heterolysis. Since we have observed that the homolytic O−O bond cleavage of hydroperoxides prevails in the reactions performed with electron-rich iron porphyrin complexes and with hydroperoxides containing electron-donating substituents such as the tert-alkyl group, we suggest that the homolytic O−O bond cleavage is facilitated when more electron density resides on the O−O bond of (Porp)Fe(III)-OOR intermediates. We also present convincing evidence that the previous assertion that the reactions of iron(III) porphyrin complexes with hydrogen peroxide and tert-alkyl hydroperoxides invariably proceed by heterolytic O−O bond cleavage in protic solvent and that the failure to obtain high epoxide yields in iron porphyrin complex-catalyzed epoxidation of olefins by hydroperoxides is due to the mechanism of heterolytic O−O bond cleavage followed by a fast hydroperoxide oxidation is highly unlike.

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Abstract. Aerosol hygroscopicity strongly influences the number size distribution, phase state, optical properties, and multiphase chemistry of aerosol particles. Due to the large number of organic species in atmospheric aerosols, the determination of the hygroscopicity of ambient aerosols remains challenging. In this study, we measured the hygroscopic properties of 23 organics, including carboxylic acids, amino acids, sugars, and alcohols, using a hygroscopicity tandem differential mobility analyzer (HTDMA). Earlier studies have characterized the hygroscopicity either for a limited number of organic compounds using similar techniques or for particles at sizes beyond the microscale range or even bulk samples using other methodologies. Here, we validate these studies and extend the data by measuring the hygroscopicity of a broader suite of organics for particles with sizes under the submicrometer range that are more atmospherically relevant. Moreover, we systematically evaluate the roles of that related physicochemical properties play in organic hygroscopicity. We show that the hygroscopicity of organics varies widely with functional groups and organics with the same carbon number but that more functional groups show higher hygroscopicity. However, some isomers that are very similar in molecular structure show quite different hygroscopicity, demonstrating that other physicochemical properties, such as water solubility, may contribute to their hygroscopicity as well. If the organics are fully dissolved in water (solubility >7×10-1 g mL−1), we found that their hygroscopicity is mainly controlled by their molecular weight. For the organics that are not fully dissolved in water (slightly soluble: 5×10-4 g mL−1 < solubility < 7×10-1 g mL−1), we observed that some of them show no obvious water uptake, which is probably due to the fact that they may not deliquesce under our studied conditions up to 90 % relative humidity (RH). The other type of slightly soluble organic material is moderately hygroscopic, and the larger its solubility is, the higher its hygroscopicity will be. Moreover, the hygroscopicity of organics generally increased with O:C ratios, although this relationship is not linear.

The effects of the linker arm rigidity and size on melanocortin receptor selectivity were explored in a series of compounds using cyclic lactam a-melanocyte-stimulating hormone template. A variety of dicarboxylic acid linkers introduced between the a-amino group of His 6 and the e-amino group of Lys 10 lead to high-affinity, selective human melanocortin receptor-1 and -5 (hMC1R and hMC5R) antagonists. The incorporation of hydrophilic functions into the linker arm was found to be unfavorable for both binding potency and receptor selectivity. Analogs 8 and 9 containing highly conformationally constrained hydrophobic linkers (m-and p-phthalic acids) were found to be selective nanomolar range hMC1R antagonists (IC 50 ¼ 7 and 4 nM, respectively), whereas the employment of a small conformationally constrained linker (maleic acid) resulted in a high-affinity (IC 50 ¼ 19 nM) and selective hMC5R antagonist (analog 12). These newly developed melanotropins will serve as critical biochemical tools for elucidating the full spectrum of functions performed by the physiologically important melanocortin-1 and -5 receptors.Key words: a-melanocyte-stimulating hormone, antagonist, human melanocortin-1 receptor, human melanocortin-5 receptor, macrocyclic, melanocortin, peptide Abbreviations: Abbreviations used for amino acids and designation of peptides follow the rules of the IUPAC-IUB Commission of Biochemical Nomenclature in J. Biol. Chem. 1972, 247, 977-983. The following additional abbreviations are used: All, allyl; Alloc, allyloxycarbonyl; Boc, tert-butyloxycarbonyl; Fmoc, fluorenylmethoxycarbonyl; CH 3 CN, acetonitrile; DCM, dichloromethane; DIPEA, diisopropylethylamine; DMF, N,N-dimethylformamide; DIC, diisopropyl carbodiimide; HBTU, 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; HOBt, N-hydroxybenzotriazole; hMCR, human melanocortin receptor; MSH, melanocytestimulating hormone; Nal(2¢), 2¢-naphthylalanine; Pbf, 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl; PyBOP, benzotriazol-1-yloxy-tris-pyrrolidinophosphonium hexafluorophosphate; TFA, trifluoroacetic acid; Trt, trityl; SPPS, solid-phase peptide synthesis; RP-HPLC, reverse-phase highperformance liquid chromatography; hMC1R, human melanocortin-1 receptor; a-MSH, Ac-SerTyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH 2 ; NDP-a-MSH, Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-ArgTrp-Gly-Lys-Pro-Val-NH 2 . Received 6 April 2006, revised 25 April 2006 and accepted for publication 26 April 2006The natural melanocortin agonists, a-, b-, c-melanocyte-stimulating hormones (MSHs), and adrenocorticotropin have been receiving great attention in the recent years because of their involvement in a large number of multifaceted biological actions, including skin pigmentation (1-3), control of the immune system (1-4), erectile function (5-9), blood pressure and heart rate (10), control of feeding behavior and energy homeostasis (11-17), modulation of aggressive/defensive behavior (18), and mediation of pain (19). These endogenous neuropeptides are ligands for the fiv...

The structural stability of nanoalloys is a challenging research subject due to the complexity of size, shape, composition, and chemical ordering. The genetic algorithm is a popular global optimization method that can efficiently search for the ground-state nanoalloy structure. However, the algorithm suffers from three significant limitations: the efficiency and accuracy of the energy evaluator and the algorithm’s efficiency. Here we describe the construction of a neural network potential intended for rapid and accurate energy predictions of Pt-Ni nanoalloys of various sizes, shapes, and compositions. We further introduce a symmetry-constrained genetic algorithm that significantly improves the efficiency and viability of the algorithm for realistic size nanoalloys. The combination of the two allows us to explore the space of homotops and compositions of Pt-Ni nanoalloys consisting of up to 4033 atoms and quantitatively report the interplay of shape, size, and composition on the dominant chemical ordering patterns.

Obesity and obesity-associated diseases are linked to dysregulation of the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. Identification of the factors that regulate PPARγ expression and activity is crucial for combating obesity. However, the ubiquitin E3 ligases that target PPARγ for proteasomal degradation have been rarely identified, and their functions in vivo have not been characterized. Here we report that CUL4B-RING E3 ligase (CRL4B) negatively regulates PPARγ by promoting its polyubiquitination and proteasomal degradation. Depletion of CUL4B led to upregulation of PPARγ-regulated genes and facilitated adipogenesis. Adipocyte-specific Cul4b knockout (AKO) mice being fed a high-fat diet exhibited increased body fat accumulation that was mediated by increased adipogenesis. However, AKO mice showed improved metabolic phenotypes, including increased insulin sensitivity and glucose tolerance. Correspondingly, there was a decreased inflammatory response in adipose tissues of AKO mice. Genetic inhibition of CUL4B thus appears to phenocopy the beneficial effects of PPARγ agonists. Collectively, this study establishes a critical role of CRL4B in the regulation of PPARγ stability and insulin sensitivity and suggests that CUL4B could be a potential therapeutic target for combating obesity and metabolic syndromes.

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As a quantum material, Weyl semimetal has a series of electronic-band-structure features, including Weyl points with left and right chirality and corresponding Berry curvature, which have been observed in experiments. These band-structure features also lead to some unique nonlinear properties, especially high-order harmonic generation (HHG) due to the dynamic process of electrons under strong laser excitation, which has remained unexplored previously. Herein, we obtain effective HHG in type-II Weyl semimetal β-WP2 crystals, where both odd and even orders are observed, with spectra extending into the vacuum ultraviolet region (190 nm, 10th order), even under fairly low femtosecond laser intensity. In-depth studies have interpreted that odd-order harmonics come from the Bloch electron oscillation, while even orders are attributed to Bloch oscillations under the “spike-like” Berry curvature at Weyl points. With crystallographic orientation-dependent HHG spectra, we further quantitatively retrieved the electronic band structure and Berry curvature of β-WP2. These findings may open the door for exploiting metallic/semimetallic states as solid platforms for deep ultraviolet radiation and offer an all-optical and pragmatic solution to characterize the complicated multiband electronic structure and Berry curvature of quantum topological materials.