In the context of a “glyoxylate scenario” of primordial metabolism,1 the reactions of dihydroxyfumarate (DHF) with reactive small molecule aldehydes (e.g., glyoxylate, formaldehyde, glycolaldehyde, and glyceraldehyde) in water were investigated and shown to form dihydroxyacetone, tetrulose, and the two pentuloses, with almost quantitative conversion. The practically clean and selective formation of ketoses in these reactions, with no detectable admixture of aldoses, stands in stark contrast to the formose reaction, where a complex mixture of linear and branched aldoses and ketoses are produced. These results suggest that the reaction of DHF with aldehydes could constitute a reasonable pathway for the formation of carbohydrates and allow for alternative potential prebiotic scenarios to the formose reaction to be considered.

ABSTRACT:Miniemulsions of styrene and butyl acrylate with sodium dodecyl sulfate (SDS) as the surfactant and hexadecane (HDE) and cetyl alcohol (HDL) as cosurfactants were prepared under high-speed stirring or ultrasonification. Results indicate that the stability of miniemulsions produced with HDE is more stable than that with HDL, when the feeding method, in which the cosurfactant is mixed with monomers, is used. There is an optical ratio ( 1 4 ) of the surfactant to the cosurfactant for maximum stabilization of the miniemulsions. The miniemulsions prepared by ultrasonification are much more stable than those by high-speed stirring. Also, a stable miniemulsion can be prepared at lower temperature (45ЊC) when homogenizing way of ultrasonification is used. The emulsions were of a droplet-size range common to miniemulsions and some of them exhibited long-term stabilities (3 months). When these emulsions were initiated, particle formation occurred predominantly by monomer droplet nucleation. The effects of temperature, ultrasonification time, ratio of monomers, and concentrations of surfactant, cosurfactant, and initiator on the polymerization rate, conversion, and particle size were determined. It was found that the miniemulsion copolymerization of styrene and butyl acrylate with a midial amount of a redox initiator ((NH 4 ) 2 S 2 O 8 /NaH SO 3 ) at lower temperature (45ЊC) can be carried out successfully by using a suitable amount of the surfactant SDS (10 m M) and the cosurfactant HDE (40 m M), when a homogenizing way of ultrasonification is applied.

We designed and synthesized a series of novel hybrid histone deacetylase inhibitors based on conjugation of benzamide-type inhibitors with either linear or cyclic peptides. Linear tetrapeptides (compounds 13 and 14), cyclic tetrapeptides (compounds 1 and 11), and heptanediamide-peptide conjugates (compounds 10, 12, 15 and 16) were synthesized through on-resin solid-phase peptide synthesis (SPPS). All compounds were found to be moderate HDAC1 and HDAC3 inhibitors, with IC50 values ranging from 1.3 µM to 532 µM. Interestingly, compound 15 showed 19-fold selectivity for HDAC3 versus HDAC1.Histone deacetylases (HDACs) play important roles in the regulation of gene expression, cell growth, and proliferation, by catalyzing the deacetylation of core histones, tubulin and other proteins. 1 HDAC inhibitors thus have the potential for use in cancer therapy.2 Additionally, recent studies point to the potential therapeutic benefit of HDAC inhibitors in neurodegenerative diseases.3 Eighteen HDACs have been identified in humans and are subdivided into four classes: Class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC84 -7), Class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9 and HDAC108 -11), Class III HDACs (also known as Sirtuins, Sirt 1-7,12 which are NAD + -dependent enzymes) and the lone Class IV HDAC (HDAC1113). Class I, II and IV are Zn ++ -dependent enzymes. 14 Recent studies15 , 16 have demonstrated that HDAC inhibitors can induce growth arrest of tumor cells by inducing terminal differentiation and apoptosis. Numerous different HDAC inhibitors (HDACi) have been reported, including valproic acid (VPA),17 , 18 suberoylanalide hydroxamic acid (SAHA),19 4b,20 and trapoxin21 (Fig. 1). Five classes of HDAC inhibitors can be identified based on their structures: short chain aliphatic carboxylic acids (such as VPA), hydroxamic acids (such as SAHA), benzamides (such as 4b), cyclic peptides (such as Trapoxin B), and the depsipeptides. Most HDAC inhibitors conform to a structural model, where (1) a cap region binds to the enzyme surface, (2) a Zn 2+ coordinating group chelates this bound ion at the bottom of a tubular pocket, and (3) a fiveto seven-atom spacer links the cap region to metal binding group.We recently described a series of benzamide-type, pimelic diphenylamide HDAC inhibitors that show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia20 and Huntington's disease22. In the course of these studies we identified both the enzyme © 2009 Elsevier Ltd. All rights reserved.Correspondence to: Joel M. Gottesfeld. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertai...

Jack of all trades: water-soluble salts of DHF underwent self-condensation to afford the threo diastereomer of pentulosonic acid, through differing reaction pathways contingent on the metal salt used. This transformation exemplifies the diverging roles of DHF as a nucleophile (a synthon for α-hydroxyacetyl anion) and an electrophile (an α-carboxyglycolaldehyde equivalent).

ABSTRACT:The kinetics of the miniemulsion copolymerization of styrene (St) and butyl acrylate (BA) initiated by redox initiators, (NH 4 ) 2 S 2 O 8 /NaHSO 3 , at lower temperature (45°C) was studied. The polymerization rate in miniemulsion copolymerization is lower than that of the corresponding conventional emulsion copolymerization. In regard to the rate of polymerization, the initiator concentration plays a more important role in miniemulsion copolymerization than in conventional emulsion polymerization, while the surfactant concentration has a more important role in conventional emulsion polymerization than in miniemulsion polymerization. These are attributed to their different nucleation mechanisms, which are the same as those found in the miniemulsion polymerization carried out at higher temperatures. While by eliminating nucleation via micelle and ensuring against homogeneous nucleation, miniemulsion polymerization can be carried out by the sole nucleation mechanism-monomer droplet nucleation-at lower temperature. Because of this, the particles become narrower during the polymerization and, finally, monodisperse polymer particles are obtained. The result of the particle numbers indicated that a continuous nucleation will cease at about 60% conversion.