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Correction: 10.1021/acs.joc.1c02513. The tear film lipid layer (TFLL) that covers the ocular surface contains several unique lipid classes, including O-acyl-omega-hydroxy fatty acids, type I-St diesters, and type II diesters. While the TFLL represents a unique biological barrier that plays a central role in stabilizing the entire tear film, little is known about the properties and roles of individual lipid species. This is because their isolation from tear samples in sufficient quantities is a tedious task. To provide access to these species in their pure form, and to shed light on their properties, we here report a general strategy for the synthesis and structural characterization of these lipid classes. In addition, we study the organization and behavior of the lipids at the air-tear interface. Through these studies, new insights on the relationship between structural features, such as number of double bonds and the chain length, and film properties, such as spreading and evaporation resistance, were uncovered.

Antimicrobial resistance is declared by the World Health Organization (WHO) as one of the top 10 threats to global public health, causing thousands of deaths each year. consequently, the search for new drugs is necessary among actions to combat antimicrobial resistance. Cinnamic derivatives stand out for their synthetic simplicity and wide potential for pharmacological activities, including antimicrobial activity. That way, the present work describes the synthesis of four series of diesters cinnamic derivatives, 2-alkyl-2-oxo-(E)-ethyl cinnamates, through the junction between potassium cinnamate salts with 2-chloroacetate esters, and in vitro antimicrobial assays were performed, evaluating the antibacterial, antifungal and antituberculosis activities. The diesters were obtained with yields between 71-98% and characterized by infrared (IR), nuclear magnetic resonance (NMR) hydrogen (1H) and carbon (13C) APT spectroscopic techniques. The minimum inhibitory concentration (MIC) values obtained from the tests were used to establish structure-activity relationships between the type of substituents in the aromatic ring (R: H, 3-NO2, 3,4-OMe and 3-F) and carbon chains alkyls (R': methyl, ethyl, propyl, isopropyl, butyl, sec-butyl and isobutyl) with inhibition activities against the tested microorganisms. Unsubstituted diesters exhibited ample antibacterial activity, with emphasis on Ethyl-2-ethoxy-2-oxo-(E)-cinnamate (1B) compound that had lowest MIC (32 μg mL-1) against Staphylococcus epidermidis ATCC-12288 and, antifungal activity, for compounds with small alkyl chains, against Aspergillus flavus strains LM-248 and ATCC-13013 (258 μg ml-1). Diesters with nitro and dimethoxy substituents were more selective for Proteus mirabilis ATCC-25933 (1024 μg mL-1), Trichophyton rubrum ATCC-28188 (128 μg mL-1) and Aspergillus flavus LM-248 (1024 μg mL-1) strains. Diesters with fluorine substituents exhibited ample antifungal activity with MIC = 1024 μg mL-1, but the increase in alkyl chain makes them inactive. The antituberculosis activity was little influenced by the substituents on the aromatic ring, but all active compounds against Mycobacterium tuberculosis H37Ra with MIC = 250-500 μM have alkyl chains of four carbon atoms. Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES A resistência antimicrobiana é declarada pela Organização Mundial da Saúde (OMS) como uma das 10 principais ameaças à saúde pública global, causando milhares de mortes por ano. Consequentemente, a busca de novos fármacos faz-se necessário dentre as ações de combate a resistência antimicrobiana. Os derivados cinâmicos se destacam pela simplicidade sintética e amplo potencial de atividades farmacológicas, dentre elas, a atividade antimicrobiana. Nesse sentido, o presente trabalho descreve a síntese de quatro séries de diésteres derivados cinâmicos, 2-alquil-2-oxo-(E)-cinamatos de etila, através da junção entre sais de cinamato de potássio com ésteres 2-cloroacetato, e realizados ensaios antimicrobianos in vitro avaliando as atividades antibacteriana, antifúngica e antituberculose. Os diésteres foram obtidos com rendimentos entre 71-98% e caracterizados pelas técnicas espectroscópicas de infravermelho (IV), ressonância magnética nuclear (RMN) de hidrogênio (1H) e carbono (13C) APT. Os valores de concentração inibitória mínima (CIM) obtidos dos ensaios foram usados para estabelecer relações estrutura-atividade entre tipo de substituintes no anel aromático (R: H, 3-NO2, 3,4-OMe e 3-F) e cadeias carbônicas alquílicas (R’: metila, etila, propila, isopropila, butila, sec-butila e isobutila) com as atividades de inibição frente aos micro-organismos testados. Os diésteres não substituídos exibiram ampla atividade antibacteriana, com ênfase ao composto 2-etóxi-2-oxo-(E)-cinamato de etila (1B) que apresentou a menor CIM (32 μg mL-1) contra Staphylococcus epidermidis ATCC-12288 e, atividade antifúngica, para os compostos com cadeias alquílicas pequenas, contra as cepas Aapergillus flavus LM-248 e ATCC-13013 (258 μg mL-1). Os diésteres com substituintes nitro e dimetóxi mostraram-se mais seletivos para as cepas Proteus mirabilis ATCC-25933 (1024 μg mL-1), Trichophyton rubrum ATCC-28188 (128 μg mL-1) e Aspergillus flavus LM-248 (1024 μg mL-1). Os diésteres com substituintes flúor exibiram ampla atividade antifúngica com CIM = 1024 μg mL-1, porém o aumento da cadeia alquílica os tornam inativos. A atividade antituberculose foi pouco influenciada pelos substituintes no anel aromático, mas todos os compostos ativos frente a Mycobacterium tuberculosis H37Ra com CIM = 250-500 μM possuem cadeias alquílicas de quatro átomos de carbono.

Black pepper (Piper nigrum L.) is the most consumed spice in the world, being a fruit of great economic and pharmaceutical importance. The beneficial physiological effects of black pepper, such as: relief of pain and chills, treatment of colds and flu, rheumatism, among others, are attributed to its main active ingredient, piperine. This, in turn, has a wide spectrum of biological activities and has been playing an important role as a raw material for the synthesis of new compounds with pharmacological interest. The objective of this research was the use of piperine, extracted from black pepper, as a precursor in the synthesis of new derived molecules, in order to evaluate the antimicrobial and antitumor potential of these compounds. Initially, two series of substituted chloro-esters and the salt of piperic acid were planned and synthesized as intermediates, which were submitted to a nucleophilic bimolecular substitution reaction (SN2) giving rise to 30 new diesters derived from piperine. The final compounds showed yields between 50 and 84% and were characterized by infrared (IR) spectroscopic techniques, 1H and 13C nuclear magnetic resonance (NMR) and 2D NMR (COSY, HSQC, HMBC). The biological potential of the final compounds were evaluated through the in silico study, in vitro antimicrobial activity, acute non-clinical toxicity and in vivo antitumor activity. In the in silico study, only the compounds Butyl 4-(4-iodobenzoate)- piperate (DE-05) and Butyl 4-(3,5-dinitrobenzoate)-piperate (DE-08) violated two of the Lipinski parameters, therefore, it can be inferred that the other compounds must present a good oral bioavailability. In the in vitro antimicrobial evaluation, bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), yeast fungi (Candida albicans and C. tropicalis) and filamentous fungi (Aspergillus fumigatus, A. flavus and A. niger) were used. The result of the evaluation of the final compounds showed that the substance Butyl 4-(4- methylbenzoate)-piperate (DE-06) presented a more comprehensive antimicrobial action, managing to inhibit several strains with a minimum inhibitory concentration (MIC) of 256 µg/ml. Most of all substances were effective against yeast fungi, and only a small portion of these substances were also effective against filamentous fungi. However, none of the final products had antibacterial activity. The compound 4-(4-nitro-benzoate)-butyl piperate (DE 07) was submitted to acute non-clinical toxicity tests, the lethal dose (LD50) was estimated at 1000 mg/kg, being considered a low compound acute toxicity. The result of the evaluation of the in vivo antitumor effect of the compound DE-07, in an Ehrlich ascitic carcinoma (EAC) model, showed a significant reduction in the tumor mass and in the parameters of viability and total cell; such results allow us to infer that the compound, in the experimental model evaluated, has significant antitumor activity in vivo. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Fundação de Apoio à Pesquisa do Estado da Paraíba - FAPESQ A pimenta-do-reino (Piper nigrum L.) é a especiaria mais consumida no mundo, sendo um fruto de grande importância econômica e farmacêutica. Os efeitos fisiológicos benéficos da pimenta-do-reino, tais como: alívio da dor e calafrios, tratamento de gripes e resfriados, reumatismo, entre outros, são atribuidos ao seu principal princípio ativo, a piperina. Esta, por sua vez, possui um amplo espectro de atividades biológicas e vem desempenhando um importante papel como matéria-prima para a síntese de novos compostos com interesse farmacológico. O objetivo desta pesquisa foi a utilização da piperina, extraída da pimenta-do reino, como precursor na síntese de novas moléculas derivadas, a fim de avaliar a potencialidade antimicrobiana e antitumoral destes compostos. Inicialmente, foram planejados e sintetizados como intermediários duas séries de cloro-ésteres substituídos e o sal do ácido pipérico, os quais foram submetidos a reação de substituição nucleofílica bimolecular (SN2) dando origem a 30 novos diésteres derivados da piperina. Os compostos finais apresentaram rendimentos entre 50 e 84% e foram caracterizados por técnicas espectroscópicas de infravermelho (IV), ressonância magnética nuclear (RMN) de 1H e 13C e RMN 2D (COSY, HSQC, HMBC). A potencialidade biológica dos compostos finais foram avaliadas através do estudo in silico, atividade antimicrobiana in vitro, toxicidade não clinica aguda e atividade antitumoral in vivo. No estudo in silico, apenas os compostos 4-(4-iodo-benzoato)-piperato de butila (DE-05) e 4-(3,5-dinitro-benzoato)-piperato de butila (DE-08) violaram dois dos parâmetros de Lipinski, portanto, pode-se inferir que os demais compostos devem apresentar uma boa biodisponibilidade oral. Na avaliação antimicrobiana in vitro foram utilizadas cepas de bactérias (Staphylococcus aureus e Pseudomonas aeruginosa), fungos leveduriformes (Candida albicans e C. tropicalis) e fungos filamentosos (Aspergillus fumigatus, A. flavus e A. niger). O resultado da avaliação dos compostos finais mostrou que a substância 4-(4-metil benzoato)-piperato de butila (DE-06) apresentou ação antimicrobiana mais abrangente, conseguindo inibir várias cepas com uma concentração inibitória mínima (CIM) de 256 g/mL. Boa parte de todas as substâncias se mostrou eficaz contra os fungos leveduriformes, e apenas uma pequena parcela dessas substâncias foi eficaz também contra os fungos filamentosos. Contudo, nenhum dos produtos finais apresentou atividade antibacteriana. O composto 4-(4-nitro-benzoato)-piperato de butila (DE-07) foi submetido a ensaios de toxicidade não clínica aguda, a dose letal (DL50) foi estimada em 1000 mg/kg, sendo considerado um composto de baixa toxicidade aguda. O resultado da avaliação do efeito antitumoral in vivo do composto DE-07, em modelo de carcinoma ascítico de Ehrlich (CAE), mostrou uma redução significativa da massa tumoral e dos parâmetros de viabilidade e total celular; tais resultados permitem inferir que o composto, no modelo experimental avaliado, apresenta significativa atividade antitumoral in vivo.

The degradation of acetal derivatives of the diethylester of galactarate (GalX) was in vestigated by electron paramagnetic resonance (EPR) spectroscopy in the context of solvent-free, high-temperature reactions like polycondensations. It was demonstrated that less substituted cyclic acetals are prone to undergo radical degradation at higher temperatures as a result of hydrogen abstraction. The EPR observations were supported by the synthesis of GalX based polyamides via ester-amide exchange-type polycondensations in solvent-free conditions at high temperatures in the presence and in the absence of radical inhibitors. The radical degradation can be offset by the addition of a radical inhibitor. The radical is probably formed on the methylene unit between the oxygen atoms and subsequently undergoes a rearrangement. ispartof: Molecules vol:26 issue:19 ispartof: location:Switzerland status: published

Esters present several advantages when compared to traditional materials used for thermal energy storage, amongst which are better sustainability and greater chemical stability. However, at present, their thermal properties remain mostly unknown or not well documented. In this study, 12 diesters from four dicarboxylic acids (oxalic, succinic, suberic, sebacic) and three alcohols (methanol, 1-pentanol, 1-decanol) have been assessed as bio-based phase change materials for thermal energy storage. All diesters have been synthesized via Fischer esterification to high purities, and their chemical structures, as well as thermal properties, have been fully characterized. The diesters investigated show phase change transitions in a low&ndash, mid temperature range between -32 and 46 &deg, C with maximum enthalpies of 172 J/g and show higher degrees of supercooling compared to fatty monoesters. Similarly to other esters classes, some trends correlating the chemical structures to the thermal properties were identified, which would allow for the development of property prediction tools.

We sampled ammonium sulfate particles and indoor particles of outdoor origin through a small chamber covered with polyvinyl chloride flooring. We measured the uptake of semivolatile organic compounds (SVOCs) by the airborne particles in real time. The particles acquired SVOC mass fractions up to 10%. The phthalate ester (di(2-ethylhexyl)-phthalate) (DEHP), a known endocrine disruptor, contributed by approximately half of the sorbed SVOC mass. The indoor particles acquired a higher DEHP fraction than laboratory-generated ammonium sulfate aerosol. We attribute this increased uptake to absorption by organic matter present in the indoor particles. Using a thermodenuder to remove volatile components, predominantly organics, reduced the SVOC uptake. Positive matrix factorization applied to the organic mass spectra suggests that hydrocarbon-like organic aerosol (typically fresh traffic exhaust) sorbs DEHP more efficiently than aged organic aerosol. The SVOC uptake is one of the processes that modify outdoor pollution particles after they penetrate buildings, where the majority of exposure occurs. Particles from indoor sources, typically dominated by organic matter, will undergo such processes as well. Aerosol mass spectrometry improves the time resolution of experimental investigations into these processes and enables experiments with lower, relevant particle concentrations. Additionally, particle size-resolved results are readily obtained.

A series of fifteen new piperine-derived diesters was synthesized through the substitution reaction between the salt of piperic acid, obtained through piperine basic hydrolysis, with the δ-chloro-esters, obtained through the cleavage of tetrahydrofuran (THF) with acyl chlorides in the presence of ZnCl2. The final compounds were obtained with yields ranging from 50 to 84% and were characterized by infrared (IR) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR). The new compounds were evaluated in silico in regard to their ADME (absorption, distribution, metabolism, and excretion) properties, and in vitro for their antimicrobial activity against bacteria strains (Staphylococcus aureus and Pseudomonas aeruginosas), yeast fungi (Candida albicans and C. tropicalis) and filamentous fungi (Aspergillus fumigatus, A. flavus and A. niger). The results from the in silico studies of Lipinski’s rule of five showed that most compounds present good pharmacological possibilities, and the results from in vitro antimicrobial activity showed that 8 of the 15 synthesized compounds displayed antimicrobial activity, inhibiting the growth of 40-80% of tested strains, with a minimum inhibitory concentration (MIC) interval ranging from 1024 to 256 µg mL−1.

Piperine, previously extracted from black pepper (Piper nigrum L.), was used as a precursor for the synthesis of twelve new diester derivatives. The final products were obtained through the bimolecular nucleophilic substitution reaction (SN2) of the alkyl 2-chloroacetates and the salt of piperic acid, obtained from the basic hydrolysis of piperine. The compounds were synthesized with yields of 55-84% and characterized by infrared spectroscopy and 1H and 13C nuclear magnetic resonance. The evaluation of the compounds’ potential as new drug candidates was done through an in silico study of ADME properties (absorption, distribution, metabolization and excretion) and evaluation of antimicrobial activity against bacterial strains (Staphylococcus aureus and Pseudomonas aeruginosa), yeasts (Candida albicans and Candida tropicalis) and filamentous fungi (Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger). The in silico study showed that the compounds were good drug candidates and antimicrobial evaluation demonstrated that 9 of the 12 compounds exhibited a minimum inhibitory concentration (MIC) ranging 1024-256 μg mL-1.

International audience; The first non-natural derivative of the rare D-glucose-2-phosphate (G2P), namely glucose-2-(O-lactic acid phosphate) (G2LP), has been synthesized. When used as sole carbon source, G2LP enables bacterial growth of the plant pathogenic strain Agrobacterium fabrum C58 (formerly referred to as Agrobacterium tumefa-ciens). X-ray crystallography and affinity measurements investigations reveal that G2LP binds the periplasmic binding protein (PBP) AccA similarly to the natural compounds and with the same affinity. Moreover, enzy-matic assays show that it is able to serve as substrate of the phosphodiesterase AccF. The properties found for G2LP demonstrate that the very unusual glucose-2-phosphoryl residue, present in G2LP, can be used as structural feature for designing non-natural systems fully compatible with the Acc cascade of A. fabrum.

The use of natural resources as a chemical feedstock for the synthesis of added-value products is gaining interest; as such we report an environmentally friendly method for the synthesis of para-menthane-3,8-diol from natural citronellal oil in 96% yield, under solvent free aqueous conditions. The acylation of para-menthane-3,8-diol with various acid anhydrides over polymer-supported scandium triflate (PS-Sc(OTf)3) catalyst was subsequently developed, where both hydroxy groups of para-menthane-3,8-diol could be simultaneous acylated under mild reaction conditions to form the corresponding diesters in good yields. The advantages of this method include a simple procedure from natural resources, using solvent-free reaction conditions.

[Abstract] Electroreduction of diesters [R1COO(CH2)2OCOR2] with Mg electrode has been found to give the corresponding unsymmetrical 1,2-diketones (R1COCOR2) with excellent yields.

A systematic study for esterification procedures to the synthesis of BINOL diesters is described. Reaction conditions with TFAA and 85% H3PO4 were selected as the best procedure to prepare enantiomerically pure (S)-BINOL diesters VIII to XI with almost quantitative yields and very low reaction times. Fil: Costantino, Andrea Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Ocampo, Romina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Fernández, Gustavo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Koll, Liliana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Mandolesi, Sandra Delia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina

Three zirconium(IV) complexes (1-3) with mono- and dinucleating tripodal ligands are reported that promote the hydrolysis of the phosphate monoesters p-nitrophenyl phosphate (NPP) and phenyl phosphate (PP) in neutral solution. At pH 7 up to 10(4)- and 10(6)-fold rate accelerations of the hydrolysis of NPP and PP are observed. A detailed kinetic study has been carried out for NPP. The complexes show Michaelis-Menten behavior, k(cat) and 1/K-m values at pH 7.0, 25 degrees C are 2.7 x 10(-5) s(-1) and 806 M-1 (1), 1.1 x 10(-4) s(-1) and 556 M-1 (2) and 1.1 x 10(-4) s(-1) and 565 M-1 (3). Entropies of activation of -92.0 J K-1 mol(-1) (1), -75.6 J K-1 mol(-1) (2) and -98.6 J K-1 mol(-1) (3) are consistent with an associative mechanism. peer-reviewed

In this study we present our efforts to homo- and co-polymerize, using group transfer polymerization (GTP), a dialkyl diester of itaconic acid, a naturally-derived unsaturated dicarboxylic acid. The monomer employed, di(n-butyl) itaconate (DBI), did not seem to polymerize by GTP to high conversion, but it displayed the remarkable ability to contribute to the polymer 1-2 units, suggesting that it would make a good end-functionalizing reagent for GTP. This was demonstrated by preparing by GTP hydrophilic homopolymers, and in situ adding to them DBI which is hydrophobic. The thus-obtained amphiphilic end-functionalized copolymers formed in water small micelles, whose aggregation numbers and radii of gyration were characterized using small-angle neutron scattering. © 2010 Elsevier Ltd. All rights reserved. 47 4 816 822 Cited By :9

Two series of diesters with bend-rod shapes were synthesized and their thermal properties characterized by POM and DSC. The central group conformational mobility and polarity as well as the length of the mesogenic groups were varied in order to correlate these parameters with mesophase stability. Results indicate that series II diesters are enantiotropic and that their mesophase sensitivity to central group structural changes is limited.

Molecular structure of [Cu(dtbp)(2)(phen)(OH2)] (dtbp- H = di-tert-butylphosphate, phen = 1,10-phenanthroline), determined at 293, 203 and 93 K, provides useful snap-shots of O-H bond activation of a metal-bound water, which is aided by an intramolecular P=O...H-O hydrogen bonding interaction.