Showing papers on "Carboxylic acid published in 2013"

Large-Scale Production of Edge-Selectively Functionalized Graphene Nanoplatelets via Ball Milling and Their Use as Metal-Free Electrocatalysts for Oxygen Reduction Reaction

Abstract: Edge-selectively functionalized graphene nanoplatelets (EFGnPs) with different functional groups were efficiently prepared simply by dry ball milling graphite in the presence of hydrogen, carbon dioxide, sulfur trioxide, or carbon dioxide/sulfur trioxide mixture. Upon exposure to air moisture, the resultant hydrogen- (HGnP), carboxylic acid- (CGnP), sulfonic acid- (SGnP), and carboxylic acid/sulfonic acid- (CSGnP) functionalized GnPs readily dispersed into various polar solvents, including neutral water. The resultant EFGnPs were then used as electrocatalysts for oxygen reduction reaction (ORR) in an alkaline electrolyte. It was found that the edge polar nature of the newly prepared EFGnPs without heteroatom doping into their basal plane played an important role in regulating the ORR efficiency with the electrocatalytic activity in the order of SGnP > CSGnP > CGnP > HGnP > pristine graphite. More importantly, the sulfur-containing SGnP and CSGnP were found to have a superior ORR performance to commerciall...

Carboxylic Acid (Bio)Isosteres in Drug Design

Abstract: The carboxylic acid functional group can be an important constituent of a pharmacophore, however, the presence of this moiety can also be responsible for significant drawbacks, including metabolic instability, toxicity, as well as limited passive diffusion across biological membranes. To avoid some of these shortcomings while retaining the desired attributes of the carboxylic acid moiety, medicinal chemists often investigate the use of carboxylic acid (bio)isosteres. The same type of strategy can also be effective for a variety other purposes, for example, to increase the selectivity of a biologically active compound or to create new intellectual property. Several carboxylic acid isosteres have been reported, however, the outcome of any isosteric replacement cannot be readily predicted as this strategy is generally found to be dependent upon the particular context (i.e., the characteristic properties of the drug and the drug–target). As a result, screening of a panel of isosteres is typically required. In this context, the discovery and development of novel carboxylic acid surrogates that could complement the existing palette of isosteres remains an important area of research. The goal of this Minireview is to provide an overview of the most commonly employed carboxylic acid (bio)isosteres and to present representative examples demonstrating the use and utility of each isostere in drug design.

Catalytic transformation of alcohols to carboxylic acid salts and H2 using water as the oxygen atom source

Abstract: The development of a catalytic, mild and atom-economical transformation of alcohols to carboxylic acid salts and hydrogen gas is described. The reaction uses water as a source of oxygen, with a homogenous Ru catalyst at low (0.2 mol%) catalyst loadings in basic aqueous solution.

Asymmetric epoxidation with H2O2 by manipulating the electronic properties of non-heme iron catalysts.

Abstract: A non-heme iron complex that catalyzes highly enantioselective epoxidation of olefins with H2O2 is described. Improvement of enantiomeric excesses is attained by the use of catalytic amounts of carboxylic acid additives. Electronic effects imposed by the ligand on the iron center are shown to synergistically cooperate with catalytic amounts of carboxylic acids in promoting efficient O–O cleavage and creating highly chemo- and enantioselective epoxidizing species which provide a broad range of epoxides in synthetically valuable yields and short reaction times.

Manipulating Catalytic Pathways: Deoxygenation of Palmitic Acid on Multifunctional Catalysts

Abstract: The mechanism of the catalytic reduction of palmitic acid to n-pentadecane at 260 degrees C in the presence of hydrogen over catalysts combining multiple functions has been explored. The reaction involves rate-determining reduction of the carboxylic group of palmitic acid to give hexadecanal, which is catalyzed either solely by Ni or synergistically by Ni and the ZrO2 support. The latter route involves adsorption of the carboxylic acid group at an oxygen vacancy of ZrO2 and abstraction of the alpha-H with elimination of O to produce the ketene, which is in turn hydrogenated to the aldehyde over Ni sites. The aldehyde is subsequently decarbonylated to n-pentadecane on Ni. The rate of deoxygenation of palmitic acid is higher on Ni/ZrO2 than that on Ni/SiO2 or Ni/Al2O3, but is slower than that on H-zeolite-supported Ni. As the partial pressure of H-2 is decreased, the overall deoxygenation rate decreases. In the absence of H-2, ketonization catalyzed by ZrO2 is the dominant reaction. Pd/C favors direct decarboxylation (-CO2), while Pt/C and Raney Ni catalyze the direct decarbonylation pathway (-CO). The rate of deoxygenation of palmitic acid (in units of mmol mol(total metal)(-1) h(-1)) decreases in the sequence r((Pt black)) approximate to r((Pd black)) > r((Raney Ni)) in the absence of H-2. In situ IR spectroscopy unequivocally shows the presence of adsorbed ketene (C=C=O) on the surface of ZrO2 during the reaction with palmitic acid at 260 degrees C in the presence or absence of H-2.

Scope and Limitations of Auxiliary-Assisted, Palladium-Catalyzed Arylation and Alkylation of sp2 and sp3 C–H Bonds

Abstract: The scope of palladium-catalyzed, auxiliary-assisted direct arylation and alkylation of sp2 and sp3 C–H bonds of amine and carboxylic acid derivatives has been investigated. The method employs a palladium acetate catalyst, substrate, aryl, alkyl, benzyl, or allyl halide, and inorganic base in tert-amyl alcohol or water solvent at 100–140 °C. Aryl and alkyl iodides as well as benzyl and allyl bromides are competent reagents in this transformation. The picolinic acid auxiliary is used for amine γ-functionalization, and the 8-aminoquinoline auxiliary is used for carboxylic acid β-functionalization. Some optimization of base, additives, and solvent is required for achieving best results.

Growth of Highly Fluorescent Polyethylene Glycol- and Zwitterion-Functionalized Gold Nanoclusters

Abstract: We have prepared and characterized a new set of highly fluorescent gold nanoclusters (AuNCs) using one-step aqueous reduction of a gold precursor in the presence of bidentate ligands made of lipoic acid anchoring groups, appended with either a poly(ethylene glycol) short chain or a zwitterion group. The AuNCs fluoresce in the red to near-infrared region of the optical spectrum with emission centered at ∼750 nm and a quantum yield of ∼10-14%, and they exhibit long fluorescence lifetimes (up to ∼300 ns). Dispersions of these AuNCs exhibit great long-term colloidal stability, over a wide range of pHs (2-13) and in the presence of high electrolyte concentrations, and a strong resistance to reducing agents such as glutathione. The growth strategy further permitted the controlled, in situ functionalization of the NCs with reactive groups (e.g., carboxylic acid or amine), making these nanoclusters compatible with common and simple-to-implement coupling strategies, such as carbodiimide chemistry. These properties combined make these fluorescent NCs greatly promising for use in various imaging and sensing applications where NIR and long-lived excitations are desired.

Transition metal-catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids

Abstract: The decarboxylative coupling of alkynyl carboxylic acids is an attractive area of research in organic chemistry, because the structure of aryl alkyne is one of the important building blocks for the synthesis of p-conjugated compounds. The use of alkynyl carboxylic acid as an alkyne source has several advantages in handling and storage. As a catalyst, palladium, copper, nickel, and silver were employed in the decarboxylative coupling reactions. The formation of C–C (sp2–sp, sp–sp and sp3–sp), C–N, C–P and C–S bonds has been developed. This review aims to illustrate the development of the decarboxylative coupling reaction of alkynyl carboxylic acids.

Copper Nanoparticles: Aqueous Phase Synthesis and Conductive Films Fabrication at Low Sintering Temperature

Abstract: Conductive copper nanoinks can be used as a low-cost replacement for silver and gold nanoinks that are used in inkjet printing of conductive patterns. We describe a high-throughput, simple, and convenient method for the preparation of copper nanoparticles in aqueous solution at room temperature. Copper acetate is used as the precursor, hydrazine as the reducing agent, and short chain carboxylic acids as capping agents. The concentration of the carboxylic acid plays a key role in the preparation of such copper nanoparticles. Stable copper nanoparticles with a diameter of less than 10 nm and a narrow size distribution were prepared when high concentrations of lactic acid, citric acid, or alanine were used. Thermogravimetric analysis results showed that any lactic acid or glycolic acid adsorbed on the surface of the copper nanoparticles can be removed at a relatively low temperature, especially, glycolic acid, which can be removed from the surface at about 125 °C. Highly conductive copper films prepared using lactic acid and glycolic acid as capping agents were obtained by drop coating a copper nanoparticle paste onto a glass slide followed by low temperature sintering. The electrical resistivity of the copper film using glycolic acid as the capping agent was 25.5 ± 8.0 and 34.8 ± 9.0 μΩ·cm after annealing at 150 and 200 °C for 60 min under nitrogen, respectively. When lactic acid was used as the capping agent, the electrical resistivity of the copper films was 21.0 ± 7.0 and 9.1 ± 2.0 μΩ·cm after annealing at 150 and 200 °C for 60 min under nitrogen, respectively, with the latter being about five times greater than the resistivity of bulk copper (1.7 μΩ·cm).

Fast Hydrazone Reactants: Electronic and Acid/Base Effects Strongly Influence Rate at Biological pH

Abstract: Kinetics studies with structurally varied aldehydes and ketones in aqueous buffer at pH 7.4 reveal that carbonyl compounds with neighboring acid/base groups form hydrazones at accelerated rates. Similarly, tests of a hydrazine with a neighboring carboxylic acid group show that it also reacts at an accelerated rate. Rate constants for the fastest carbonyl/hydrazine combinations are 2-20 M(-1) s(-1), which is faster than recent strain-promoted cycloaddition reactions.

Small Molecule- and Amino Acid-Induced Aggregation of Gold Nanoparticles

Abstract: To understand which organic molecules are capable of binding to gold nanoparticles and/or inducing nanoparticle aggregation, we investigate the interaction of gold nanoparticles with small molecules and amino acids at variable pH. Dynamic Light Scattering (DLS) and ultraviolet-visible (UV-vis) spectra were measured on mixtures of colloidal gold with small molecules to track the progression of the aggregation of gold nanoparticles. We introduce the 522 to 435 nm UV–vis absorbance ratio as a sensitive method for the detection of colloidal gold aggregation, whereby we delineate the ability of thiol, amine, and carboxylic acid functional groups to bind to the surfaces of gold nanoparticles and investigate how combinations of these functional groups affect colloidal stability. We present models for mechanisms of aggregation of colloidal gold, including surface charge reduction and bridging linkers. For all molecules whose addition leads to the aggregation of gold nanoparticles, the aggregation kinetics were ac...

Highly Selective Hydroxylation of Benzene to Phenol by Wild-type Cytochrome P450BM3 Assisted by Decoy Molecules

Abstract: Phenol is a key intermediate in industry for the synthesis of drugs, dyes, and functional polymers. Because phenol is currently produced by the cumene process, which involves high energy consumption and significant formation of side products such as acetone and methylstyrene, direct hydroxylation of benzene has attracted much attention as an alternative method of production. The direct hydroxylation of benzene to phenol using a variety of catalysts, electrochemical oxidation systems, and photochemical systems has thus been extensively investigated. In contrast to many oxidation reactions at high temperature, monooxygenases in nature, such as cytochrome P450, efficiently catalyze the oxidation of inert alkanes and aromatic compounds under mild conditions. Thus, various engineered enzymes have been constructed by site-directed mutagenesis, random mutagenesis, and chemical modification. Biocatalysts for exclusive hydroxylation of the benzene ring using natural enzymes, if they could be developed, would be ideal systems for the production of phenol. Herein we report an efficient and selective hydroxylation of benzene to phenol catalyzed by wild-type cytochrome P450BM3 (P450BM3) with the assistance of decoy molecules. We and Zilly et al. have recently developed a simple and unique system for the hydroxylation of gaseous alkanes, such as propane and butane, catalyzed by wild-type P450BM3. Wild-type P450BM3 exclusively catalyzes the hydroxylation of long-alkyl-chain fatty acids and never hydroxylates small alkanes, because the active site of P450BM3 is optimized for the hydroxylation of fatty acids (Figure 1a, upper) and the first step of the catalytic cycle of P450BM3 starts only when a fatty acid binds to the substrate binding site of P450BM3, which is accompanied by the removal of the water molecule coordinated to the heme iron (Figure 1b, left). However, in the presence of perfluorinated carboxylic acids (PFCs) as inert dummy substrates (decoy molecules), gaseous alkanes can be hydroxylated by wild-type P450BM3. The decoy molecules initiate the activation of molecular oxygen in the same manner as long-alkyl-chain fatty acids and induce the generation of compound I (Figure 1b, right). Because the C F bonds of PFCs are not oxidizable, compound I exclusively hydroxylates gaseous alkanes. Moreover, shortalkyl-chain PFCs partially occupy the substrate binding site of P450BM3 to afford a space for small alkanes, which leads to efficient hydroxylation of the small alkanes (Figure 1a, lower). This attractive advantage encouraged us to perform benzene hydroxylation for the selective production of phenol. The hydroxylation of benzene by P450BM3 was examined by employing a series of PFCs (PFC8–PFC12; Table 1). The catalytic turnover rates of phenol formation were very much

Catalytic enantioselective difluoroalkylation of aldehydes.

Abstract: Copper-catalyzed bond scission of pentafluorobutane-1,3-diones generates difluoroenolates that react with aldehydes to give a wide range of chiral α,α-difluoro-β-hydroxy ketones within a few hours in up to 99 % yield and 92 % ee. The synthetic utility of this reaction is demonstrated with the stereoselective synthesis of a chiral anti-1,3-diol exhibiting a central difluoromethylene unit and efficient conversion to a 2,2-difluoro-3-hydroxy carboxylic acid.

Hydrogenation of carboxylic acids catalyzed by half-sandwich complexes of iridium and rhodium.

Abstract: A series of half-sandwich Ir and Rh compounds are demonstrated to be competent catalysts for the hydrogenation of carboxylic acids under relatively mild conditions. Of the structurally diverse group of catalysts tested for activity, a Cp*Ir complex supported by an electron-releasing 2,2'-bipyridine ligand was the most active. Higher activity was achieved with employment of Bronsted or Lewis acid promoters. Mechanistic studies suggest a possible reaction pathway involving activated carboxylic acid substrates. The hydrogenation reaction was shown to be general to a variety of aliphatic acids.

Carboxylic Acid (Bio)Isosteres in Drug Design

Abstract: The carboxylic acid functional group can be an important constituent of a pharmacophore, however, the presence of this moiety can also be responsible for significant drawbacks, including metabolic instability, toxicity, as well as limited passive diffusion across biological membranes. To avoid some of these shortcomings while retaining the desired attributes of the carboxylic acid moiety, medicinal chemists often investigate the use of carboxylic acid (bio)isosteres. The same type of strategy can also be effective for a variety other purposes, for example, to increase the selectivity of a biologically active compound or to create new intellectual property. Several carboxylic acid isosteres have been reported, however, the outcome of any isosteric replacement cannot be readily predicted as this strategy is generally found to be dependent upon the particular context (i.e., the characteristic properties of the drug and the drug–target). As a result, screening of a panel of isosteres is typically required. In this context, the discovery and development of novel carboxylic acid surrogates that could complement the existing palette of isosteres remains an important area of research. The goal of this Minireview is to provide an overview of the most commonly employed carboxylic acid (bio)isosteres and to present representative examples demonstrating the use and utility of each isostere in drug design.

General and Practical Carboxyl-Group-Directed Remote C–H Oxygenation Reactions of Arenes

Abstract: Transition-metal-catalyzed aromatic C–H oxygenation reaction[1] is a very powerful tool for straightforward synthesis of valuable oxygen-containing products from abundant arenes.[2] Of these reactions, intramolecular C–H/O–H oxidative coupling of carboxylic acid with unactivated sp2 C–H bond is an important transformation, because it gives an access to a variety of valuable lactone-containing molecules.[3] Thus, 3,4-benzocoumarin fragment 2, containing six-membered lactone moiety, is widely found in natural and bioactive molecules, as well as in useful materials.[4] Expectedly, 2 can be accessed through cyclization of nonpre-functionalized 2-arylbenzoic acids 1; however, the existing methods require either employment of stoichiometric amounts of toxic oxidants[5] or UV irradiation,[6] which substantially limits applicability of these methods (Scheme 1). We hypothesized that it should be possible to develop a general, practical, and environmentally benign dehydrogenative C–H/O–H lactonization reaction of 2-arylbenzoic acids 1 into 3,4-benzocoumarins 2 en route to oxygenated biaryls 3. We envisioned that C–H oxygenation could potentially be performed by formation of carboxyl O-centered radical A, which would undergo a subsequent C–O bond formation.[7] Scheme 1 Carboxyl-group-directed C–H oxygenation reactions. Herein, we report two complimentary methods for this transformation. Method 1, the Cu-catalyzed oxygenation reaction of 2-arylbenzoic acids, which is efficient for electron-neutral and electron-rich substrates. During preparation of this manuscript, a similar to Method 1 Cu-catalyzed transformation was disclosed by Gallardo-Donaire and Martin.[8] Most importantly, we also developed a more general and practical Method 2, the K2S2O8-mediated oxygenation reaction, which is widely applicable for cyclization of electron-neutral, electron-rich, as well as electron-deficient substrates. To develop mild and environmentally benign intramolecular lactonization reaction of 2-arylbenzoic acids, we performed extensive screening of transition-metal catalysts and oxidants.[9] It was found that this reaction can efficiently be accomplished by using CuII catalyst. Thus, 2-phenylbenzoic acid 1a was converted into the desired benzocoumarin product 2a in 88% yield in the presence of Cu(OAc)2·H2O (5 mol%) and tert-butyl peroxybenzoate (TBPB, Luperox P) in dichloroethane (Method 1). We found that substrates with electron-neutral and electron-donating substituents, as well as aryl halide fragments (Hal=F, Cl, Br) and cyanogroup on the “guest” aryl ring, produced the desired products in good to excellent yield (Table 1, entries 2a–j). In general, benzoic acids substituted with arene ring containing meta-substituents (F, Cl, OMe, tBu) preferentially underwent cyclization at the less hindered site (Table 1, entries 2k–n). In contrast, meta-Me substituted substrate 1o cyclized at the more hindered site producing 2o as a major regioisomer (4:1).[10] In addition, 2-naphthyl substituted benzoic acid 1p gave the product of cyclization at the more electron-rich 1-position, exclusively (2p). Likewise, substrates containing 3,5-disubstituted arene ring also underwent efficient cyclization into benzocoumarin products 2q and r. 2-Phenylbenzoic acids containing substituents at 1-, 2-, and 3-positions also underwent smooth C–H oxygenation reaction producing products 2s–v. Although electron-neutral and electron-rich substrates under these reaction conditions (Method 1) gave the corresponding benzocoumarins in good to excellent yields, cyclization reaction of electron-deficient substrates was less efficient. Hence, 2-arylbenzoic acids with important electron-withdrawing functional groups, such as CF3 (1w), COMe (1x), and CONMe2 (1y) provided the corresponding products in diminished yields, whereas substrates possessing CHO (1z), CF3 (1aa, ab), and NO2 groups (1ac–ae) produced trace to no product at all (Table 1). Table 1 CuII-catalyzed C–H oxygenation reaction. To overcome this limitation of the Cu-catalyzed oxygenation reaction (Method 1, Table 1), we aimed at the development of a complementary method for cyclization of electron deficient 2-arylbenzoic acids. Delightfully, we found that this transformation can be performed in the presence of K2S2O8 oxidant in aqueous acetonitrile.[11] Thus, benzocoumarin 2a was formed in 93% yield from 2-phenylbenzoic acid 1a in gram-scale manner by using this convenient and environmentally benign protocol (Table 2). We found that Method 2 works efficiently for electron-neutral and electron-deficient substrates under these conditions (entries 2a, i,p, r, t,u). Notably, in the presence of K2S2O8, benzoic acids substituted with arene ring containing meta-substituents produced the corresponding products in higher selectivity compared to that of Method 1 (Table 2, entries 2k–o′). Most importantly, the developed protocol can be successfully applied to a variety of electron-deficient substrates. Accordingly, 2-arylbenzoic acids with CF3 (2w, 2aa), COMe (2x), CONMe2 (2y), and CHO (2z) groups underwent cyclization producing the corresponding products in good to excellent yields. Moreover, previously incompetent substrates with highly electron- withdrawing NO2 group (2ac, 2ad, 2ae) and even two CF3 groups (2ab) now were smoothly transformed into the corresponding benzocoumarin products (Method 1, Table 1). It should be mentioned that in some cases, addition of a catalytic amount of AgNO3 (10 mol%) led to substantial increases of reaction rates.[12, 13] Table 2 K2S2O8-mediated C–H oxygenation reaction. Naturally, the developed methods open access to a variety of densely functionalized benzocoumarin molecules.[4] In addition, considering the importance of aryl ether moiety, we have shown that the obtained 3,4-benzocoumarins could be nearly quantitatively converted into the corresponding biaryl ethers 3 (Scheme 2). Scheme 2 Conversion of lactones into aryl ethers. It is likely that the CuII-catalyzed oxygenation reaction (Method 1) proceeds through an active CuIII intermediate A (Scheme 3), which may abstract the adjacent hydrogen atom to form aryl radical B (Path A). The latter, upon oxidative ring closure, would produce B′, followed by a reductive elimination to form 2.[14, 15] Alternatively, a single-electron transfer (SET) process in A would give radical–cation specie C (Path B), which would be transformed into 2 by a subsequent C–O bond-forming reaction.[16] Scheme 3 Proposed mechanism for Method 1. The K2S2O8-mediated oxygenation reaction (Method 2) most likely proceeds by oxidation of benzoic acid 1 into an O-centered carboxylic radical D, which undergoes addition to the arene ring to form an aryl radical intermediate E (Scheme 4, [Eq. (1)], Path A). The latter converts into the benzocoumarin product 2a upon loss of a hydrogen radical. This homolytic aromatic substitution mechanism is supported by our experiments on cyclization of substrates containing 2-haloaryl substituents 4a–c (G= F, Cl, Br). It was found that these reactions exclusively produce substitution products 2a instead of possible C–H coupling products 5 (Scheme 4, [Eq. (2)]).[17] Alternative mechanism involving an abstraction of hydrogen radical from the aromatic ring in the intermediate D to form the aromatic radical F cannot be ruled out at this stage (Scheme 4, [Eq. (1)], Path B). Scheme 4 Proposed mechanism for Method 2. In conclusion, two complimentary methods for carboxyl-group- directed remote C–H oxygenation reaction of arenes were developed. Method 1, the Cu-catalyzed reaction, produces a variety of 3,4-benzocoumarins containing electron-neutral and electron-releasing substituents. In addition, a more general Method 2, the K2S2O8-mediated transformation, which is widely applicable to various electron-rich and electron-deficient 2-arylbenzoic acids, was developed. This protocol features a broad scope, a good functional group tolerance, and good selectivity. It is also benign, operationally simple, easily scalable, and proceeds under mild conditions.

Role of Acid in Precursor Conversion During InP Quantum Dot Synthesis

Abstract: We have studied the speciation of P(SiMe3)3 during the synthesis of colloidal InP quantum dots in the presence of proton sources. Using 31P NMR spectroscopy, we show H3-nP(SiMe3)n formation on exposure of P(SiMe3)3 to a variety of protic reagents including water, methanol, and carboxylic acid, corroborating observations of P(SiMe3)3 speciation during the hot injection synthesis of InP QDs. Quantitative UV–vis comparisons between InP growth from P(SiMe3)3 and HP(SiMe3)2 show unambiguously that when total H+-content is accounted for, particle size, size dispersity, and concentration are indistinguishable for these two reagents. The dual role of myristic acid in P–Si bond cleavage and as a source of the myristate anion, an essential component of the quantum dot surface, is interrogated using tetrabutylammonium myristate, confirming that it is the protons that are responsible for increased quantum dot polydispersity. Together these data support the existence of a competing acid-catalyzed pathway in the conver...

Membrane Stress Caused by Octanoic acid in Saccharomyces cerevisiae

Abstract: In order to compete with petroleum-based fuel and chemicals, engineering a robust biocatalyst that can convert renewable feedstocks into biorenewable chemicals, such as carboxylic acids, is increasingly important. However, product toxicity is often problematic. In this study, the toxicity of the carboxylic acids hexanoic, octanoic, and decanoic acid on Saccharomyces cerevisiae was investigated, with a focus on octanoic acid. These compounds are completely inhibitory at concentrations of magnitude 1 mM, and the toxicity increases as chain length increases and as media pH decreases. Transciptome analysis, reconstruction of gene regulatory network, and network component analysis suggested decreased membrane integrity during challenge with octanoic acid. This was confirmed by quantification of dose-dependent and chain length-dependent induction of membrane leakage, though membrane fluidity was not affected. This induction of membrane leakage could be significantly decreased by a period of pre-adaptation, and this pre-adaptation was accompanied by increased oleic acid content in the membrane, significantly increased production of saturated lipids relative to unsaturated lipids, and a significant increase in the average lipid chain length in the membrane. However, during adaptation cell surface hydrophobicity was not altered. The supplementation of oleic acid to the medium not only elevated the tolerance of yeast cells to octanoic acid but also attenuated the membrane leakiness. However, while attempts to mimic the oleic acid supplementation effects through expression of the Trichoplusia ni acyl-CoA Δ9 desaturase OLE1(TniNPVE desaturase) were able to increase the oleic acid content, the magnitude of the increase was not sufficient to reproduce the supplementation effect and increase octanoic acid tolerance. Similarly, introduction of cyclopropanated fatty acids through expression of the Escherichia coli cfa gene was not helpful for tolerance. Thus, we have provided quantitative evidence that carboxylic acids damage the yeast membrane and that manipulation of the lipid content of the membrane can increase tolerance, and possibly production, of these valuable products.

Direct Carboxylative Reactions for the Transformation of Carbon Dioxide into Carboxylic Acids and Derivatives

Abstract: Carbon dioxide is the ideal one-carbon source for organic synthesis because of its abundance, lack of toxicity, and potential as a renewable resource, but is limited by its high stability and low reactivity. The carboxylation of carbon nucleophiles with carbon dioxide to form new carbon–carbon bonds is therefore an attractive method for the synthesis of carboxylic acids and derivatives, which are in turn valuable organic products. Thus, the designing of mild methods to catalytically activate carbon dioxide and form carbon–carbon bonds is a challenge that is of both academic and practical importance. This review is focused on the direct carboxylative reaction for the transformation of carbon dioxide into carboxylic acids and derivatives from the carboxylation of carbon nucleophiles, reductive hydrocarboxylation of unsaturated compounds, carboxylation via oxidative cycloaddition, carboxylation of carbon–hydrogen bonds, and electrochemical carboxylation. 1 Introduction 2 Carboxylation of Carbon Nucleophiles 2.1 Carboxylation of Organotin Reagents 2.2 Carboxylation of Organoboron Reagents 2.3 Carboxylation of Organozinc Reagents 2.4 Carboxylation of Other Nucleophiles 3 Reductive Hydrocarboxylation of Unsaturated Compounds 4 Carboxylation via Oxidative Cycloaddition 5 Carboxylation of Carbon–Hydrogen Bonds 5.1 Carboxylation of Terminal Alkynes 5.2 Carboxylation of sp2 Carbon–Hydrogen Bonds 5.3 Carboxylation of sp3 Carbon–Hydrogen Bonds 6 Electrochemical Carboxylation 7 Conclusion

2-Hydrazinoquinoline as a derivatization agent for LC-MS-based metabolomic investigation of diabetic ketoacidosis.

Abstract: Short-chain carboxylic acids, aldehydes and ketones are products and regulators of many important metabolic pathways. Their levels in biofluids and tissues reflect the status of specific metabolic reactions, the homeostasis of the whole metabolic system and the wellbeing of a biological entity. In this study, the use of 2-hydrazinoquinoline (HQ) as a novel derivatization agent was explored and optimized for simultaneous liquid chromatography-mass spectrometry (LC-MS) analysis of carboxylic acids, aldehydes and ketones in biological samples. The formation of carboxylic acid derivative is attributed to the esterification reaction between HQ and a carboxyl group, while the production of aldehyde and ketone derivatives is through the formation of Schiff bases between HQ and a carbonyl group. The compatibility of HQ with biological samples was demonstrated by derivatizing urine, serum and liver extract samples. Using this HQ-based approach, the kinetics of type 1 diabetes-induced metabolic changes was characterized by the LC-MS-based metabolomic analysis of urine samples from streptozotocin (STZ)-treated mice. Subsequently, carboxylic acid, aldehyde and ketone metabolites associated with STZ-elicited disruption of nutrient and energy metabolism were conveniently identified and elucidated. Overall, HQ derivatization of carboxylic acids, aldehydes and ketones could serve as a useful tool for the LC-MS-based metabolomic investigation of endogenous metabolism.

Polymorphic Co-crystals from Polymorphic Co-crystal Formers: Competition between Carboxylic Acid···Pyridine and Phenol···Pyridine Hydrogen Bonds

Abstract: The recent literature has shown an increase in the number of co-crystals reported to be polymorphic, with at least 45 such systems identified thus far. The question of whether co-crystals, defined as any multicomponent neutral molecular complex that forms a crystalline solid, are inherently less prone to polymorphism than the individual components is shown to be untrue in four sets of polymorphic co-crystals. The co-crystal formers in this study, acridine, nicotinamide, 3-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, malonic acid, and pimelic acid, are all polymorphic in their unimolecular states and are shown to be dimorphic in the following combinations: (3-hydroxybenzoic acid)·(acridine) [1(I) and 1(II)], (2,4-dihydroxybenzoic acid)·(nicotinamide) [4(I) and 4(II)], (malonic acid)·(nicotinamide) [5(I) and 5(II)], and (pimelic acid)·(nicotinamide) [6(I) and 6(II)]. These co-crystals are assembled primarily using carboxylic acid and phenol hydrogen bond donors that hydrogen bond to pyridine N or amide c...

Aqueous Phase Hydrogenation of Acetic Acid and Its Promotional Effect on p-Cresol Hydrodeoxygenation

Abstract: A systematic study of the comparative performances of various supported noble metal catalysts for the aqueous phase hydrogenation of acetic acid (as a model carboxylic acid in bio-oils) by itself and in combination with p-cresol (as a model phenolic compound in bio-oils) is presented. It was found that Ru/C catalyst shows the highest activity for acetic acid hydrogenation among the tested catalysts, followed by Ru/Al2O3, Pt/C, Pt/Al2O3, Pd/Al2O3, and Pd/C. CH4 and CO2 were observed to be the major products on all of these catalysts at typical hydroprocessing temperatures (∼300 °C). A systematic study on parametric effects with the Ru/C catalyst shows that the product distribution is dependent upon the temperature and presence of water. At low temperatures (∼150 °C), acetic acid hydrogenation is favored with higher selectivity to ethanol, while at high temperatures (∼300 °C), acetic acid decomposition and ethanol reforming/hydrogenolysis dominate with CO2 and CH4 as the major products. When water is replac...

Inhibition of the β-class carbonic anhydrases from Mycobacterium tuberculosis with carboxylic acids

Abstract: The growth of Mycobacterium tuberculosis is strongly inhibited by weak acids although the mechanism by which these compounds act is not completely understood. A series of substituted benzoic acids, nipecotic acid, ortho- and para-coumaric acid, caffeic acid and ferulic acid were investigated as inhibitors of three β-class carbonic anhydrases (CAs, EC 4.2.1.1) from this pathogen, mtCA 1 (Rv1284), mtCA 2 (Rv3588c) and mtCA 3 (Rv3273). All three enzymes were inhibited with efficacies between the submicromolar to the micromolar one, depending on the scaffold present in the carboxylic acid. mtCA 3 was the isoform mostly inhibited by these compounds (KIs in the range of 0.11–0.97 µM); followed by mtCA 2 (KIs in the range of 0.59–8.10 µM), whereas against mtCA 1, these carboxylic acids showed inhibition constants in the range of 2.25–7.13 µM. This class of relatively underexplored β-CA inhibitors warrant further in vivo studies, as they may have the potential for developing antimycobacterial agents with a divers...