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Science Advances Jul 2019The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was...
The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing-enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.
Topics: Boronic Acids; Cyanides; Mass Spectrometry; Microwaves; Molecular Structure; Small Molecule Libraries
PubMed: 31281893
DOI: 10.1126/sciadv.aaw4607 -
American Journal of Physiology. Renal... Nov 2003The sources and rates of metabolic acid production in relation to renal net acid excretion and thus acid balance in humans have remained controversial. The techniques... (Review)
Review
The sources and rates of metabolic acid production in relation to renal net acid excretion and thus acid balance in humans have remained controversial. The techniques and possible errors in these measurements are reviewed, as is the relationship of charge balance to acid balance. The results demonstrate that when acid production is experimentally increased among healthy subjects, renal net acid excretion does not increase as much as acid production so that acid balances become positive. These positive imbalances are accompanied by equivalently negative charge balances that are the result of bone buffering of retained H+ and loss of bone Ca2+ into the urine. The data also demonstrate that when acid production is experimentally reduced during the administration of KHCO3, renal net acid excretion does not decrease as much as the decrease in acid production so that acid balances become negative, or, in opposite terms, there are equivalently positive HCO3- balances. Equivalently positive K+ and Ca2+ balances, and thus positive charge balances, accompany these negative acid imbalances. Similarly, positive Na+ balances, and thus positive charge balances, accompany these negative acid balances during the administration of NaHCO3. These charge balances are likely the result of the adsorption of HCO3- onto the crystal surfaces of bone mineral. There do not appear to be significant errors in the measurements.
Topics: Acid-Base Equilibrium; Acidosis; Acids; Bone and Bones; Buffers; Calcium; Chronic Disease; Electrochemistry; Humans; Kidney Diseases; Reference Values
PubMed: 14532161
DOI: 10.1152/ajprenal.00115.2003 -
Molecules (Basel, Switzerland) Feb 2019Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products,... (Review)
Review
Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products, nucleic acids, and as chemical modification in protein and peptides, phosphorous can form P⁻N (phosphoramidate), P⁻S (phosphorothioate), and P⁻C (e.g., phosphonate and phosphinate) linkages. While rare, these moieties play critical roles in many processes and in all forms of life. In this review we thoroughly categorize P⁻N, P⁻S, and P⁻C natural organophosphorus compounds. Information on biological source, biological activity, and biosynthesis is included, if known. This review also summarizes the role of phosphorylation on unusual amino acids in proteins (- and -phosphorylation) and reviews the natural phosphorothioate (P⁻S) and phosphoramidate (P⁻N) modifications of DNA and nucleotides with an emphasis on their role in the metabolism of the cell. We challenge the commonly held notion that nonphosphate organophosphorus functional groups are an oddity of biochemistry, with no central role in the metabolism of the cell. We postulate that the extent of utilization of some phosphorus groups by life, especially those containing P⁻N bonds, is likely severely underestimated and has been largely overlooked, mainly due to the technological limitations in their detection and analysis.
Topics: Amides; Biological Products; Organophosphonates; Organophosphorus Compounds; Phosphates; Phosphoric Acids
PubMed: 30823503
DOI: 10.3390/molecules24050866 -
Brazilian Journal of Microbiology :... Dec 2013Microbiologically induced deterioration (MID) causes corrosion of concrete by producing acids (including organic and inorganic acids) that degrade concrete components... (Review)
Review
Microbiologically induced deterioration (MID) causes corrosion of concrete by producing acids (including organic and inorganic acids) that degrade concrete components and thus compromise the integrity of sewer pipelines and other structures, creating significant problems worldwide. Understanding of the fundamental corrosion process and the causal agents will help us develop an appropriate strategy to minimize the costs in repairs. This review presents how microorganisms induce the deterioration of concrete, including the organisms involved and their colonization and succession on concrete, the microbial deterioration mechanism, the approaches of studying MID and safeguards against concrete biodeterioration. In addition, the uninvestigated research area of MID is also proposed.
Topics: Acids; Construction Materials; Corrosion; Environmental Microbiology
PubMed: 24688488
DOI: 10.1590/S1517-83822014005000006 -
BMC Microbiology Feb 2021In caries, low pH drives selection and enrichment of acidogenic and aciduric bacteria in oral biofilms, and development of acid tolerance in early colonizers is thought...
BACKGROUND
In caries, low pH drives selection and enrichment of acidogenic and aciduric bacteria in oral biofilms, and development of acid tolerance in early colonizers is thought to play a key role in this shift. Since previous studies have focussed on planktonic cells, the effect of biofilm growth as well as the role of a salivary pellicle on this process is largely unknown. We explored acid tolerance and acid tolerance response (ATR) induction in biofilm cells of both clinical and laboratory strains of three oral streptococcal species (Streptococcus gordonii, Streptococcus oralis and Streptococcus mutans) as well as two oral species of Actinomyces (A. naeslundii and A. odontolyticus) and examined the role of salivary proteins in acid tolerance development.
METHODS
Biofilms were formed on surfaces in Ibidi® mini flow cells with or without a coating of salivary proteins and acid tolerance assessed by exposing them to a challenge known to kill non-acid tolerant cells (pH 3.5 for 30 min) followed by staining with LIVE/DEAD BacLight and confocal scanning laser microscopy. The ability to induce an ATR was assessed by exposing the biofilms to an adaptation pH (pH 5.5) for 2 hours prior to the low pH challenge.
RESULTS
Biofilm formation significantly increased acid tolerance in all the clinical streptococcal strains (P < 0.05) whereas the laboratory strains varied in their response. In biofilms, S. oralis was much more acid tolerant than S. gordonii or S. mutans. A. naeslundii showed a significant increase in acid tolerance in biofilms compared to planktonic cells (P < 0.001) which was not seen for A. odontolyticus. All strains except S. oralis induced an ATR after pre-exposure to pH 5.5 (P < 0.05). The presence of a salivary pellicle enhanced both acid tolerance development and ATR induction in S. gordonii biofilms (P < 0.05) but did not affect the other bacteria to the same extent.
CONCLUSIONS
These findings suggest that factors such as surface contact, the presence of a salivary pellicle and sensing of environmental pH can contribute to the development of high levels of acid tolerance amongst early colonizers in oral biofilms which may be important in the initiation of caries.
Topics: Acids; Adaptation, Physiological; Biofilms; Humans; Hydrogen-Ion Concentration; Mouth; Salivary Proteins and Peptides; Streptococcal Infections; Streptococcus
PubMed: 33583397
DOI: 10.1186/s12866-021-02089-2 -
Journal of Oleo Science Sep 2022Green tea is a popular refreshing drink with several functional properties attributed to its bioactive compounds. The bioactive content and composition vary with several...
Green tea is a popular refreshing drink with several functional properties attributed to its bioactive compounds. The bioactive content and composition vary with several factors. Several advances in chromatographic studies have facilitated the study of chemical composition of green tea leaves; however, the content of organic acids, particularly quinic acid, has not been explored fully. Therefore, changes in the content of organic acids, including quinic acid, in green tea leaves, were investigated in this study. All the studied varieties contained large amounts of quinic and oxalic acids. Kukicha and Matcha contained the highest and lowest amounts of quinic acid, respectively. Furthermore, high-grade Matcha had a significantly lower quinic acid content than low-grade Matcha. The Asatsuyu sample had the lowest quinic acid content in 2018 and 2019 compared with the other green tea varieties. The content of quinic acid increased with maturity, but that of oxalic, malic, succinic, and citric acids decreased after a slight increase. Shading cultivation in Saeakari significantly lowered the quinic acid content and slightly increased the content of malic, citric, and oxalic acids. Malic acid and citric acid content in Yabukita changed with sunrise and sunset, but that of other organic acids did not show any considerable change. These results show that using an appropriate plucking time could lead to further improvement in the quality of green tea leaves. Overall, green tea is a good source of quinic acid, which will attract attention in future functional research on this drink.
Topics: Acids; Chromatography, High Pressure Liquid; Citric Acid; Oxalates; Plant Extracts; Plant Leaves; Quinic Acid; Tea
PubMed: 35965093
DOI: 10.5650/jos.ess22135 -
Chemical Reviews Dec 2021Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily... (Review)
Review
Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily available starting materials. Despite their great potential, catalytic enantioselective additions of alcohols across a C-C multiple bond are particularly underdeveloped, especially compared to other hydrofunctionalization methods such as hydroamination. However, driven by some recent innovations, e.g., asymmetric MHAT methods, asymmetric photocatalytic methods, and the development of extremely strong chiral Brønsted acids, there has been a gratifying surge of reports in this burgeoning field. The goal of this review is to survey the growing landscape of asymmetric hydroalkoxylation by highlighting exciting new advances, deconstructing mechanistic underpinnings, and drawing insight from related asymmetric hydroacyloxylation and hydration. A deep appreciation of the underlying principles informs an understanding of the various selectivity parameters and activation modes in the realm of asymmetric alkene hydrofunctionalization while simultaneously evoking the outstanding challenges to the field moving forward. Overall, we aim to lay a foundation for cross-fertilization among various catalytic fields and spur further innovation in asymmetric hydroalkoxylations of C-C multiple bonds.
Topics: Acids; Alkenes; Catalysis; Oxidation-Reduction; Stereoisomerism
PubMed: 34860509
DOI: 10.1021/acs.chemrev.1c00620 -
ChemMedChem Mar 2013The carboxylic acid functional group can be an important constituent of a pharmacophore, however, the presence of this moiety can also be responsible for significant... (Review)
Review
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.
Topics: Azoles; Carboxylic Acids; Drug Design; Furans; Hydroxamic Acids; Ketones; Kinetics; Phosphorous Acids; Sulfonamides; Sulfonic Acids
PubMed: 23361977
DOI: 10.1002/cmdc.201200585 -
Omics : a Journal of Integrative Biology Oct 2010Weak acids are widely used as food preservatives (e.g., acetic, propionic, benzoic, and sorbic acids), herbicides (e.g., 2,4-dichlorophenoxyacetic acid), and as... (Review)
Review
Weak acids are widely used as food preservatives (e.g., acetic, propionic, benzoic, and sorbic acids), herbicides (e.g., 2,4-dichlorophenoxyacetic acid), and as antimalarial (e.g., artesunic and artemisinic acids), anticancer (e.g., artesunic acid), and immunosuppressive (e.g., mycophenolic acid) drugs, among other possible applications. The understanding of the mechanisms underlying the adaptive response and resistance to these weak acids is a prerequisite to develop more effective strategies to control spoilage yeasts, and the emergence of resistant weeds, drug resistant parasites or cancer cells. Furthermore, the identification of toxicity mechanisms and resistance determinants to weak acid-based pharmaceuticals increases current knowledge on their cytotoxic effects and may lead to the identification of new drug targets. This review integrates current knowledge on the mechanisms of toxicity and tolerance to weak acid stress obtained in the model eukaryote Saccharomyces cerevisiae using genome-wide approaches and more detailed gene-by-gene analysis. The major features of the yeast response to weak acids in general, and the more specific responses and resistance mechanisms towards a specific weak acid or a group of weak acids, depending on the chemical nature of the side chain R group (R-COOH), are highlighted. The involvement of several transcriptional regulatory networks in the genomic response to different weak acids is discussed, focusing on the regulatory pathways controlled by the transcription factors Msn2p/Msn4p, War1p, Haa1p, Rim101p, and Pdr1p/Pdr3p, which are known to orchestrate weak acid stress response in yeast. The extrapolation of the knowledge gathered in yeast to other eukaryotes is also attempted.
Topics: Acids; Adaptation, Biological; Cell Membrane; Gene Expression Regulation, Fungal; Genome, Fungal; Molecular Structure; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Transcription, Genetic
PubMed: 20955006
DOI: 10.1089/omi.2010.0072 -
Helicobacter Aug 2017Helicobacter pylori is well adapted to colonize the epithelial surface of the human gastric mucosa and can cause persistent infections. In order to infect the gastric... (Review)
Review
BACKGROUND
Helicobacter pylori is well adapted to colonize the epithelial surface of the human gastric mucosa and can cause persistent infections. In order to infect the gastric mucosa, it has to survive in the gastric acidic pH. This organism has well developed mechanisms to neutralize the effects of acidic pH.
OBJECTIVE
This review article was designed to summarize the various functional and molecular aspects by which the bacterium can combat and survive the gastric acidic pH in order to establish the persistent infections.
METHODS
We used the keywords (acid acclimation, gastric acidic environment, H. pylori and survival) in combination or alone for pubmed search of recent scientific literatures. One hundred and forty one papers published between 1989 and 2016 were sorted out. The articles published with only abstracts, other than in English language, case reports and reviews were excluded.
RESULTS
Many literatures describing the role of several factors in acid survival were found. Recently, the role of several other factors has been claimed to participate in acid survival.
CONCLUSION
In conclusion, this organism has well characterized mechanisms for acid survival.
Topics: Acids; Adaptation, Physiological; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Microbial Viability; Stress, Physiological
PubMed: 28402047
DOI: 10.1111/hel.12386