Asymmetric Reduction of C=N Bonds by Imine Reductases and Reductive Aminases
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Several enzymes exist which reduce a C=N bond during the reaction (Fig. 14.2). The focus of this chapter is on imine reductases suitable for apolar secondary amine synthesis (Fig 14.2A). Enzymes converting substrates that bear a carboxylic acid functional group will also be summarized (Fig. 14.2B). C=N-double bonds also occur in intermediates during the deamination of primary amines and amino acids: The enzymes amine dehydrogenases and amino acid dehydrogenases, which catalyze these deaminations (Fig. 14.2B), differ from IREDs as they are limited to the conversion/formation of primary amines, and thus are not discussed in this chapter. Differentiation of IREDs from other similar enzymes, which process an imine intermediate during their catalytic cycle.
Binders in Pharmaceutical Granulation
Dilip M. Parikh in Handbook of Pharmaceutical Granulation Technology, 2021
Low molecular weight aldehydes and carboxylic acids are found in many excipients including sugars, polymers, and unsaturated fats [18]. The most common reactive species of concern in solid dosage forms tend to be formaldehyde and its corresponding acid, formic acid. Table 4.3 lists typical levels of these impurities for various binders, granulation aids, and tableting excipients. Others include acetaldehyde, glyoxal, furfural, glyoxylic, and acetic acid. Carboxylic acids could be introduced because of not only carryover from manufacturing but also autoxidation of excipients, which, for example, leads to the formation of formaldehyde, which is then further oxidized to form formic acid. The presence of these impurities needs to be considered in acid-labile drugs as well as drugs with nucleophilic functional groups, for example, primary and secondary amines and hydroxyl groups [18,19]. Formaldehyde and formic acid have been identified as being of particular concern when using polysorbate, povidone, and polyethylene glycol [20,21].
Fats and Cardiovascular Disease
Stephen T. Sinatra, Mark C. Houston in Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
The three main ketones produced in the mitochondria are acetone, acetoacetic acid, and β-hydroxybutyric acid. (Figure 2.1) Acetone is a three-carbon ketone derived from sequential oxidation of longer chain FAs. Acetic acid is metabolized to acetone, but in very small amounts. Sometimes, it can be detected from the breath of people doing a very long fast. Acetoacetic acid is a true ketone but beta-hydroxybutyric acid is actually a small carboxylic acid but acts like a ketone for combustion. Kidneys usually make their own ketones as they require them for energy. The liver provides most of the other ketones for itself and the heart. The heart can process fatty acids to make its own energy, but when necessary, the liver will provide ketones for the heart and the rest of the body.20Ketone bodies.
Refining the structure−activity relationships of 2-phenylcyclopropane carboxylic acids as inhibitors of O-acetylserine sulfhydrylase isoforms
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Joana Magalhães, Nina Franko, Giannamaria Annunziato, Marco Pieroni, Roberto Benoni, Anna Nikitjuka, Andrea Mozzarelli, Stefano Bettati, Anna Karawajczyk, Aigars Jirgensons, Barbara Campanini, Gabriele Costantino
To investigate whether the carboxylic acid functionality might be modified, we replaced it with isosteric groups. Among the set of possible substituents, sulphonamides, a tetrazole ring and amides were initially investigated. While the sulphonamide group is a nonplanar isoster of the carboxylic acid, the tetrazole is planar and presents a similar acidity. On a similar vein, substituted amides were prepared because it is well known that the nature of the substituents might affect the selectivity of action toward different bacterial strains, either Gram-positive or Gram-negative29,30. For instance, in the case of sulphonamide drugs, potency and selectivity are modulated by the substituent at the amidic nitrogen31. Finally, we investigated the benzyl group attached at the C1 of the cyclopropane ring, with the aim to evaluate its substitution with heteroaromatic structures like pyridine and five-terms heteroaromatic rings, leading to molecules characterised by a lower lipophilicity.
Standardizing and increasing the utility of lipidomics: a look to the next decade
Published in Expert Review of Proteomics, 2020
Yuqin Wang, Eylan Yutuc, William J Griffiths
Simple fatty acids have been analyzed by GC-MS for decades [87] and were one of the first lipid classes to be analyzed by FAB-MS in the 1970’s [19,88]. For analysis by GC-MS the carboxylic acid group is usually converted to an ester. Many different types of fatty acyl esters have been generated for GC-MS analysis each with their own merits [23,85,89,90]. Besides the popular derivatization to methyl esters (fatty acyl methyl esters, FAME), two other derivatizations with particular merit are to picolinyl esters [23] and to pentafluorbenzyl esters [85]. Picolinyl esters fragment in the EI source through a charge-mediated mechanism to give a series of fragment-ions resulting from cleavage of successive carbon-carbon bonds, this allows the determination of the position of double bonds, cyclic groups and with trimethylsilylether derivatization of alcohol groups, the site of hydroxylations [23]. The advantage of derivatization to pentafluorobenzyl esters is that with negative chemical ionization dissociative electron capture occurs to give [RCO2]− ions allowing detection of chromatographically separated fatty acid derivatives at high sensitivity [85].
Carboxylic acids accelerate acidic environment-mediated nanoceria dissolution
Published in Nanotoxicology, 2019
Robert A. Yokel, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Alan K. Dozier, Uschi M. Graham
Phase 2 findings, 12 weeks after initiation of dialysis/dissolution, were characterized by lack of significant change in the superstructure from Phase 1, but obvious presence of nanoceria dissolution, resulting in rounding of nanoceria crystallite edges under all carboxylic acid conditions at pH 4.5. For example, in the presence of citric acid (Figure 6(w)) nanoceria agglomerates persisted into Phase 2, but the primary crystal particles bound to each other in the agglomerates changed due to dissolution. This was evidenced by the reduction of primary particle size, and to a lesser degree reduction of the agglomerate size, creating much larger voids between primary particles, that gave the agglomerates a skeletal appearance. This was observed for all ligands, with some variability among the ligands. Ligand type did not alter the crystallinity of the primary particles as they dissolved within the agglomerates but led to smaller and more rounded nanoceria. In general, the agglomerates did not collapse or reorganize as a result of the initial dissolution process. However, some carboxylic acids (malic and lactic) caused a much greater skeletal formation in the agglomerates, due to more rapid nanoceria dissolution. This resulted in significant void formation between primary nanoceria particles. This was observed to a lesser extent for other carboxylic acids (Figure 6). The reduction of primary particle size was associated with the increasing concentration of cerium in the bath (Figure 3).