Enantiomer separation of 2-halomandelic acids via diastereomeric salt formation with chiral N-substituted 2-amino-2-phenylethanols.

Chiral N-substituted secondary 1,2-aminoalcohols have been developed for the enantioseparation of ortho-halomandelic acids (o-X-MAs) via diastereomeric salt formation. Two structural isomers, N-methyl-2-amino-1,2-diphenylethanol and N-benzyl-2-amino-2-phenylethanol, showed high separation abilities for o-X-MAs (X = Cl, Br, I). The chiral recognition mechanism was elucidated by crystallographic analysis of the less-soluble salts. The substituents on the nitrogen atom of the resolving agents and the inclusion of the crystallization solvent stabilized the salt and enhanced their separation ability.

Novel ethylenediamine-ß-cyclodextrin grafted membranes for the chiral separation of mandelic acid and its derivatives.

In the present study, flat cellulose acetate ultrafiltration membranes were prepared first by nonsolvent induced phase separation method. Then chiral membranes for separating the enantiomers were prepared by grafting the ultrafiltration membranes using ethylenediamine-ß-cyclodextrin as the chiral selector and epichlorohydrin as the spacer arm. The pure water permeability of the ultrafiltration membrane was around 115 L·m-2·h-1·bar-1. The properties of the chiral membranes were characterized using infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The chiral membrane performance in enantiomer separation was evaluated with racemates, such as mandelic acid (MA), 2-chloromandelic acid (2-ClMA), 4-chloromandelic acid (4-ClMA), and methyl mandelate (MM). The influence of feed concentration on the separation efficiency was also investigated. The results indicated that the enantiomeric excess percentages (e.e%) of the racemic mixtures for these four chiral compounds were up to 31.8%, 25.4%, 17.8%, and 32.6%, respectively. The binding free energy of the chiral selector with the (S)-enantiomer calculated by molecular dynamics simulations was stronger than that with the (R)-enantiomer, which was consistent with the experimental results (higher concentration of (R)-enantiomer in the permeate). This supports the affinity absorption-separation mechanism.

Enhancement of Exfoliating Effects through the Novel Cosmetic Ingredient Mandelic acid_Carnitine Ion-Pairing Complex.

PURPOSE: This study aimed to develop a novel exfoliating material with high efficacy and low irritation by synthesizing the Mandelic acid_Carnitine ion pairing complex (M_C complex) and evaluating its exfoliating properties. Additionally, the study assessed the skin improvement effects of the M_C complex through clinical evaluations. METHODS: The M_C complex was synthesized in a 1:1 molar ratio of Mandelic acid and Carnitine. Structural characterization was performed using dynamic light scattering and Fourier-transform infrared spectroscopy. Exfoliating efficacy was evaluated on porcine skin, and clinical assessments were conducted on human subjects to measure various skin improvement parameters. RESULTS: The formation of the M_C complex was confirmed through particle size analysis, zeta-potential measurements, and FT-IR spectroscopy. The M_C complex demonstrated superior exfoliating efficacy compared to Mandelic acid alone, especially at pH 4.5. Clinical evaluations showed significant improvements in blackheads, whiteheads, pore volume, depth, density, count, and affected area, as well as skin texture. No adverse reactions were observed. CONCLUSION: The M_C complex exhibits high exfoliating efficacy and minimal irritation, making it a promising cosmetic ingredient for improving skin health. These findings support its potential as a low-irritation exfoliating material under mildly acidic conditions, contributing to overall skin health enhancement.

Formulating Sustainable Emulsions: Mandelic Acid and Essential Oils as Natural Preservatives.

Emulsion products with natural antimicrobials are becoming increasingly popular for topical application. Mandelic Acid is interesting in cosmetics due to its potent exfoliating properties, which have driven advancements in skincare technologies. Essential oils have various properties, of which the most useful in cosmetics are those that do not cause irritation, smell pleasant, and have other beneficial properties such as antimicrobial effects. Emulsions with Mandelic Acid and essential oils from Satureja montana, Lemongrass, and Litsea cubeba were formulated and microbiologically tested for their preservative effectiveness. The effect of the treatments on skin condition was monitored by non-invasive diagnostic methods, such as hydration, transepidermal water loss, and pH value. Sensory analysis revealed that the matrix containing Mandelic Acid alone or combined with Litsea Cubeba Oil was the best-performing formulation, consistent with the compliant results of antimicrobial efficacy. The topical form of this cosmetic product has demonstrated excellent preservative activity and desirable biophysical efficacy on the skin.

Structural Characterization and Bioactivity of a Titanium(IV)-Oxo Complex Stabilized by Mandelate Ligands.

Research on titanium-oxo complexes (TOCs) is usually focused on their structure and photocatalytic properties. Findings from these investigations further sparked our interest in exploring their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the evaluation of the antimicrobial activity of the obtained materials. The investigations performed demonstrated the antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, which is also may be use for producing composite coatings.

Green synthesis aspects of (R)-(-)-mandelic acid; a potent pharmaceutically active agent and its future prospects.

(R)-(-)-mandelic acid is an important carboxylic acid known for its numerous potential applications in the pharmaceutical industry as it is an ideal starting material for the synthesis of antibiotics, antiobesity drugs and antitumor agents. In past few decades, the synthesis of (R)-(-)-mandelic acid has been undertaken mainly through the chemical route. However, chemical synthesis of optically pure (R)-(-)-mandelic acid is difficult to achieve at an industrial scale. Therefore, its microbe mediated production has gained considerable attention as it exhibits many merits over the chemical approaches. The present review focuses on various biotechnological strategies for the production of (R)-(-)-mandelic acid through microbial biotransformation and enzymatic catalysis; in particular, an analysis and comparison of the synthetic methods and different enzymes. The wild type as well as recombinant microbial strains for the production of (R)-(-)-mandelic acid have been elucidated. In addition, different microbial strategies used for maximum bioconversion of mandelonitrile into (R)-(-)-mandelic acid are discussed in detail with regard to higher substrate tolerance and maximum bioconversion.HighlightsMandelonitrile, mandelamide and o-chloromandelonitrile can be used as substrates to produce (R)-(-)-mandelic acid by enzymes.Three enzymes (nitrilase, nitrile hydratase and amidase) are systematically introduced for production of (R)-(-)-mandelic acid.Microbial transformation is able to produce optically pure (R)-(-)-mandelic acid with 100% productive yield.

Enantioseparation of amino acid and mandelic acid enantiomers using Josiphos-metal complexes as chiral extractants.

The development of new and efficient chiral extractants has always been the research hotspot and difficulty in the field of chiral extraction. Josiphos, a famous ferrocene derivative catalyst, is employed as a chiral extractant in enantioseparation of amino acid and mandelic acid enantiomers. The influences of metal ions, organic solvents, pH of the aqueous solution, extractant concentrations, and extraction temperature on enantioselectivities are systematically studied. The result reveals that Josiphos-Pd has good capabilities to enantioseparate 4-nitro-phenylalanine (Nphe), 3-chloro-phenylglycine (Cpheg), and mandelic acid (MA) with separation factors (α) of 3.30, 2.65, and 2.18, respectively. The pH of the aqueous phase and Josiphos-Pd concentration affect the extraction significantly, whereas extraction temperature shows little influence. After optimizing by response surface method, the mathematical models for extractions are established. And the highest experimental performance factors (pf) for Nphe, Cpheg, and MA are 0.1843, 0.1335, and 0.08884, respectively.

Structure-Chiral Selectivity Relationships of Various Mandelic Acid Derivatives on Octakis 2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin Containing Gas Chromatographic Stationary.

Frequently, a good chiral separation is the result of long trial and error processes. The three-point interaction mechanisms require the fair geometrical fitting and functional group compatibility of the interacting groups. Structure-chiral selectivity correlations are guidelines that can be established via trough systematic studies using model compounds. The enantiorecognition of the test compounds was studied on an octakis 2,3-Di-O-acetyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin (TBDMSDAGCD) chiral selector. In our work, mandelic acid and its variously substituted compounds were used as model compounds to establish adaptable rules for other enantiomeric pairs. The mandelic acid and its modified compounds were altered at both their carboxyl and hydroxyl positions to test the key interaction forces of the chiral recognition processes. Ring- and alkyl-substituted mandelic acid derivatives were also used in our experiments. The chiral selectivity values of 20 test compounds were measured and extrapolated to 100 °C. The hydrogen donor abilities of test compounds improved their chiral selectivities. The inclusion phenomenon also played a role in chiral recognition processes in several cases. Enantiomer elution reversals were observed for different derivatives of hydroxyl groups, providing evidence for the multimodal character of the selector. The results of our research can serve as guidelines to achieve appropriate chiral separation for other enantiomeric pairs.

Research on the Electron Structure and Antimicrobial Properties of Mandelic Acid and Its Alkali Metal Salts.

This article investigated the structure, and the spectroscopic and antimicrobial properties of mandelic acid and its alkali metal salts. The electron charge distribution and aromaticity in the analyzed molecules were investigated using molecular spectroscopy methods (FT-IR, FT-Raman, 1H NMR, and 13C NMR) and theoretical calculations (structure, NBO, HOMO, LUMO, energy descriptors, and theoretical IR and NMR spectra). The B3LYP/6-311++G(d,p) method was used in the calculations. The antimicrobial activities of mandelic acid and its salt were tested against six bacteria: Gram-positive Listeria monocytogenes ATCC 13932, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and Loigolactobacillus backii KKP 3566; Gram-negative Escherichia coli ATCC 25922 and Salmonella Typhimurium ATCC 14028, as well as two yeast species, Rhodotorulla mucilaginosa KKP 3560 and Candida albicans ATCC 10231.

Non-Alcohol Hand Sanitiser Gels with Mandelic Acid and Essential Oils.

Antimicrobial hand gels have become extremely popular in recent years due to the COVID-19 pandemic. Frequent use of hand sanitising gel can lead to dryness and irritation of the skin. This work focuses on the preparation of antimicrobial acrylic acid (Carbomer)-based gels enhanced by non-traditional compounds-mandelic acid and essential oils-as a substitute for irritating ethanol. Physicochemical properties (pH and viscosity), stability and sensory attributes of the prepared gels were investigated. Antimicrobial activity against representative Gram-positive and Gram-negative bacteria and yeasts was determined. The prepared gels with mandelic acid and essential oil (cinnamon, clove, lemon, and thyme) proved to have antimicrobial activity and even better organoleptic properties than commercial ethanol-based antimicrobial gel. Further, results confirmed that the addition of mandelic acid had a desirable effect on gel properties (antimicrobial, consistency, stability). It has been shown that the essential oil/mandelic acid combination can be a dermatologically beneficial hand sanitiser compared to commercial products. Thus, the produced gels can be used as a natural alternative to alcohol-based daily hand hygiene sanitisers.

Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives.

Plant diseases caused by phytopathogenic fungi are a serious threat in the process of crop production and cause large economic losses to global agriculture. To obtain high-antifungal-activity compounds with novel action mechanisms, a series of 4-substituted mandelic acid derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. In vitro bioassay results revealed that some compounds exhibited excellent activity against the tested fungi. Among them, the EC50 values of E13 against Gibberella saubinetii (G. saubinetii), E6 against Verticillium dahlia (V. dahlia), and E18 against Sclerotinia sclerotiorum (S. sclerotiorum) were 20.4, 12.7, and 8.0 mg/L, respectively, which were highly superior to that of the commercialized fungicide mandipropamid. The morphological studies of G. saubinetii with a fluorescence microscope (FM) and scanning electron microscope (SEM) indicated that E13 broke the surface of the hyphae and destroyed cell membrane integrity with increased concentration, thereby inhibiting fungal reproduction. Further cytoplasmic content leakage determination results showed a dramatic increase of the nucleic acid and protein concentrations in mycelia with E13 treatment, which also indicated that the title compound E13 could destroy cell membrane integrity and affect the growth of fungi. These results provide important information for further study of the mechanism of action of mandelic acid derivatives and their structural derivatization.

[Determination of phenylglyoxylic acid and mandelic acid in urine by ultra high performance liquid chromatography tandem mass spectrometry].

Objective: To develop a method for the analysis of phenylglyoxylic acid (PGA) and mandelic acid (MA) in urine by ultra-high performance liquid chromatography tandem mass spectrometry. Methods: The study was conducted in April 2022. Urine samples were directly diluted with the initial mobile phase, separated by Waters HSS T3 column after passing through the membrane, and analyzed under negative ionization mode (ESI(-)) and multiple reaction monitoring (MRM) conditions, the contents of PGA and MA in human urine were quantitatively determined by external standard method. Results: The determination of PGA and MA showed a good linear relationship within the range of 10-1000 ng/ml, with a correlation coefficient of 0.9999. The linear regression equation of PGA was y=1141.4x+2157.3, the detection limit and lower limit of quantification of the method were 0.081 ng/ml and 0.269 ng/ml, and the recovery rate was 90.47%-99.83%. The linear regression equation of MA was y=62.8x+140.3, the detection limit and lower limit of quantification of the method were 0.551 ng/ml and 1.836 ng/ml, and the recovery rate was 92.75%-101.09%. The intra and inter batch precision of PGA and MA were both<5%. Conclusion: An ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of PGA and MA in urine was established.The sample pretreatment operation is simple, and the accuracy and precision of the method meet the standard requirements. It can be used for monitoring and evaluating PGA and MA in urine of the general population and occupational contact population.

Bacterial mandelic acid degradation pathway and its application in biotechnology.

Mandelic acid and its derivatives are an important class of chemical synthetic blocks, which is widely used in drug synthesis and stereochemistry research. In nature, mandelic acid degradation pathway has been widely identified and analysed as a representative pathway of aromatic compounds degradation. The most studied mandelic acid degradation pathway from Pseudomonas putida consists of mandelate racemase, S-mandelate dehydrogenase, benzoylformate decarboxylase, benzaldehyde dehydrogenase and downstream benzoic acid degradation pathways. Because of the ability to catalyse various reactions of aromatic substrates, pathway enzymes have been widely used in biocatalysis, kinetic resolution, chiral compounds synthesis or construction of new metabolic pathways. In this paper, the physiological significance and the existing range of the mandelic acid degradation pathway were introduced first. Then each of the enzymes in the pathway is reviewed one by one, including the researches on enzymatic properties and the applications in biotechnology as well as efforts that have been made to modify the substrate specificity or improving catalytic activity by enzyme engineering to adapt different applications. The composition of the important metabolic pathway of bacterial mandelic acid degradation pathway as well as the researches and applications of pathway enzymes is summarized in this review for the first time.

Mandelic acid-based spirothiazolidinones targeting M. tuberculosis: Synthesis, in vitro and in silico investigations.

A series of new spirothiazolidinone derivatives with a mandelic acid moiety were synthesized and subsequently tested in growth inhibition assays against Mycobacterium tuberculosis strain H37Rv. Compound 16 displayed the highest inhibition value of 98% at lower than 6.25 µg/mL concentration. A single crystal X-ray analysis was conducted on this compound to confirm the structure and determine its absolute configuration. Afterwards, reverse docking and molecular dynamics simulations of this specific stereoisomer were performed against a selection of 10 putative targets of M. tuberculosis to suggest possible mechanisms of action. Our results suggest HadAB, Pks13, DprE1, FadD32 and InhA as possible target proteins for the observed antimycobacterial activity of compound 16.

The study of biological activity of mandelic acid and its alkali metal salts in wastewaters.

In the present work we compared the biological activity of mandelic acid (MA) and its Li, Na, K, Rb and Cs salts. The study also investigated the effect of raw wastewaters (RW) and treated wastewaters (TW), comparable to microbial medium (MM) on the biological activity of the tested chemical compounds used in concentrations of 5; 2.5; 1.25; 0.625; 0.3125 mg/ml. In the present experiment the evaluation of the following parameters was performed: E. coli (ATCC 25922) cells viability, growth inhibition of E. coli (ATCC 25922), the inhibition of GFP protein, genotoxicity and ROS generation. Our results showed that three main factors differentiated the antibacterial activity of MA and its Li, Na, K, Rb and Cs salts: study environment (MM, RW, TW), metal forming salt of mandelic acid and concentration of tested compounds. Additionally, raw and treated wastewater, compared to microbial medium, changes the antimicrobial activity of MA and its salts in relation to the E. coli strain. We also detected that both MA and its salts affect the GFP protein and the induction of the recA promoter (genotoxicity test). The activity of the tested salts in relation to these two parameters is strictly dependent on the type of salt-forming metal and the concentration used. The analysis of ROS synthesis suggests that in the majority of the studied mandelic acid salts, oxidative stress is the dominant mechanism of cytotoxicity and genotoxicity. We also showed that both raw wastewaters (RW) and treated wastewaters (TW), compared to microbial medium (MM), change significantly the activity of MA and its salts.

Constitutive secretory expression and characterization of nitrilase from Alcaligenes faecalis in Pichia pastoris for production of R-mandelic acid.

Nitrilases can directly hydrolyze nitrile compounds into carboxylic acids and ammonium. To solve the current problems of bioconversions using nitrilases, including the difficult separation of products from the resting cells used as the catalyst and high costs of chemical inducers, a nitrilase from Alcaligenes faecalis was heterologously expressed in Pichia pastoris X33. The stable nitrilase-expressing strain No.39-6-4 was obtained after three rounds of screening based on a combined detection method including dot-blot, SDS-PAGE, and western blot analyses, which confirmed the presence of recombinant nitrilase with a molecular mass of about 50 kDa. The temperature and pH optima of the nitrilase were 45°C and pH 7.5, respectively. Cu2+ , Zn2+ , and Tween 80 strongly inhibited the enzyme activity, but the optical purity of the product R-mandelic acid (R-MA) was stable, with practically 100% enantiomeric excess (ee). The nitrilase-producing P. pastoris strain developed in this study provides a basis for further research on the enzyme.

Enantioseparation of amino acid and mandelic acid enantiomers using Garphos derivatives as chiral extractants.

In this paper, Garphos with different substituents were employed as chiral extractants to enantioseparate racemic amino acid and mandelic acid. The influences of metal precursors, pH of aqueous solution, Garphos-metal concentration, extraction temperature, and substituent effect on extraction were investigated. The results indicated that the substituent groups significantly affected the π-π interaction between extractant and substrate. And the separation factors (α) for Garphos could be remarkably improved by regulating substituent groups. Garphos-II-Pd, Garphos-VI-Pd, Garphos-III-Pd, Garphos-I-Cu, Garphos-VI-Cu, and Garphos-V-Pd were the most efficient extractants for phenylalanine (Phe), homophenylalanine (Hphe), 4-nitrophenylalanine (Nphe), 3-chlorophenylglycine (Cpheg), mandelic acid (MA), and 2-chlormandelic acid (CMA) with α values of 2.40, 2.37, 5.37, 1.59, 5.98, and 3.69, respectively. This work provided an important reference for the design of efficient chiral extractants in future work.

A new chiral stationary phase based on noscapine: Synthesis, enantioseparation, and docking study.

Noscapine is an isolated compound from the opium poppy, with distinctive chiral structure and chemistry, interacts with other compounds due to having multiple π-acceptors, hydrogen bond acceptors, and ionic sites. Therefore, it has promising applicability for the enantioselective separation of a wide range of polar, acidic, basic, and neutral compounds. A new noscapine derivative chiral stationary phase (ND-CSP) has been synthesized by consecutive N-demethylation, reduction, and N-propargylation of noscapine followed by attachment of a solid epoxy-functionalized silica bed through the 1,3-dipolar Huisgen cycloaddition. The noscapine derivative-based stationary phase provides a considerable surface coverage, which is greater than some commercial CSPs and can validate better enantioresolution performance. The major advantages inherent to this chiral selector are stability, reproducibility after more than 200 tests, and substantial loading capacity. The characterization by Fourier transform infrared (FTIR) spectroscopy and elemental analysis indicated successful functionalization of the silica surface. Chromatographic method conditions like flow rate and mobile phase composition for enantioseparation of various compounds such as warfarin, propranolol, mandelic acid, and a sulfanilamide derivative were optimized. Comparing the experimental results with docking data revealed a clear correlation between the calculated binding energy of ND-CSP and each enantiomer with the resolution of enantiomer peaks.

A review of extraction methods and analytical techniques for styrene and its metabolites in biological matrices.

We reviewed the toxicokinetics of styrene to introduce reliable surrogates for the biological monitoring of styrene workers. We have also discussed the extraction techniques and analytical methods of styrene and its metabolites. Sample preparation is the main bottleneck of the analytical techniques for styrene and its metabolites. Although some microextraction methods have been developed to overcome such disadvantages, some still have limitations such as long extraction time, fiber swelling and breakage, and the cost and the limited lifetime of the fiber. Among all, microextraction by packed sorbents, coupled with HPLC with ultraviolet detection (MEPS-HPLC-UV), can be the method of choice for determining styrene metabolites. Few studies investigated unchanged styrene in breath samples. Chemical determination of styrene in exhaled breath provides new insights into organ toxicity in workers with inhalation exposures and can be considered a fascinating tool in risk assessment strategies. Taking blood samples is invasive and less accepted by workers. In contrast, breath analysis is the most attractive method for workers because breath samples are easy to collect and non-invasive, and sample collection does not require the transfer of workers to health facilities. Therefore, developing selective and sensitive methods for determining styrene in breath samples is recommended for future studies.

Separation of Mandelic Acid by a Reactive Extraction Method Using Tertiary Amine in Different Organic Diluents.

Mandelic acid is a valuable chemical that is commonly used in the synthesis of various drugs, in antibacterial products, and as a skin care agent in cosmetics. As it is an important chemical, various methods are used to synthesize and extract this compound. However, the yields of the used processes is not significant. A dilute aqueous solution is obtained when using several production methods, such as a fermentation, etc. In this study, the reactive extraction of mandelic acid from aqueous solutions using tri-n-octylamine extractant at 298.15 K was investigated. Dimethyl phthalate (DMP), methyl isobutyl ketone (MIBK), 2-octanone, 1-octanol, n-pentane, octyl acetate, and toluene were used as diluents. The batch extraction results of the mandelic acid experiments were obtained for the development of a process design. Calculations of the loading factor (Z), distribution coefficient (D), and extraction efficiency (E%) were based on the experimental data. The highest separation yield was obtained as 98.13% for 0.458 mol.L-1 of tri-n-octylamine concentration in DMP. The overall extraction constants were analyzed for the complex of acid-amine by the Bizek approach, including K11, K12, and K23.