Comparative Analysis of Efficacy of Lactic Acid 30% with Ferulic Peel 12% (Combination Peel) Versus TCA 10% with Ferulic Peel 12% (Combination Peel) for Photoageing Skin.

OBJECTIVES: Chemical peels are used to treat photoageing, pigmentation, improve complexion and dull skin, fine lines and scars. The objective of this study is to do comparative analysis of Lactic Acid 30% with Ferulic peel 12% (combination peel) versus TCA 10% with Ferulic peel 12% (combination peel) for Photoageing Skin. MATERIALS AND METHODS: This is a retrospective study from September 2021 to 2022 with total 50 female patients aged between 25 and 40 years were treated. Randomisation of patients was done (simple randomisation using lottery method) for both groups with 25 patients enrolled in each group. The first group (Group A-25 patients) were treated with lactic acid 30% with Ferulic peel 12% (combination peel). The second group (Group B-25 patients) were treated with TCA 10% with Ferulic peel 12% (combination peel). Inclusion and exclusion criteria have been defined for the study. Two scales have been used for assessing the results: Allergan Skin Roughness Scale (ASRS) and Allergan Fine Line Scale (AFLS). ASRS and AFLS scores were assessed at pre-treatment (pre) and post treatment (post-1 month after last peel session). Data were summarised in Mean ± SD (standard deviation). Pre and post groups were compared by paired t test. The pre to post change in outcome measures between two independent groups were compared by independent Student's t test. Discrete (categorical) groups were compared by Chi-square (χ2) test. A two-tailed (α=2) P < 0.05 was considered statistically significant. Analyses were performed on SPSS software (Windows version 22.0). Patients were followed up for 6 months post treatment. RESULTS: In Group A, comparing the pre and post ASRS score, paired t test showed significant (P < 0.001) decrease or improvement of 56.1%. In Group B, comparing the pre and post ASRS score, paired t test showed significant (P < 0.001) decrease or improvement of 52.8%. Comparing the pre to post mean decrease or improvement in ASRS score of two groups, Student's t test showed similar (P > 0.05) improvement between the two groups though it was 2.5% higher in Group B as compared to Group A. In Group A, comparing the pre and post AFLS score, paired t test showed significant (P < 0.001) decrease or improvement of 63.2% at post as compared to pre. In Group B, comparing the pre and post AFLS score, paired t test showed significant (P < 0.001) decrease or improvement of 58.8% at post as compared to pre. Further, comparing the pre to post mean decrease or improvement in AFLS score of two groups, Student's t test showed similar (P > 0.05) improvement between the two groups though it was 16.7% higher in Group A as compared to Group B. CONCLUSION: Study found both the treatments equally effective in the management of ageing skin after 6 months of treatment. However, study needs further validation on larger sample size, varied age groups and male gender. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Solid-state vibrational circular dichroism for pharmaceutical applications: Polymorphs and cocrystal of sofosbuvir.

X-ray diffraction is a commonly used technique in the pharmaceutical industry for the determination of the atomic and molecular structure of crystals. However, it is costly, sometimes time-consuming, and it requires a considerable degree of expertise. Vibrational circular dichroism (VCD) spectroscopy resolves these limitations, while also exhibiting substantial sensitivity to subtle modifications in the conformation and molecular packaging in the solid state. This study showcases VCD's ability to differentiate between various crystal structures of the same molecule (polymorphs, cocrystals). We examined the most effective approach for producing high-quality spectra and unveiled the intricate link between structure and spectrum via quantum-chemical computations. We rigorously assessed, using alanine as a model compound, multiple experimental conditions on the resulting VCD spectra, with the aim of proposing an optimal and efficient procedure. The proposed approach, which yields reliable, reproducible, and artifact-free results with maximal signal-to-noise ratio, was then validated using a set comprising of three amino acids (serine, alanine, tyrosine), one hydroxy acid (tartaric acid), and a monosaccharide (ribose) to mimic active pharmaceutical components. Finally, the optimized approach was applied to distinguish three polymorphs of the antiviral drug sofosbuvir and its cocrystal with piperazine. Our results indicate that solid-state VCD is a prompt, cost-effective, and easy-to-use technique to identify crystal structures, demonstrating potential for application in pharmaceuticals. We also adapted the cluster and transfer approach to calculate the spectral properties of molecules in a periodic crystal environment. Our findings demonstrate that this approach reliably produces solid-state VCD spectra of model compounds. Although for large molecules with many atoms per unit cell, such as sofosbuvir, this approach has to be simplified and provides only a qualitative match, spectral calculations, and energy analysis helped us to decipher the observed differences in the experimental spectra of sofosbuvir.

Fast, sensitive LC-MS resolution of α -hydroxy acid biomarkers via SPP-teicoplanin and an alternative UV detection approach.

Enantioseparation of α -hydroxy acids is essential since specific enantiomers of these compounds can be used as disease biomarkers for diagnosis and prognosis of cancer, brain diseases, kidney diseases, diabetes, etc., as well as in the food industry to ensure quality. HPLC methods were developed for the enantioselective separation of 11 α -hydroxy acids using a superficially porous particle-based teicoplanin (TeicoShell) chiral stationary phase. The retention behaviors observed for the hydroxy acids were HILIC, reversed phase, and ion-exclusion. While both mass spectrometry and UV spectroscopy detection methods could be used, specific mobile phases containing ammonium formate and potassium dihydrogen phosphate, respectively, were necessary with each approach. The LC-MS mode was approximately two orders of magnitude more sensitive than UV detection. Mobile phase acidity and ionic strength significantly affected enantioresolution and enantioselectivity. Interestingly, higher ionic strength resulted in increased retention and enantioresolution. It was noticed that for formate-containing mobile phases, using acetonitrile as the organic modifier usually resulted in greater enantioresolution compared to methanol. However, sometimes using acetonitrile with high ammonium formate concentrations led to lengthy retention times which could be avoided by using methanol as the organic modifier. Additionally, the enantiomeric purities of single enantiomer standards were determined and it was shown that almost all standards contained some levels of enantiomeric impurities.

Versatile capillary electrophoresis method for the direct chiral separation of aliphatic and aromatic α-hydroxy acids, ß-hydroxy acids and polyhydroxy acids using vancomycin as chiral selector.

Hydroxy acids (HAs) are ubiquitous in nature and play significant roles in various industrial and biological processes. Most HAs harbor at least one chiral center, therefore the development of efficient chiral analysis techniques for HA stereoisomers is of crucial importance across a wide range of fields. A capillary electrophoresis (CE) method was developed for the chiral analysis and quantification of aliphatic and aromatic α­hydroxy acid (AHA) enantiomers, aliphatic ß­hydroxy acid (BHA) enantiomers and aliphatic polyhydroxy acid (PHA) stereoisomers. Using a modified partial filling-counter current method with indirect UV detection, high resolution (Rs) was achieved with vancomycin as a chiral selector added to the background electrolyte composed of 10 mM of benzoic acid/L-histidine at pH 5 using a polyacrylamide-coated capillary. This method could be readily applied to the determination of the enantiomers of 12 aliphatic AHAs, 4 aromatic AHAs, 3 aliphatic BHAs, as well as to the determination of the stereoisomers of tartaric acid, 2,3-dihydroxybutanoic acid, 2,3,4,5-tetrahydroxypentanoic acid, and 2,3,4,5,6-pentahydroxyhexanoic acid without the need for sample derivatization. Finally, our study provides a robust and versatile strategy for the chiral and stereoselective analysis of a broad range of hydroxy acid compounds.

A pilot study examining a double-conjugated, retinoid-based skincare regimen for darker, blemish-prone skin.

BACKGROUND: Retinoids and alpha- and beta hydroxy acids are common components utilized in regimens for blemish-prone skin. However, balancing efficacy and tolerability is often challenging. PATIENTS/METHODS: This pilot study evaluated a double-conjugated retinoid serum specifically formulated for blemish-prone skin (AHARet-SA) in combination with exfoliating peel pads (double-conjugated retinoid, glycolic, lactic, and salicylic acids), a cleanser, mineral-based sunscreen, and a lightweight moisturizer in female participants with mild-to-moderate blemish-prone skin. Fifty-five percent of participants were Fitzpatrick Skin Type (FST) IV and 27% were FST V. Participants used the exfoliating peel pads (3x/week for 8 weeks; 2x/week for 4 weeks) followed by nightly AHARet-SA and a moisturizer (as needed). Improvements in skin were assessed using the 5-point Investigator Global Assessment Scale, and participant satisfaction and tolerability were assessed over 12 weeks. RESULTS: Significant mean improvement from baseline in skin clarity occurred after 4 weeks (14%; p = 0.04) with progressive improvements through week 12 (52%; p = 0.004). Eighty-eight percent of participants reported improvements in the appearance and texture of their skin and fewer blemishes/breakouts. Mild, transient adverse events were reported. CONCLUSIONS: A regimen comprised of a double-conjugated serum and exfoliating peel pads formulated for blemish-prone skin led to significant improvements from baseline in skin clarity after 12 weeks in participants with predominately darker skin tones and mild-to-moderate blemish-prone skin.

A Comprehensive Bibliographic Review Concerning the Efficacy of Organic Acids for Chemical Peels Treating Acne Vulgaris.

Acne vulgaris stands out as the most prevalent skin disorder among teenagers and young adults, causing physical discomfort and considerable economic and psychological burdens on individuals and society. A wide range of topical and systemic therapies are available in acne treatment. Chemical peeling is a skin resurfacing technique designed to rebuild healthy skin using exfoliating substances, a simple and affordable process with various dermatological uses. Chemical peels, classified as superficial, medium, and deep, have been utilized for acne vulgaris and multiple other skin issues. In these chemical peels, a diverse range of chemical substances is employed, each with its unique mode of action. Among these, α-hydroxy and ß-hydroxy acids have gathered attention for their efficacy in reducing acne lesions and enhancing overall skin appearance. Acids, such as salicylic acid, glycolic acid, or lactic acid, are commonly used in chemical peels due to their exfoliating and sebum-regulating properties. Despite the widespread use of these acids, there exists a lack of consensus regarding the most effective acid type and concentration for treating acne-prone skin. This review aims to bridge this knowledge gap by evaluating the effectiveness and safety of various organic acids used in chemical peels specifically for acne-prone skin. The findings of this comprehensive bibliographic review indicate that organic acid-based chemical peels represent effective and safe treatment options for individuals with acne-prone skin. Their adaptability sets these treatments apart; the choice of organic acid can be tailored to meet individual patient needs and tolerability levels. This personalized approach ensures that patients receive optimal care while minimizing the risks associated with the treatment. As research in this field progresses, it is anticipated that a more nuanced understanding of the ideal acid type and concentration will emerge, further enhancing the efficacy and safety of chemical peels for acne-prone skin.

HiSorb sorptive extraction for determining salivary short chain fatty acids and hydroxy acids in heart failure patients.

Variations in salivary short-chain fatty acids and hydroxy acids (e.g., lactic acid, and 3-hydroxybutyric acid) levels have been suggested to reflect the dysbiosis of human gut microbiota, which represents an additional factor involved in the onset of heart failure (HF) disease. The physical-chemical properties of these metabolites combined with the complex composition of biological matrices mean that sample pre-treatment procedures are almost unavoidable. This work describes a reliable, simple, and organic solvent free protocol for determining short-chain fatty acids and hydroxy acids in stimulated saliva samples collected from heart failure, obese, and hypertensive patients. The procedure is based on in-situ pentafluorobenzyl bromide (PFB-Br) derivatization and HiSorb sorptive extraction coupled to thermal desorption and gas chromatography-tandem mass spectrometry. The HiSorb extraction device is completely compatible with aqueous matrices, thus saving on time and materials associated with organic solvent-extraction methods. A Central Composite Face-Centred experimental design was used for the optimization of the molar ratio between PFB-Br and target analytes, the derivatization temperature, and the reaction time which were 100, 60 °C, and 180 min, respectively. Detection limits in the range 0.1-100 µM were reached using a small amount of saliva (20 µL). The use of sodium acetate-1-13C as an internal standard improved the intra- and inter-day precision of the method which ranged from 10 to 23%. The optimized protocol was successfully applied for what we believe is the first time to evaluate the salivary levels of short chain fatty acids and hydroxy acids in saliva samples of four groups of patients: i) patients admitted to hospital with acute HF symptoms, ii) patients with chronic HF symptoms, iii) patients without HF symptoms but with obesity, and iv) patients without HF symptoms but with hypertension. The first group of patients showed significantly higher levels of salivary acetic acid and lactic acid at hospital admission as well as the lowest values of hexanoic acid and heptanoic acid. Moreover, the significant high levels of acetic acid, propionic acid, and butyric acid observed in HF respect to the other patients suggest the potential link between oral bacteria and gut dysbiosis.

Assessment of the Benefit of a Deep Cleansing Gel Containing Salicylic Acid 2%, Zinc Gluconate 0.2% and Lipohydroxy Acids 0.05% in Patients with Mild to Moderate Truncal Acne: Results from an Exploratory Study.

Purpose: Acne is a skin condition of the pilosebaceous unit that affects mainly the face, chest and trunk. Approximately 50% of subjects with facial acne also have acne of the trunk. This study investigated the clinical benefit of a cleansing gel containing salicylic acid 2%, zinc gluconate 0.2% and lipohydroxy acid 0.05% in truncal acne after 84 days of daily use. Materials and Methods: A single center, open label, non-randomized study with 51 subjects with mild to moderate truncal acne was conducted. Thirty-five (35) subjects completed the study; mean age was 23 years. Inflammatory and non-inflammatory lesions, Transepidermal water loss (TEWL) and local tolerance were assessed at baseline, Day 42 and Day 84 and total lesion count was calculated. Results: The total lesion count was significantly reduced (p<0.05) after 42 days (-21.5%) and 84 days (-56.3%). Non-inflammatory lesions were significantly decreased after 84 days (-64.0%) only, while inflammatory lesions were decreased at Day 42 (-29.2%), and Day 84 (-48.2%). A statistically significant skin barrier improvement was observed at Day 84 (-21.26%). No adverse events or relevant local intolerance were reported. Conclusion: The use of the cleansing gel studied was effective in improving mild to moderate truncal acne and contributed to the skin barrier improvement. The product was well tolerated. Clintrial Data Base Identifier: NCT05584150.

Efficient determination of enantiomeric ratios of α-hydroxy/amino acids from fermented milks via ion mobility-mass spectrometry.

Chiral analysis of food components can provide important information for food quality, bioactivity and safety. Determination of enantiomeric ratios in food is a tedious task, due to the poor resolution and insufficient sensitivity for simultaneous discrimination and quantification of trace amounts of d-form metabolites. Herein, a high-throughput, high-sensitive and high-resolution method was developed for simultaneously determining enantiomeric ratios of multiple chiral α-hydroxy/amino acids (HA/AAs) from fermented milks in one-run by [d0]/[d5]-estradiol-3-benzoate-17ß-chloroformate labeling-assisted ion mobility - mass spectrometry. Results revealed extensive variation in chiral HA/AA profiles among 15 fermented milks. A total of 14 D-HA/AAs were identified. d-Lactic acid and d-alanine appeared as the most discriminatory in fermented milks with live lactic acid bacteria (LAB). Results suggested that glycolysis, casein hydrolysis and enantioisomerization of HA/AAs were most likely affected by various starter culture LAB. It may contribute to entail a valuable step forward in food quality control and discovering functional-related chiral biomarkers.

Are cosmetics based on alpha hydroxy acids safe to use when purchased over the internet?

Alpha hydroxy acids (AHAs) are used in dermatology for topical treatment of skin disorders. Some regulatory bodies, including Food and Drug Administration (FDA), recommended labeling cosmetic products with sunburn alerts and proposed limitations regarding concentrations of AHAs in cosmetic products. In addition, The Cosmetic Ingredient Review (CIR) Expert Panel recommended 10% of AHAs in products as the maximal safe concentration. With a rapidly increasing trend of online purchasing of cosmetic products, it is important that their labels convey the necessary warnings and that they be harmonized with regulatory bodies regarding the recommended concentrations of AHAs. The aim of this report was to investigate whether or not the sunburn alert, as well as AHA recommendations mostly used for exfoliating cosmetic products, was visible to consumers during the online purchasing. The compliance with FDA and CIR Expert Panel standards was analyzed in the first 50 cosmetic products obtained after the conducted investigation on the Amazon.com e-commerce company website using the search term "AHA anti-aging." It was found that exfoliating cosmetic products contained AHAs in a broad range of concentrations, from 2.5 up to 70%. Nineteen out of 50 products contained a concentration of AHAs greater than recommended. Twelve products did not contain any data at all regarding the concentration of AHAs. Sunburn alerts were present in 16 out of 50 analyzed product pages. In conclusion, more efforts should be made in providing users with information and the necessity of protection from potential complications after topical AHAs product treatments.

Portulaca oleracea extract relieves skin barrier damage induced by increased photosensitivity after GA peeling.

PURPOSE: We aimed to find active substances to help relieve the symptoms caused by increased photosensitivity after alpha hydroxy acid (AHA) peeling. METHODS: A questionnaire survey was provided to 66 patients who received AHA peeling therapy to understand if increased photosensitivity existed and its specific symptoms. We verified increased photosensitivity after AHA peeling by monitoring cell viability to detect the combined toxicity of glycolic acid (GA) and UVB in HaCaT cells. The ELISA method was used to determine the expression of KLK7, FLG, IL-1ß, and IL-8 to correlate damage to the skin barrier and inflammation induced by GA and UVB and the relieving effects of Portulaca oleracea extract. RESULTS: Our survey results showed that 6.06% of people were more sensitive to sunlight after AHA peeling than before. Experiments at the cellular level showed that UVB induced cytotoxicity on HaCaT cells pre-treated with GA. Combined exposure of GA and UVB induced up-regulation of KLK7 and down-regulation of FLG and increased inflammatory cytokines of IL-1ß and IL-8. P. oleracea extract inhibited the reduction of FLG and increased KLK7, IL-1ß, and IL-8 expression caused by combined exposure. CONCLUSIONS: Our study found that combined exposure to GA and UV disrupted the skin barrier and induced significant inflammation. These results provided a theoretical basis for increased photosensitivity after chemical peeling. P. oleracea extract ameliorated GA and UVB-induced impaired skin barrier function and inflammation in HaCaT cells and may have the potential to relieve photosensitivity after AHA peeling.

Divergent synthesis of biologically active L-threo-ß-hydroxyaspartates from common trans-oxazolidine dicarboxylate.

A divergent synthetic strategy starting from a common trans-oxazolidine dicarboxylate intermediate has been successful to produce several non-proteinogenic L-threo-ß-hydroxyaspartate derivatives efficiently with high stereoselectivity. Three bioactive α-amino-ß-hydroxy acids, L-threo-ß-hydroxyaspartic acid, L-threo-ß-hydroxyasparagine, and L-threo-ß-benzyloxyaspartic acid, were synthesized in good yields (58-83%) from the common chiral intermediate, and the chemoselective peptide bond formation at the α-amino group, ß-hydroxy group, or α-carboxylic acid of the common intermediate was possible to afford the corresponding dipeptide, tripeptide, or didepsipeptide intermediate in 46~77% yields (in three-to-four steps) due to the orthogonal protective groups on the chiral intermediate.

Direct and Selective Electrocarboxylation of Styrene Oxides with CO2 for Accessing ß-Hydroxy Acids.

Highly selective and direct electroreductive ring-opening carboxylation of epoxides with CO2 in an undivided cell is reported. This reaction shows broad substrate scopes within styrene oxides under mild conditions, providing practical and scalable access to important synthetic intermediate ß-hydroxy acids. Mechanistic studies show that CO2 functions not only as a carboxylative reagent in this reaction but also as a promoter to enable efficient and chemoselective transformation of epoxides under additive-free electrochemical conditions. Cathodically generated α-radical and α-carbanion intermediates lead to the regioselective formation of α-carboxylation products.

Electrocarboxylation of Aryl Epoxides with CO2 for the Facile and Selective Synthesis of ß-Hydroxy Acids.

Herein, an efficient and facile approach to valuable ß-hydroxy acid derivatives from readily available aryl epoxides and CO2 with high chemo- and regioselectivity under mild and sustainable electrochemical conditions is described. This approach showed broad substrate scope and good functional-group compatibility. In addition to aryl epoxides, four- to six-membered aryl cyclic ethers could all be tolerated in the reaction to provide synthetically useful hydroxy acids with high efficiency. Further late-stage carboxylation of complex molecules and drug derivatives demonstrated its potential application in the pharmaceutical industry. Mechanistic studies disclosed possible reaction pathways.

Effectiveness and safety of red yeast rice predominated by monacolin K ß-hydroxy acid form for hyperlipidemia treatment and management.

OBJECTIVE: To assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K ß-hydroxy acid form (MKA), Heye (), and Cangzhu (), compared to lifestyle modifications. METHODS: Totally 117 subjects with moderate to severe dyslipidemia (according to Chinese guidelines) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of MKA, LM plus a high dosage of MKA, and treated for 60 d. The primary endpoint was the reduction of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Safeties along with Traditional Chinese Medicine Syndromes were assessed through the study. RESULTS: A low dosage of MKA along with lifestyle modifications caused a significant decrease in LDL-C by 15.6% on average (95% , 9.6% to 21%) with, a decrease in TC by 15.3% on average (95% CI, 9.26% to 21.4%), and a decrease in non-HDL-C by 35.4% (95% CI, 25.76% to 41.34%). Weak evidence of a reduction of triglycerides but an increment of HDL-C was observed in patients with severe hyperlipidemia. No severe adverse events occurred during the study. CONCLUSION: Our results confirm the LDL-C and TC lowering properties of MKA is clinically meaningful. It also produces a significant reduction of non-HDL-C, and slightly effects on TG and HDL-C as well.

Synthesis of Terpineol from Alpha-Pinene Catalyzed by α-Hydroxy Acids.

We report the use of five alpha-hydroxy acids (citric, tartaric, mandelic, lactic and glycolic acids) as catalysts in the synthesis of terpineol from alpha-pinene. The study found that the hydration rate of pinene was slow when only catalyzed by alpha-hydroxyl acids. Ternary composite catalysts, composed of AHAs, phosphoric acid, and acetic acid, had a good catalytic performance. The reaction step was hydrolysis of the intermediate terpinyl acetate, which yielded terpineol. The optimal reaction conditions were as follows: alpha-pinene, acetic acid, water, citric acid, and phosphoric acid, at a mass ratio of 1:2.5:1:(0.1-0.05):0.05, a reaction temperature of 70 °C, and a reaction time of 12-15 h. The conversion of alpha-pinene was 96%, the content of alpha-terpineol was 46.9%, and the selectivity of alpha-terpineol was 48.1%. In addition, the catalytic performance of monolayer graphene oxide and its composite catalyst with citric acid was studied, with acetic acid used as an additive.

Effectiveness of a cosmetic device containing a combination of alpha- and beta-hydroxy acids, urea, and thuja for the treatment of seborrheic keratoses.

BACKGROUND: Seborrheic keratosis is a benign epidermal tumor of cosmetic concern-as it progressively increases in size, thickness, and pigmentation-on which topical treatments are poorly effective. Considering its keratotic component, effective products may include active principles with keratolytic action. AIMS: Evaluate the efficacy and tolerability of a topical cosmetic product with urea and hydroxy acids, in the treatment of seborrheic keratoses. PATIENTS AND METHODS: Twenty patients were enrolled in an observational, prospective, open-label study. The topical device was applied on seborrheic keratoses twice daily for 30 days. We evaluated the progression of the treatment by clinical examination-using Daily Life Quality Index-and epiluminescence microscopy at baseline and day 30. RESULTS: After 30 days of treatment, we documented a significant reduction in seborrheic keratosis thickness and number, which was confirmed also by epiluminescence microscopy. On day 30, global Daily Life Quality Index improved by 99.95%. The tolerability of the cosmetic device was considered excellent, according to 19/20 subjects (95%). CONCLUSIONS: The results of our study showed the efficacy and tolerability of this cosmetic device. Its active compounds favor gradual removal of seborrheic keratoses, even in case of pigmented variants. This non-invasive treatment represents an alternative to surgical procedures, mainly for fragile patients and delicate skin areas. It is possible to speculate its usefulness in the topical treatment of circumscribed hyperkeratosis, palmoplantar keratoderma, and thick psoriatic plaques.

Peculiarities of Aluminum Anodization in AHAs-Based Electrolytes: Case Study of the Anodization in Glycolic Acid Solution.

The anodization of aluminum (Al) in three alpha-hydroxy acids (AHAs): glycolic (GC), malic (MC), and citric (CC), was analyzed. Highly ordered pores in GC were obtained for the first time. However, the hexagonal cells were characterized by a non-uniform size distribution. Although common features of current density behavior are visible, the anodization in AHAs demonstrates some peculiarities. The electric conductivity (σ) of 0.5 M GC, MC, and CC electrolytes was in the following order: σ(CC) > σ(MC) > σ(GC), in accordance with the acid strength pKa(CC) < pKa(MC) < pKa(GC). However, the anodization voltage, under which a self-organized pore formation in anodic alumina (AAO) was observed (Umax), decreased with increasing pKa: Umax(CC) > Umax(MC) ≥ Umax(GC). This unusual behavior is most probably linked with the facility of acid ions to complex Al and the active participation of the Al complexes in the AAO formation. Depending on the AHA, its tendency and different modes to coordinate Al ions, the contribution of stable Al complexes to the AAO growth is different. It can be concluded that the structure of Al complexes, their molecular mass, and the ability to lose electrons play more important roles in the AAO formation than pKa values of AHAs.

Efficient enantioresolution of aromatic α-hydroxy acids with Cinchona alkaloid-based zwitterionic stationary phases and volatile polar-ionic eluents.

Single enantiomers of mandelic acid (1), 3-phenyllactic acid (2), and 3-(4-hydroxyphenyl)lactic acid (3) are the subject of many fields of investigation, spanning from the pharmaceutical synthesis to that of biocompatible and biodegradable polymers, while passing from the interest towards their antimicrobial activity to their role as biomarkers of particular pathological conditions or occupational exposures to specific xenobiotics. All above mentioned issues justify the need for accurate analytical methods enabling the correct determination of the individual enantiomers. So far, all the developed liquid chromatography (LC) methods were not or hardly compatible with mass spectrometry (MS) detection. In this paper, a commercially available Cinchona-alkaloid derivative zwitterionic chiral stationary phase [that is, the CHIRALPAK® ZWIX(-)] was successfully used to optimize the enantioresolution of compounds 1-3 under polar-ionic (PI) conditions with a mobile phase consisting of an acetonitrile/methanol 95/5 (v/v) mixture with 80 mM formic acid. With the optimized conditions, enantioseparation and enantioresolution values up to 1.46 and 4.41, respectively, were obtained. In order to assess the applicability of the optimized enantioselective chromatography conditions in real-life scenarios and on MS-based systems, a proof-of-concept application was efficiently carried out by analysing dry urine spot samples spiked with 1 by means of a LC-MS system. The (S)<(R) enantiomer elution order (EEO) was established for compounds 1 and 2 by analysing a pure enantiomeric standard of known configuration. This was not possible for 3 because not commercially available. For this compound, the same EEO was identified applying a procedure based on ab initio time-dependent density-functional theory simulations coupled to electronic circular dichroism analyses. Moreover, a molecular dynamics simulation unveiled the role of the phenolic OH in compound 3 in the retention mechanism.

Synthesis of Functionalized Aliphatic Acid Esters via the Generation of Alkyl Radicals from Silylperoxyacetals.

We describe a catalytic method for the synthesis of a variety of functionalized aliphatic acid esters using silylperoxyacetals, which are versatile alkyl radical precursors with a terminal ester moiety. In the presence of an appropriate transition-metal catalyst, the in situ generation of alkyl radicals and the subsequent bond-forming process proceeds smoothly to afford synthetically valuable aliphatic acid derivatives. The present method can be applied to the efficient synthesis of a pharmaceutically important 1,1-diarylalkane motif. In addition, a novel strategy for the synthesis of structurally diverse hydroxy acid derivatives via a C-O bond formation process that utilizes TEMPO has been developed.