Hydroxy Acids Research Articles

Kinetics of the thermal decomposition of thermally reduced graphene oxide treated with a pulsed high-frequency discharge in hydrogen atmosphere

Thermal stability and the kinetics of thermal decomposition of the thermally reduced graphene oxide (TRGO) treated by a pulsed high-frequency discharge in a hydrogen atmosphere have been studied. The modified Hummers method was used for obtaining the initial graphite oxide from graphite powder. Thermal exfoliation of the graphene oxide powder has been done in vacuum conditions with a heating rate of 5–7 degrees per minute to a temperature of 300 °С. TRGO has been treated by pulsed high-frequency discharge in a hydrogen atmosphere for partial graphene hydrogenation (chemical addition of atomic hydrogen) that leads to structural changes in the carbon planes and formation of C–H sp3 bonds. The thermogravimetry analysis measurements of the mass loss have been carried from room temperature to 1000 °C in a nitrogen atmosphere with a nitrogen flow rate of 20 mL/min and different heating rates: 50, 75 100, 125, 150, and 200 K/min, respectively. Kissinger’s multiple heating rate method has been used to determine the activation energy for decomposing substances. Activation energies Ea1, Ea2, and Ea3 equal 28, 50, and 148 kJ/mol, respectively, have been compared with the energies of the activation of thermal defunctionalization of multiwalled carbon nanotubes (MWCNTs). The activation energy Ea3 = 148 kJ/mol is close to that of the thermal decomposition of anhydride functional groups in MWCNT. The value of Ea2 = 50 kJ/mol indicates the presence of the keto and hydroxy acid’s function groups on TRGO. Activation energy Ea1 = 28 kJ/mol related with all other groups including the lighter C–H bonds that destructed due to dehydrogenation of the TRGO. Obtained experimental results are useful for further proposing the kinetic model of the mechanism of the most probable reaction of TRGO decomposition.

The study of rate constants of redox reactions on cobalt (III) complexes of α-hydroxy acids with quinolinium chlorochromate (QCC) in micellar medium

Complexes of QCC with bound and unbound alpha-hydroxy acids of Co (III) in the micellar medium is unable to obtain some sort of electron transport mode kinetics in the medium. Unbound and bound hydroxy acids are oxidised by QCC, which also oxidizes Cobalt (III). The Cobalt (III) centre cannot receive an electron while the C-C bond is being split. These compounds’ oxidation rates rise in direct proportion to their temperature. When the concentration of surfactant is increased, the rate increases. More than ammonium laurylsuphate, DDAC can speed up the oxidation of the process (ALS). A similar pattern was found in the Co (III) complexes containing lactato, glycolato, and mandelato.

Synthesis of hydroxy acids via the light-driven carboxylation of epoxides with CO2

Synthesis of hydroxy acids via the light-driven carboxylation of epoxides with CO2

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

Enantioseparation of -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 thefood industry to ensure quality. HPLC methods were developed for the enantioselective separation of 11 -hydroxy acids using asuperficially 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.

Combating Alcohol Adduct Impurity in Immunosuppressant Drug Product Manufacturing: A Scientific Investigation for Enhanced Process Control.

This research aims to elucidate critical impurities in process validation batches of tacrolimus injection formulations, focusing on identification and characterization of previously unreported impurity at RRT 0.42, identified as the tacrolimus alcohol adduct. The potential root causes for the formation of new impurity was determined using structured risk assessment by cause and effect fishbone diagram. The primary objective was to propose mitigation plan and demonstrate the control of impurities with 6 month accelerated stability results in development batches. The investigation utilizes method validation and characterization studies to affirm the accuracy of quantifying the tacrolimus alcohol adduct. The research methodology employed different characterization techniques like rotational rheometer, ICP‒MS, MALDI-MS, 1H NMR, 13C NMR, and DEPT-135 NMR for structural elucidation. Additionally, the exact mass of the impurity is validated using electrospray ionization mass spectra. Results indicate successful identification and characterization of the tacrolimus alcohol adduct. The study further explores the transformation of Tacrolimus monohydrate under various conditions, unveiling the formation of Tacrolimus hydroxy acid and proposing the existence of a novel degradation product, the Tacrolimus alcohol adduct. Six-month data from development lots utilizing Manufacturing Process II demonstrate significantly lower levels of alcohol adducts. Manufacturing Process II, selectively locates Tacrolimus within the micellar core of HCO-60, this prevent direct contact of ethanol with Tacrolimus which minimizes impurity alcohol adduct formation. This research contributes to the understanding of tacrolimus formulations, offering ways to safeguard product integrity and stability during manufacturing and storage.

Engineering Biocatalysts for the C−H Activation of Fatty Acids by Ancestral Sequence Reconstruction**

AbstractSelective, one‐step C−H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high‐value hydroxy acids, but to date enzyme discovery has relied on laborious screening and produced limited hits, which predominantly oxidise the subterminal positions of fatty acids. Herein we show that ancestral sequence reconstruction (ASR) is an effective tool to explore the sequence‐activity landscape of a family of multidomain, self‐sufficient P450 monooxygenases. We resurrected 11 catalytically active CYP116B ancestors, each with a unique regioselectivity fingerprint that varied from subterminal in the older ancestors to mid‐chain in the lineage leading to the extant, P450‐TT. In lineages leading to extant enzymes in thermophiles, thermostability increased from ancestral to extant forms, as expected if thermophily had arisen de novo. Our studies show that ASR can be applied to multidomain enzymes to develop active, self‐sufficient monooxygenases as regioselective biocatalysts for fatty acid hydroxylation.

Engineering Biocatalysts for the C-H Activation of Fatty Acids by Ancestral Sequence Reconstruction.

Selective, one-step C-H activation of fatty acids from biomass is an attractive concept in sustainable chemistry. Biocatalysis has shown promise for generating high-value hydroxy acids, but to date enzyme discovery has relied on laborious screening and produced limited hits, which predominantly oxidise the subterminal positions of fatty acids. Herein we show that ancestral sequence reconstruction (ASR) is an effective tool to explore the sequence-activity landscape of a family of multidomain, self-sufficient P450 monooxygenases. We resurrected 11 catalytically active CYP116B ancestors, each with a unique regioselectivity fingerprint that varied from subterminal in the older ancestors to mid-chain in the lineage leading to the extant, P450-TT. In lineages leading to extant enzymes in thermophiles, thermostability increased from ancestral to extant forms, as expected if thermophily had arisen de novo. Our studies show that ASR can be applied to multidomain enzymes to develop active, self-sufficient monooxygenases as regioselective biocatalysts for fatty acid hydroxylation.

Modelling of reaction kinetics in production of hydroxy carboxylic acids by alkaline degradation of cellulosic waste

The reaction kinetics in alkaline degradation of cellulosic materials to monomeric compounds at elevated temperatures was studied. The target compounds are hydroxy carboxylic acids, preferably glucoisosaccharinic acid (GISA), that are valuable platform chemicals. This methodology, which focuses on depolymerizing cellulosic materials and transforming them into hydroxy carboxylic acids, has not been explored in existing literature. To this end, a rigorous mathematical model was developed that considers phenomena at macroscopic level (transformation of crystalline cellulose into amorphous) and at microscopic level (cleavage of glycosidic bonds). Experimental cellulose degradation data in 10 wt-% NaOH and 20–200 °C was correlated with the model. The agreement between the model results and the experimental data confirmed that the process obeys the proposed reaction pathway. Around 80 % of degradation occurs during the reactor warming up period. Analysis of rate constants indicates that GISA is not degraded into smaller hydroxy acids (SHA) at the temperatures studied. Instead, monosaccharides are converted into SHA as soon as they are produced. Conversion of crystalline cellulose into amorphous form was identified as the rate determining step.

Uniformly coated Cu@Ag core-shell particles with low silver content: Hydroxy acid as a complexing agent with “double-sided adhesive” function

The Cu@Ag core-shell particles are the highly anticipated functional materials in electronic applications which are required to be high electrical conductivity, good thermal properties and low cost. However, it remains a challenge to obtain a completely and uniformly coated Ag shell in low silver content. During the coating process, it is essential to regulate the reduction of Ag+ on the surface of Cu to ensure uniformly silver shell. We developed a strategy to prepare uniformly coated Cu@Ag particles by employing hydroxy acids as complexing agents with “double-sided adhesive” function. Compared to conventional complexing agents, the employed hydroxy acids can not only coordinate with Ag+ but also complex with Cu due to the more carboxyl and hydroxyl groups which act like a “double-sided adhesive”, that can pull Ag+ to the surface of Cu, and then accomplish the coating of Ag with replacement and reduction reaction. The impact of different types of hydroxy acids as complexing agents on the coating effect of silver-clad copper powder was investigated when the silver addition was 15 %. Results indicated that the obtained Cu@Ag particles with tannic acid as complexing agent show high coating quality layer with low surface sliver content (11.4 %). Moreover, the obtained Cu@Ag particles exhibit good dispersibility, promising thermal stability and low electrical resistivity (30 μΩ·cm).

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults.

Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05). Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

A comprehensive review of the ecological significance, pharmacological potential and economic importance of Samanea saman

Samanea saman belongs to the Leguminosae family commonly known as rain tree. The phytochemical screening of S. saman revealed the presence of many secondary metabolites such as alkaloids, pithecolobine and saponin (Samarin) which have been used for the treatment of different diseases. Natural products from plants have been used as therapeutic drugs throughout the world. This review is mainly focused on the morphology, distribution and phytochemicals contributing to the pharmacological properties of S.saman.

Evaluation of an advanced antioxidant and double-conjugated retinoid/AHA cream in participants with FST IV-V.

Topical antioxidants and retinoids are foundational components of an effective skincare regimen. Pyrroloquinoline quinone (PQQ) is a potent free radical scavenger that supports efficient mitochondrial energy creation. An advanced antioxidant combines topical allyl PQQ with existing WEL antioxidant technology (TAP) to comprehensively address extrinsic and intrinsic skin aging. In conjunction with TAP, a double-conjugated retinoid/alpha hydroxy acid (AHA-Ret) designed to minimize irritation and optimize delivery was used over 12 weeks to improve the appearance of photodamaged skin. Twice-daily application of TAP and nightly application of AHA-Ret was evaluated in female participants aged 40-65 years with FST IV-V and mild (3) to moderate (6) facial photodamage using a 10-point grading scale. Visible improvements from baseline in lines/wrinkles, skin texture, skin tone, skin dullness and erythema were assessed using a six-point grading scale (0 = None to 5 = Severe). Adverse Events (AEs) were captured throughout the study period. Participants (N = 21; mean age, 56 years) equally represented mild and moderate photodamage, and FST IV and V (41%, Hispanic; 36%, African American; and 32%, Caucasian). Significant mean improvements from baseline occurred in skin dullness, skin texture, and skin tone (all, p < 0.0001), and significant mean reductions from baseline were demonstrated in erythema and melanin at Week 12. Mild, transient AEs were reported. No participant discontinued study participation due to an AE. A skincare regimen comprised of an advanced antioxidant and AHA-Ret cream, in conjunction with daily use of a broad-spectrum sunscreen (SPF 56), led to significant improvements at 12 weeks in the appearance of photodamaged skin in females with FST IV and V.

Another renaissance for bile acid gastrointestinal microbiology.

The field of bile acid microbiology in the gastrointestinal tract is going through a current rebirth after a peak of activity in the late 1970s and early 1980s. This renewed activity is a result of many factors, including the discovery near the turn of the century that bile acids are potent signalling molecules and technological advances in next-generation sequencing, computation, culturomics, gnotobiology, and metabolomics. We describe the current state of the field with particular emphasis on questions that have remained unanswered for many decades in both bile acid synthesis by the host and metabolism by the gut microbiota. Current knowledge of established enzymatic pathways, including bile salt hydrolase, hydroxysteroid dehydrogenases involved in the oxidation and epimerization of bile acid hydroxy groups, the Hylemon-Bjӧrkhem pathway of bile acid C7-dehydroxylation, and the formation of secondary allo-bile acids, is described. We cover aspects of bile acid conjugation and esterification as well as evidence for bile acid C3-dehydroxylation and C12-dehydroxylation that are less well understood but potentially critical for our understanding of bile acid metabolism in the human gut. The physiological consequences of bile acid metabolism for human health, important caveats and cautionary notes on experimental design and interpretation of data reflecting bile acid metabolism are also explored.

Bio-upcycling of even and uneven medium-chain-length diols and dicarboxylates to polyhydroxyalkanoates using engineered Pseudomonas putida

Bio-upcycling of plastics is an emerging alternative process that focuses on extracting value from a wide range of plastic waste streams. Such streams are typically too contaminated to be effectively processed using traditional recycling technologies. Medium-chain-length (mcl) diols and dicarboxylates (DCA) are major products of chemically or enzymatically depolymerized plastics, such as polyesters or polyethers. In this study, we enabled the efficient metabolism of mcl-diols and -DCA in engineered Pseudomonas putida as a prerequisite for subsequent bio-upcycling. We identified the transcriptional regulator GcdR as target for enabling metabolism of uneven mcl-DCA such as pimelate, and uncovered amino acid substitutions that lead to an increased coupling between the heterologous β-oxidation of mcl-DCA and the native degradation of short-chain-length DCA. Adaptive laboratory evolution and subsequent reverse engineering unravelled two distinct pathways for mcl-diol metabolism in P. putida, namely via the hydroxy acid and subsequent native β-oxidation or via full oxidation to the dicarboxylic acid that is further metabolized by heterologous β-oxidation. Furthermore, we demonstrated the production of polyhydroxyalkanoates from mcl-diols and -DCA by a single strain combining all required metabolic features. Overall, this study provides a powerful platform strain for the bio-upcycling of complex plastic hydrolysates to polyhydroxyalkanoates and leads the path for future yield optimizations.Graphical

Free Fatty Acid Determination in Broccoli Tissues Using Liquid Chromatography-High-Resolution Mass Spectrometry.

Broccoli (Brassica oleracea L. var. italica Plenck) is a widely consumed vegetable, very popular due to its various nutritional and bioactive components. Since studies on the lipid components of broccoli have been limited so far, the aim of the present work was the study of free fatty acids (FFAs) present in different broccoli parts, aerial and underground. The direct determination of twenty-four FFAs in broccoli tissues (roots, leaves, and florets) was carried out, using a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method in a 10 min single run. Linolenic acid was found to be the most abundant FFA in all different broccoli parts in quantities ranging from 0.76 to 1.46 mg/g, followed by palmitic acid (0.17-0.22 mg/g) and linoleic acid (0.06-0.08 mg/g). To extend our knowledge on broccoli's bioactive components, for the first time, the existence of bioactive oxidized fatty acids, namely hydroxy and oxo fatty acids, was explored in broccoli tissues adopting an HRMS-based lipidomics approach. 16- and 2-hydroxypalmitic acids were detected in all parts of broccoli studied, while ricinoleic acid was detected for the first time as a component of broccoli.

Adding α,α-disubstituted and β-linked monomers to the genetic code of an organism

The genetic code of living cells has been reprogrammed to enable the site-specific incorporation of hundreds of non-canonical amino acids into proteins, and the encoded synthesis of non-canonical polymers and macrocyclic peptides and depsipeptides1–3. Current methods for engineering orthogonal aminoacyl-tRNA synthetases to acylate new monomers, as required for the expansion and reprogramming of the genetic code, rely on translational readouts and therefore require the monomers to be ribosomal substrates4–6. Orthogonal synthetases cannot be evolved to acylate orthogonal tRNAs with non-canonical monomers (ncMs) that are poor ribosomal substrates, and ribosomes cannot be evolved to polymerize ncMs that cannot be acylated onto orthogonal tRNAs—this co-dependence creates an evolutionary deadlock that has essentially restricted the scope of translation in living cells to α-l-amino acids and closely related hydroxy acids. Here we break this deadlock by developing tRNA display, which enables direct, rapid and scalable selection for orthogonal synthetases that selectively acylate their cognate orthogonal tRNAs with ncMs in Escherichia coli, independent of whether the ncMs are ribosomal substrates. Using tRNA display, we directly select orthogonal synthetases that specifically acylate their cognate orthogonal tRNA with eight non-canonical amino acids and eight ncMs, including several β-amino acids, α,α-disubstituted-amino acids and β-hydroxy acids. We build on these advances to demonstrate the genetically encoded, site-specific cellular incorporation of β-amino acids and α,α-disubstituted amino acids into a protein, and thereby expand the chemical scope of the genetic code to new classes of monomers.

Exploring the hidden treasures: Deep-sea bacterial community structure in the Bay of Bengal and their metabolic profile

Deep sea bacterial communities demonstrate remarkable adaptability to high-pressure environments coupled with low temperatures which has sparked curiosity about their diversity and exceptional metabolic pathways. Additionally, bacteria in the deep sea exert a substantial influence over various biogeochemical processes. To date, we have relatively very little information about the deep-sea bacterial communities and, they remain largely unexplored. We investigated the variability in the physicochemical conditions, heavy metals and their influence on deep-sea bacterial community structure across three different depths in the Bay of Bengal. The structural and metabolic diversity of deep-sea sediment microbial communities were examined through culture-based sequencing of 16S rRNA genes, ecto-enzymatic studies, and community-level physiological profiling. Bacillota was the most dominant phylum representing 61% of the cultured bacterial isolates, while the remaining belonged to Actinomycetota and Pseudomonodata. Five potential novel species belonging to the genera Fictibacillus, Lysinibacillus, Salinicola, Robertmurraya and Blastococcus were identified. The extracellular enzymatic activity was positive for &amp;gt;50% of the bacterial isolates, wherein the genera Bacillus and Micromonospora exhibited versatile profiles. High metabolic diversity was recorded through the carbon substrate utilization profiles indicating that microbial communities are active participants in biogeochemical cycles in the deep sea. The most prominently utilized carbon substrates were α-cyclodextrin, glucose-1-phosphate, D-xylose, glycogen, and 2-hydroxy benzoic acid which serve as organic substrates for microbial metabolism, facilitating the decomposition of organic matter and, recycling carbon in deep-sea ecosystems. Multivariate statistical analyses confirmed that the environmental variables had a profound influence on the bacterial community. The findings shed light on spatial variability in the bacterial community structure, enzyme activity and metabolic profiles, and enhance our understanding of Bay of Bengal deep-sea sedimentary microbial ecology.

Lipid composition, caloric content, and novel oxidation products from microbial communities within seasonal pack ice cores

Sea ice is a critical feature of polar environments with importance for coastal ecosystems. Along the West Antarctic Peninsula (WAP), climate change is causing decreases in seasonal sea ice duration and extent. Organic carbon within sea ice is an important aspect of southern ocean carbon cycling but less studied than water column or sedimentary carbon reservoirs. Though conditions within sea ice can be extreme, phytoplankton are able to flourish and serve as a key food source for higher trophic levels, especially in the spring and fall. A portion of this sea ice phytoplankton biomass is composed of lipids, which are both calorically dense and useful as tracers of biological processes within the sea ice. To better understand both the trophic value and the diversity of lipids present within sea ice we employed high-resolution accurate-mass mass spectrometry to analyze ice core samples from six sites collected along the peninsula in November 2018. Using untargeted methods we annotated 1,173 intact lipid species across 14 classes of intact polar lipids, triacylglycerols, and pigments. We compared lipids’ physical distribution within sea ice cores and found they are highly geographically and physically heterogenous within sites. Ratios between intact polar lipid classes show little signs of phytoplankton nutrient stress; a finding consistent with internally nutrient replete sea ice brines. We found key differences in the composition between pack ice versus fast ice and observed chlorophyll a to be inconsistently correlated with triacylglycerol content. We determined the mean caloric content of lipids within pack ice (4.45 ± 3.47 kJ m−2) and found that caloric densities from the lipids alone were in the range of total water column energy content. Lastly, we show evidence of fatty acid hydroxy fatty acid triacylglycerols within the ice matrix and discuss possible biochemical sources of these novel biomarkers in an ocean system. These results shed light on the chemical diversity of a dynamic and ecosystem relevant carbon pool.

Versatile capillary electrophoresis method for the direct chiral separation of aliphatic and aromatic α-hydroxy acids, β-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 α-hydroxy acid (AHA) enantiomers, aliphatic β-hydroxy 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.

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. 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. 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. 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.