Roccaldo Sardella - Academia.edu (original) (raw)

Papers by Roccaldo Sardella

Research paper thumbnail of Improved chromatographic diastereoresolution of cyclopropyl dafachronic acid derivatives using chiral anion exchangers

Journal of Chromatography A, Jul 1, 2018

Research paper thumbnail of Effect of Cocoa Roasting on Chocolate Polyphenols Evolution

Antioxidants

Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood fl... more Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood flow improvement or blood pressure and glycemia reduction, as well as cognitive function improvement. Unfortunately, polyphenol content is reduced during cocoa fermentation, drying, roasting and all the other phases involved in the chocolate production. Here, we investigated the evolution of the polyphenol content during all the different steps of chocolate production, with a special emphasis on roasting (3 different roasting cycles with 80, 100, and 130 °C as maximum temperature). Samples were followed throughout all processes by evaluating the total polyphenols content, the antioxidant power, the epicatechin content, and epicatechin mean degree of polymerization (phloroglucinol adducts method). Results showed a similar trend for total polyphenol content and antioxidant power with an unexpected bell-shaped curve: an increase followed by a decrease for the three different roasting temperat...

Research paper thumbnail of Multiple Heart-Cutting Two-Dimensional HPLC-UV Achiral–Chiral Analysis of Branched-Chain Amino Acids in Food Supplements under Environmentally Friendly Conditions

Separations

A multiple heart-cutting (mLC-LC) two-dimensional HPLC-UV achiral–chiral method for the direct an... more A multiple heart-cutting (mLC-LC) two-dimensional HPLC-UV achiral–chiral method for the direct analysis of branched-chain amino acids (BCAAs) in food supplements under environmentally friendly conditions was developed to cope with the very well-known limited chemoselectivity of chromatographic media for enantioselective analysis. Both achiral and chiral methods were developed in compliance with the main principles of green chromatography. The achiral analysis was performed isocratically with an optimized ion-pair reversed-phase (IP-RP) method based on a water/EtOH (95:5, v/v) mobile phase containing heptafluorobutyric acid (7 mM) as the IP agent. The achiral method was characterized by a very appreciable performance and was validated before the analysis of the real sample. High recovery values for all compounds (from 97% to 101%) were found in the interday evaluation. Additionally, low RSD% values in the long-term period were measured, in the range between 1.1% and 4.8%. Still, an L...

Research paper thumbnail of Combining molecular modeling approaches to establish the chromatographic enantiomer elution order in the absence of pure enantiomeric standards: A study case with two tetracyclic quinolines

Research paper thumbnail of Separation and determination of cysteine enantiomers in plasma after derivatization with 4-fluoro-7-nitrobenzofurazan

Journal of Pharmaceutical and Biomedical Analysis, 2022

The importance of D-amino acids in mammals associated with enantio-dependent biological functions... more The importance of D-amino acids in mammals associated with enantio-dependent biological functions has been increasingly highlighted. In addition to naturally occurring, D-amino acid supplementation could have a positive biological impact, including cytoprotective implications. In this context, supplementation with D-cysteine has revealed beneficial effects. Quantification of cysteine enantiomers in rodent plasma has been achieved by using 4-fluoro-7-nitrobenzofurazan derivatization of the target analytes. Cystine, the main form of cysteine in the plasma, was initially reduced to cysteine using DL-dithiothreitol. Baseline enantioseparation was then achieved in less than 3 min using a (R,R)-Whelk-O 1 stationary phase and isocratic elution using CH3OH-H2O 90:10 (v/v) with 15 mM ammonium formate (apparent pH 6.0) at 0.5 mL/min. The derivatives were then detected using negative ESI-MS in SRM mode. An external calibration was employed for D-cysteine, while L-cysteine quantification, as an endogenous analyte, was addressed using a background subtraction strategy. The method was validated. Response functions were obtained from 0 to 300 µM and from 0 to 125 µM for D-cysteine and L-cysteine, respectively. The trueness ranged from 96% to 105% for both enantiomers with repeatability and intermediate precision lower than 8% and 15% for the D-form and the endogenous L-form, respectively. The method was successfully applied for determining D- and L-cysteine in mouse plasma after D-cysteine administration.

Research paper thumbnail of Short Communication (S)-(-)-a,a-Di(2-naphthyl)-2-pyrrolidinemethanol, a useful tool to study the recognition mechanism in chiral ligand-exchange chromatography

Research paper thumbnail of Use of a Zwitterionic Surfactant to Improve the Biofunctional Properties of Wool Dyed with an Onion (Allium cepa L.) Skin Extract

Antioxidants, 2020

To improve the loadability and antioxidant properties of wool impregnated with onion skin extract... more To improve the loadability and antioxidant properties of wool impregnated with onion skin extract, the introduction of SB3-14 surfactant in the dyeing process was evaluated. A preliminary investigation on the surfactant–quercetin interaction indicated that the optimal conditions for dye solubility, stability, and surfactant affinity require double-distilled water (pH = 5.5) as a medium and SB3-14 in a concentration above the c.m.c. (2.5 × 10−3 M). The absorption profile of textiles showed the flavonoid absorption band (390 nm) and a bathochromic feature (510 nm), suggesting flavonoid aggregates. The higher absorbance for the sample dyed with SB3-14 indicated greater dye uptake, which was further confirmed by HPLC analysis. The Folin–Ciocalteu method was applied to evaluate the total phenol content (TPC) released from the treated wool, while the assays FRAP, DPPH, ABTS, and ORAC were applied to evaluate the corresponding total antioxidant activity (TAC). Higher TPCs (about 20%) and T...

Research paper thumbnail of Antioxidant Power on Dermal Cells by Textiles Dyed with an Onion (Allium cepa L.) Skin Extract

Antioxidants, 2021

In this study, the phenol loading and antioxidant activity of wool yarn prepared with the aqueous... more In this study, the phenol loading and antioxidant activity of wool yarn prepared with the aqueous extract of onion (Allium cepa L.) skin was enhanced by implementing the dyeing process with the use of alum as a mordant. Spectrophotometric and chromatographic methods were applied for the characterization of polyphenolic substances loaded on the wool yarn. The antioxidant/anti-inflammatory properties were evaluated by determining the level of intra- and extra-cellular reactive oxygen species (ROS) production in keratinocytes and dermal fibroblasts pre-treated with lipopolysaccharide put in contact with artificial sweat. An elevated dye uptake on wool was observed for the pre-mordanted sample, as demonstrated by high absorbance values in the UV-Visible spectral range. Chromatographic results showed that protocatechuic acid and its glucoside were the main phenolic acid released in artificial sweat by the wool yarns, while quercetin-4′-glucoside and its aglycone quercetin were more retai...

Research paper thumbnail of Laboratory-Scale Semipreparative Enantioresolution of Phenylethanolic-Azole Heme Oxygenase-1 Inhibitors

Chromatographia, 2020

In the present work, the development and application of two HPLC methods enabling the semiprepara... more In the present work, the development and application of two HPLC methods enabling the semipreparative enantioresolution of 1-(biphenyl-3-yl)-2-(1H-imidazol-1-yl)ethanol (1) and 1-[4-[(4-bromobenzyl)oxy]phenyl]-2-(1H-imidazol-1-yl)ethanol (2), two among the most potent and selective heme oxygenase-1 (HO-1) inhibitors known, are described. During the optimization step, different chiral stationary phase (CSP) features were evaluated, especially focusing the attention on (1) the type (electron-donating and electron-withdrawing) and position of the substituents in the phenyl moiety; (2) the physical coating or covalent immobilization of the modified polymer chain. Additionally, the effect of different types and amount of alcohol in the normal-phase eluent as well as of the column temperature, were investigated. For compound 1, Lux Cellulose-1 CSP containing cellulose tris(3,5-dimethylphenylcarbamate) was identified as the optimal choice in combination with a mobile phase consisting of n-hexane/ethanol-85/15 (v/v). Conversely, for compound 2, Lux Cellulose-2 CSP containing the cellulose tris(3-chloro-4-methyl phenylcarbamate)-based chiral selector was identified as the optimal choice, running the analysis with a n-hexane/ethanol/2-propanol-80/15/5 (v/v/v) mobile phase.

Research paper thumbnail of Optimized one-pot derivatization and enantioseparation of cysteine: Application to the study of a dietary supplement

Journal of Pharmaceutical and Biomedical Analysis, 2020

Cysteine is a sulfur-containing amino acid which plays an outstanding role in many biological pat... more Cysteine is a sulfur-containing amino acid which plays an outstanding role in many biological pathways in mammals. The analysis and quantification of native cysteine remains a critical issue due to its highly reactive thiol group evolving to the disulfide cystine derivative through oxidation reaction. Aimed at improving the derivative stability, cysteine was labelled with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), which reacts with both amino and thiol groups. The derivatization was optimized and the chemical identity of the reaction product was assessed via high-resolution mass spectrometry. The NBD-cysteine derivative resulted stable for 10 days. This derivative was enantioresolved (α and RS equal to 1.25 and 2.70, respectively) thanks to a (R,R)-Whelk-O1 phase with the following chromatographic setting: eluent, MeOH/water-90/10 (v/v) with 15 mM ammonium formate (pwsH 6.0); column temperature, 35 °C; flow rate, 1.0 mL/min. The developed method was validated following the ICH guidelines and applied for the quality control of a L-cysteine containing dietary supplement.

Research paper thumbnail of Enantioselective high-performance liquid chromatography analysis of oxygenated polyunsaturated fatty acids

Free Radical Biology and Medicine, 2019

Oxygenated polyunsaturated fatty acids (PUFAs)play an outstanding role in the physiological and p... more Oxygenated polyunsaturated fatty acids (PUFAs)play an outstanding role in the physiological and pathological regulation of several biological processes. These oxygenated metabolites can be produced both enzimatically, yielding almost pure enantiomers, and non-enzymatically. The free radical-mediated non-enzymatic oxidation commonly produces racemic mixtures which are used as biomarkers of oxidative stress and tissue damage. The biological activity of oxygenated PUFAs is often associated with only one enantiomer, making it necessary of availing of lipidomics platforms allowing to disclose the role of single enantiomers in health and disease. Polysaccharide-based chiral stationary phases (CSPs) play a dominating part in this setting. As for the cellulose backbone, 4-methylbenzoate derivatives exhibit very high chiral recognition ability towards this class of compounds. Concerning the phenylcarbamate derivatives of cellulose and amylose, the tris(3,5-dimethylphenylcarbamate) variants show the best enantioresolving ability for a variety of oxygenated PUFAs. Moreover, also the amylose tris(5-chloro-2-methylphenylcarbamate)-based selector produces relevant chromatographic performances. The extreme versatility of those CSPs mostly depends on their compatibility with the most relevant elution modes: normal- and reversed-phase, as well as polar organic/ionic-mode. In this review article, a selection of enantioseparation studies of different oxygenated PUFAs is reported, with both tris(benzoates) and tris(phenylcarbamates) of cellulose and amylose.

Research paper thumbnail of Last ten years (2008-2018) of chiral ligand-exchange chromatography in HPLC: An updated review

Journal of Separation Science, 2018

Chiral ligand-exchange chromatography is one of the elective strategies for the direct enantiores... more Chiral ligand-exchange chromatography is one of the elective strategies for the direct enantioresolution of small chelating compounds: amino acids, diamines, amino alcohols, diols, small peptides, etc. Unlike other methods, the interaction between chiral selector and analyte enantiomers is mediated by a cation, thus producing diastereomeric ternary complexes. Two main approaches are conventionally applied in chiral ligand-exchange chromatography. The first relies upon chiral stationary phases where the chiral selector is either covalently immobilized or physically adsorbed onto suitable packing materials (coated phases). In the second approach, chiral molecules are added to the eluent, thus generating chiral eluent systems. Among the advantages of chiral ligand-exchange chromatography, the generation of UV/vis-active metal complexes, and the use of commercially available or easy-to-synthesize chiral selectors, in combination to rather inexpensive achiral columns for coated phases and chiral eluents, are noteworthy. Besides amino acids and amino alcohols, other species have proven suitable for chiral ligand-exchange chromatography applications. Recently, the use of either chiral ionic liquids or micellar liquid chromatography systems as well as the successful off-column formation of diastereomeric complexes have expanded the selectivity profiles and application fields. All of these issues are touched in the review, shedding light to the contributions appeared in the last decade.

Research paper thumbnail of 8.8 Chromatographic Separations and Analysis: Chiral Ion and Ligand Exchange Stationary Phases

Comprehensive Chirality, 2012

Chiral ligand-exchange chromatography was invented in the late 1960s to early 1970s by Davankov a... more Chiral ligand-exchange chromatography was invented in the late 1960s to early 1970s by Davankov and Rogozhin, and can be still considered as the elective choice for the direct enantioseparation of compounds with chelating moieties. Among the numerous chelating species that have been evaluated as chiral selectors in ligand-exchange chromatography, a major role is played by a group of amino acids including proline, hydroxyproline, cysteine, histidine, phenylalanine, valine, lysine, isoleucine, penicillamine, and a few amino alcohols carrying a phenylglycinol or a leucinol residual as the basic scaffold.

Research paper thumbnail of Editorial: Chromatographic Enantioseparations in Pharmaceutical Analysis: From the Analytical to the Preparative-Scale

Current medicinal chemistry, 2017

Research paper thumbnail of Electrostatic attraction-repulsion model with Cinchona alkaloid-based zwitterionic chiral stationary phases exemplified for zwitterionic analytes

Analytica Chimica Acta, 2019

h i g h l i g h t s g r a p h i c a l a b s t r a c t ZWIX ® CSPs allow enantioseparations withou... more h i g h l i g h t s g r a p h i c a l a b s t r a c t ZWIX ® CSPs allow enantioseparations without displacer counter-ions in the eluent. The IMCI effect is sufficient to modulate the retention of ionizable compounds. An electrostatically driven "attraction-repulsion model" explains analyte retention.

Research paper thumbnail of Mechanistic investigations on a ligand-exchange system operatine with a chiral mobile phase

Pleural cavity is covered by two screens: visceral pleural that covered lung and the parietal ple... more Pleural cavity is covered by two screens: visceral pleural that covered lung and the parietal pleura covering the chest wall and diaphragm. Liquid and protein entered to this space in normal mode via the systemic circulation and absorbed by the lymphatic vessels of parietal pleura. Pleural pressure lower than atmospheric pressure and this cause the lungs to inflate. Because of permeable nature of mesothelial cells layer, extra fluids can enter to this low pressure and wide space. Therefore, the pleuraleffusions are common and havedifferent causes. These accumulations can caused by pleural diseases or pectoral and ventral organs. Its annual incidence is about 1.5 million in US. One third of them come from heart failure.

Research paper thumbnail of Original enantioseparation of illicit fentanyls with cellulose-based chiral stationary phases under polar-ionic conditions

Journal of Chromatography A, 2021

Fentanyl analogues used in therapy and a range of highly potent non-pharmaceutical fentanyl deriv... more Fentanyl analogues used in therapy and a range of highly potent non-pharmaceutical fentanyl derivatives are subject to international control, as the latter are increasingly being synthesized illicitly and sold as 'synthetic heroin', or mixed with heroin. A significant number of hospitalizations and deaths have been reported in the EU and USA following the use of illicitly synthesized fentanyl derivatives. It has been unequivocally demonstrated that the enantiomers of fentanyl derivatives exhibit different pharmaco-toxicological profiles, which makes crucial to avail of suitable analytical methods enabling investigations at a "stereochemical level". Chromatographic methods useful to discriminate the enantioseparation of fentanyls and their derivatives are still missing in the literature. This is the first study in which the enantioseparation of four fentanyl derivatives, that is, (±)-trans-3-methyl norfentanyl, (±)-cis-3-methyl norfentanyl, β-hydroxyfentanyl, and β-hydroxythiofentanyl, has been obtained under polar-ionic conditions. Indeed, the use of ACN-based mobile phases with minor amounts of either 2-propanol or ethanol (plus diethylamine and formic acid as ionic additives) allowed obtaining enantioseparation and enantioresolution factors up to 1.83 and 7.02, respectively. For the study, the two chiral stationary phases cellulose tris(3-chloro-4-methylphenylcarbamate) and cellulose tris(4-chloro-3-methylphenylcarbamate) were used, displaying a remarkably different performance towards the enantioseparation of (±)-cis-3-methyl norfentanyl. Chiral LC analyses with a high-resolution mass spectrometry detector were also carried out in order to confirm the obtained data and demonstrate the suitability and compatibility of the optimized mobile phases with mass spectrometric systems.

Research paper thumbnail of Effective and Selective Extraction of Quercetin from Onion (Allium cepa L.) Skin Waste Using Water Dilutions of Acid-Based Deep Eutectic Solvents

Materials, 2021

Deep Eutectic Solvents (DESs) are experiencing growing interest as substitutes of polluting organ... more Deep Eutectic Solvents (DESs) are experiencing growing interest as substitutes of polluting organic solvents for their low or absent toxicity and volatility. Moreover, they can be formed with natural bioavailable and biodegradable molecules; they are synthesized in absence of hazardous solvents. DESs are, inter alia, successfully used for the extraction/preconcentration of biofunctional molecules from complex vegetal matrices. Onion skin is a highly abundant waste material which represents a reservoir of molecules endowed with valuable biological properties such as quercetin and its glycosylated forms. An efficient extraction of these molecules from dry onion skin from “Dorata di Parma” cultivar was obtained with water dilution of acid-based DESs. Glycolic acid (with betaine 2/1 molar ratio and L-Proline 3/1 molar ratio as counterparts) and of p-toluensulphonic acid (with benzyltrimethylammonium methanesulfonate 1/1 molar ratio)-based DESs exhibited more than 3-fold higher extractio...

Research paper thumbnail of Fragment based drug design and diversity-oriented synthesis of carboxylic acid isosteres

Bioorganic & Medicinal Chemistry, 2020

The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid repl... more The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid replacement. However, systematic assessment of acid surrogates is often time consuming and expensive, while prediction of both physicochemical properties (logP and logD) as well as acidity would be desirable at early discovery stages for a better analog design. Herein in this work, to enable decision making on a project, we have synthesized by employing a Diversity-Oriented Synthetic (DOS) methodology, a small library of molecular fragments endowed with acidic properties. By combining in-silico and experimental methodologies these compounds were chemically characterized and, particularly, with the aim to know their physicochemical properties, the aqueous ionization constants (pKa), partition coefficients logD and logP of each fragment was firstly estimated by using molecular modeling studies and then validated by experimental determinations. A face to face comparison between data and the corresponding carboxylic acid might help medicinal chemists in finding the best replacement to be used. Finally, in the framework of Fragment Based Drug Design (FBDD) the small library of fragments obtained with our approach showed good versatility both in synthetic and physico-chemical properties.

Research paper thumbnail of Exploiting Food-Grade Mesoporous Silica to Preserve the Antioxidant Properties of Fresh Olive Mill Wastewaters Phenolic Extracts

Antioxidants, 2021

Fresh olive mill wastewaters phenolic extracts are of great interest as preservatives or fortifyi... more Fresh olive mill wastewaters phenolic extracts are of great interest as preservatives or fortifying ingredients but are characterized by limited stability. The purpose of this study was to use mesoporous silica to enhance their stability and preserve their antioxidant properties. The phenolic extracts were characterized for their composition by HPLC-DAD and included in a mesoporous matrix with or without a lipid coating. The inclusion complexes were characterized in terms of total phenolic content, radical scavenging capacity and in vitro antioxidative activity and cell compatibility. Besides, inclusion complex stability under different storage conditions (22 and 37 °C, 75% relative humidity, 1 month) was evaluated. The inclusion process was nearly quantitative and modified neither the total phenolic content nor the total antioxidant capacity. None of the inclusion complex concentrations assayed on the HT29 cell line showed toxicity. Moreover, HT29 cells treated with the inclusion c...

Research paper thumbnail of Improved chromatographic diastereoresolution of cyclopropyl dafachronic acid derivatives using chiral anion exchangers

Journal of Chromatography A, Jul 1, 2018

Research paper thumbnail of Effect of Cocoa Roasting on Chocolate Polyphenols Evolution

Antioxidants

Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood fl... more Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood flow improvement or blood pressure and glycemia reduction, as well as cognitive function improvement. Unfortunately, polyphenol content is reduced during cocoa fermentation, drying, roasting and all the other phases involved in the chocolate production. Here, we investigated the evolution of the polyphenol content during all the different steps of chocolate production, with a special emphasis on roasting (3 different roasting cycles with 80, 100, and 130 °C as maximum temperature). Samples were followed throughout all processes by evaluating the total polyphenols content, the antioxidant power, the epicatechin content, and epicatechin mean degree of polymerization (phloroglucinol adducts method). Results showed a similar trend for total polyphenol content and antioxidant power with an unexpected bell-shaped curve: an increase followed by a decrease for the three different roasting temperat...

Research paper thumbnail of Multiple Heart-Cutting Two-Dimensional HPLC-UV Achiral–Chiral Analysis of Branched-Chain Amino Acids in Food Supplements under Environmentally Friendly Conditions

Separations

A multiple heart-cutting (mLC-LC) two-dimensional HPLC-UV achiral–chiral method for the direct an... more A multiple heart-cutting (mLC-LC) two-dimensional HPLC-UV achiral–chiral method for the direct analysis of branched-chain amino acids (BCAAs) in food supplements under environmentally friendly conditions was developed to cope with the very well-known limited chemoselectivity of chromatographic media for enantioselective analysis. Both achiral and chiral methods were developed in compliance with the main principles of green chromatography. The achiral analysis was performed isocratically with an optimized ion-pair reversed-phase (IP-RP) method based on a water/EtOH (95:5, v/v) mobile phase containing heptafluorobutyric acid (7 mM) as the IP agent. The achiral method was characterized by a very appreciable performance and was validated before the analysis of the real sample. High recovery values for all compounds (from 97% to 101%) were found in the interday evaluation. Additionally, low RSD% values in the long-term period were measured, in the range between 1.1% and 4.8%. Still, an L...

Research paper thumbnail of Combining molecular modeling approaches to establish the chromatographic enantiomer elution order in the absence of pure enantiomeric standards: A study case with two tetracyclic quinolines

Research paper thumbnail of Separation and determination of cysteine enantiomers in plasma after derivatization with 4-fluoro-7-nitrobenzofurazan

Journal of Pharmaceutical and Biomedical Analysis, 2022

The importance of D-amino acids in mammals associated with enantio-dependent biological functions... more The importance of D-amino acids in mammals associated with enantio-dependent biological functions has been increasingly highlighted. In addition to naturally occurring, D-amino acid supplementation could have a positive biological impact, including cytoprotective implications. In this context, supplementation with D-cysteine has revealed beneficial effects. Quantification of cysteine enantiomers in rodent plasma has been achieved by using 4-fluoro-7-nitrobenzofurazan derivatization of the target analytes. Cystine, the main form of cysteine in the plasma, was initially reduced to cysteine using DL-dithiothreitol. Baseline enantioseparation was then achieved in less than 3 min using a (R,R)-Whelk-O 1 stationary phase and isocratic elution using CH3OH-H2O 90:10 (v/v) with 15 mM ammonium formate (apparent pH 6.0) at 0.5 mL/min. The derivatives were then detected using negative ESI-MS in SRM mode. An external calibration was employed for D-cysteine, while L-cysteine quantification, as an endogenous analyte, was addressed using a background subtraction strategy. The method was validated. Response functions were obtained from 0 to 300 µM and from 0 to 125 µM for D-cysteine and L-cysteine, respectively. The trueness ranged from 96% to 105% for both enantiomers with repeatability and intermediate precision lower than 8% and 15% for the D-form and the endogenous L-form, respectively. The method was successfully applied for determining D- and L-cysteine in mouse plasma after D-cysteine administration.

Research paper thumbnail of Short Communication (S)-(-)-a,a-Di(2-naphthyl)-2-pyrrolidinemethanol, a useful tool to study the recognition mechanism in chiral ligand-exchange chromatography

Research paper thumbnail of Use of a Zwitterionic Surfactant to Improve the Biofunctional Properties of Wool Dyed with an Onion (Allium cepa L.) Skin Extract

Antioxidants, 2020

To improve the loadability and antioxidant properties of wool impregnated with onion skin extract... more To improve the loadability and antioxidant properties of wool impregnated with onion skin extract, the introduction of SB3-14 surfactant in the dyeing process was evaluated. A preliminary investigation on the surfactant–quercetin interaction indicated that the optimal conditions for dye solubility, stability, and surfactant affinity require double-distilled water (pH = 5.5) as a medium and SB3-14 in a concentration above the c.m.c. (2.5 × 10−3 M). The absorption profile of textiles showed the flavonoid absorption band (390 nm) and a bathochromic feature (510 nm), suggesting flavonoid aggregates. The higher absorbance for the sample dyed with SB3-14 indicated greater dye uptake, which was further confirmed by HPLC analysis. The Folin–Ciocalteu method was applied to evaluate the total phenol content (TPC) released from the treated wool, while the assays FRAP, DPPH, ABTS, and ORAC were applied to evaluate the corresponding total antioxidant activity (TAC). Higher TPCs (about 20%) and T...

Research paper thumbnail of Antioxidant Power on Dermal Cells by Textiles Dyed with an Onion (Allium cepa L.) Skin Extract

Antioxidants, 2021

In this study, the phenol loading and antioxidant activity of wool yarn prepared with the aqueous... more In this study, the phenol loading and antioxidant activity of wool yarn prepared with the aqueous extract of onion (Allium cepa L.) skin was enhanced by implementing the dyeing process with the use of alum as a mordant. Spectrophotometric and chromatographic methods were applied for the characterization of polyphenolic substances loaded on the wool yarn. The antioxidant/anti-inflammatory properties were evaluated by determining the level of intra- and extra-cellular reactive oxygen species (ROS) production in keratinocytes and dermal fibroblasts pre-treated with lipopolysaccharide put in contact with artificial sweat. An elevated dye uptake on wool was observed for the pre-mordanted sample, as demonstrated by high absorbance values in the UV-Visible spectral range. Chromatographic results showed that protocatechuic acid and its glucoside were the main phenolic acid released in artificial sweat by the wool yarns, while quercetin-4′-glucoside and its aglycone quercetin were more retai...

Research paper thumbnail of Laboratory-Scale Semipreparative Enantioresolution of Phenylethanolic-Azole Heme Oxygenase-1 Inhibitors

Chromatographia, 2020

In the present work, the development and application of two HPLC methods enabling the semiprepara... more In the present work, the development and application of two HPLC methods enabling the semipreparative enantioresolution of 1-(biphenyl-3-yl)-2-(1H-imidazol-1-yl)ethanol (1) and 1-[4-[(4-bromobenzyl)oxy]phenyl]-2-(1H-imidazol-1-yl)ethanol (2), two among the most potent and selective heme oxygenase-1 (HO-1) inhibitors known, are described. During the optimization step, different chiral stationary phase (CSP) features were evaluated, especially focusing the attention on (1) the type (electron-donating and electron-withdrawing) and position of the substituents in the phenyl moiety; (2) the physical coating or covalent immobilization of the modified polymer chain. Additionally, the effect of different types and amount of alcohol in the normal-phase eluent as well as of the column temperature, were investigated. For compound 1, Lux Cellulose-1 CSP containing cellulose tris(3,5-dimethylphenylcarbamate) was identified as the optimal choice in combination with a mobile phase consisting of n-hexane/ethanol-85/15 (v/v). Conversely, for compound 2, Lux Cellulose-2 CSP containing the cellulose tris(3-chloro-4-methyl phenylcarbamate)-based chiral selector was identified as the optimal choice, running the analysis with a n-hexane/ethanol/2-propanol-80/15/5 (v/v/v) mobile phase.

Research paper thumbnail of Optimized one-pot derivatization and enantioseparation of cysteine: Application to the study of a dietary supplement

Journal of Pharmaceutical and Biomedical Analysis, 2020

Cysteine is a sulfur-containing amino acid which plays an outstanding role in many biological pat... more Cysteine is a sulfur-containing amino acid which plays an outstanding role in many biological pathways in mammals. The analysis and quantification of native cysteine remains a critical issue due to its highly reactive thiol group evolving to the disulfide cystine derivative through oxidation reaction. Aimed at improving the derivative stability, cysteine was labelled with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), which reacts with both amino and thiol groups. The derivatization was optimized and the chemical identity of the reaction product was assessed via high-resolution mass spectrometry. The NBD-cysteine derivative resulted stable for 10 days. This derivative was enantioresolved (α and RS equal to 1.25 and 2.70, respectively) thanks to a (R,R)-Whelk-O1 phase with the following chromatographic setting: eluent, MeOH/water-90/10 (v/v) with 15 mM ammonium formate (pwsH 6.0); column temperature, 35 °C; flow rate, 1.0 mL/min. The developed method was validated following the ICH guidelines and applied for the quality control of a L-cysteine containing dietary supplement.

Research paper thumbnail of Enantioselective high-performance liquid chromatography analysis of oxygenated polyunsaturated fatty acids

Free Radical Biology and Medicine, 2019

Oxygenated polyunsaturated fatty acids (PUFAs)play an outstanding role in the physiological and p... more Oxygenated polyunsaturated fatty acids (PUFAs)play an outstanding role in the physiological and pathological regulation of several biological processes. These oxygenated metabolites can be produced both enzimatically, yielding almost pure enantiomers, and non-enzymatically. The free radical-mediated non-enzymatic oxidation commonly produces racemic mixtures which are used as biomarkers of oxidative stress and tissue damage. The biological activity of oxygenated PUFAs is often associated with only one enantiomer, making it necessary of availing of lipidomics platforms allowing to disclose the role of single enantiomers in health and disease. Polysaccharide-based chiral stationary phases (CSPs) play a dominating part in this setting. As for the cellulose backbone, 4-methylbenzoate derivatives exhibit very high chiral recognition ability towards this class of compounds. Concerning the phenylcarbamate derivatives of cellulose and amylose, the tris(3,5-dimethylphenylcarbamate) variants show the best enantioresolving ability for a variety of oxygenated PUFAs. Moreover, also the amylose tris(5-chloro-2-methylphenylcarbamate)-based selector produces relevant chromatographic performances. The extreme versatility of those CSPs mostly depends on their compatibility with the most relevant elution modes: normal- and reversed-phase, as well as polar organic/ionic-mode. In this review article, a selection of enantioseparation studies of different oxygenated PUFAs is reported, with both tris(benzoates) and tris(phenylcarbamates) of cellulose and amylose.

Research paper thumbnail of Last ten years (2008-2018) of chiral ligand-exchange chromatography in HPLC: An updated review

Journal of Separation Science, 2018

Chiral ligand-exchange chromatography is one of the elective strategies for the direct enantiores... more Chiral ligand-exchange chromatography is one of the elective strategies for the direct enantioresolution of small chelating compounds: amino acids, diamines, amino alcohols, diols, small peptides, etc. Unlike other methods, the interaction between chiral selector and analyte enantiomers is mediated by a cation, thus producing diastereomeric ternary complexes. Two main approaches are conventionally applied in chiral ligand-exchange chromatography. The first relies upon chiral stationary phases where the chiral selector is either covalently immobilized or physically adsorbed onto suitable packing materials (coated phases). In the second approach, chiral molecules are added to the eluent, thus generating chiral eluent systems. Among the advantages of chiral ligand-exchange chromatography, the generation of UV/vis-active metal complexes, and the use of commercially available or easy-to-synthesize chiral selectors, in combination to rather inexpensive achiral columns for coated phases and chiral eluents, are noteworthy. Besides amino acids and amino alcohols, other species have proven suitable for chiral ligand-exchange chromatography applications. Recently, the use of either chiral ionic liquids or micellar liquid chromatography systems as well as the successful off-column formation of diastereomeric complexes have expanded the selectivity profiles and application fields. All of these issues are touched in the review, shedding light to the contributions appeared in the last decade.

Research paper thumbnail of 8.8 Chromatographic Separations and Analysis: Chiral Ion and Ligand Exchange Stationary Phases

Comprehensive Chirality, 2012

Chiral ligand-exchange chromatography was invented in the late 1960s to early 1970s by Davankov a... more Chiral ligand-exchange chromatography was invented in the late 1960s to early 1970s by Davankov and Rogozhin, and can be still considered as the elective choice for the direct enantioseparation of compounds with chelating moieties. Among the numerous chelating species that have been evaluated as chiral selectors in ligand-exchange chromatography, a major role is played by a group of amino acids including proline, hydroxyproline, cysteine, histidine, phenylalanine, valine, lysine, isoleucine, penicillamine, and a few amino alcohols carrying a phenylglycinol or a leucinol residual as the basic scaffold.

Research paper thumbnail of Editorial: Chromatographic Enantioseparations in Pharmaceutical Analysis: From the Analytical to the Preparative-Scale

Current medicinal chemistry, 2017

Research paper thumbnail of Electrostatic attraction-repulsion model with Cinchona alkaloid-based zwitterionic chiral stationary phases exemplified for zwitterionic analytes

Analytica Chimica Acta, 2019

h i g h l i g h t s g r a p h i c a l a b s t r a c t ZWIX ® CSPs allow enantioseparations withou... more h i g h l i g h t s g r a p h i c a l a b s t r a c t ZWIX ® CSPs allow enantioseparations without displacer counter-ions in the eluent. The IMCI effect is sufficient to modulate the retention of ionizable compounds. An electrostatically driven "attraction-repulsion model" explains analyte retention.

Research paper thumbnail of Mechanistic investigations on a ligand-exchange system operatine with a chiral mobile phase

Pleural cavity is covered by two screens: visceral pleural that covered lung and the parietal ple... more Pleural cavity is covered by two screens: visceral pleural that covered lung and the parietal pleura covering the chest wall and diaphragm. Liquid and protein entered to this space in normal mode via the systemic circulation and absorbed by the lymphatic vessels of parietal pleura. Pleural pressure lower than atmospheric pressure and this cause the lungs to inflate. Because of permeable nature of mesothelial cells layer, extra fluids can enter to this low pressure and wide space. Therefore, the pleuraleffusions are common and havedifferent causes. These accumulations can caused by pleural diseases or pectoral and ventral organs. Its annual incidence is about 1.5 million in US. One third of them come from heart failure.

Research paper thumbnail of Original enantioseparation of illicit fentanyls with cellulose-based chiral stationary phases under polar-ionic conditions

Journal of Chromatography A, 2021

Fentanyl analogues used in therapy and a range of highly potent non-pharmaceutical fentanyl deriv... more Fentanyl analogues used in therapy and a range of highly potent non-pharmaceutical fentanyl derivatives are subject to international control, as the latter are increasingly being synthesized illicitly and sold as 'synthetic heroin', or mixed with heroin. A significant number of hospitalizations and deaths have been reported in the EU and USA following the use of illicitly synthesized fentanyl derivatives. It has been unequivocally demonstrated that the enantiomers of fentanyl derivatives exhibit different pharmaco-toxicological profiles, which makes crucial to avail of suitable analytical methods enabling investigations at a "stereochemical level". Chromatographic methods useful to discriminate the enantioseparation of fentanyls and their derivatives are still missing in the literature. This is the first study in which the enantioseparation of four fentanyl derivatives, that is, (±)-trans-3-methyl norfentanyl, (±)-cis-3-methyl norfentanyl, β-hydroxyfentanyl, and β-hydroxythiofentanyl, has been obtained under polar-ionic conditions. Indeed, the use of ACN-based mobile phases with minor amounts of either 2-propanol or ethanol (plus diethylamine and formic acid as ionic additives) allowed obtaining enantioseparation and enantioresolution factors up to 1.83 and 7.02, respectively. For the study, the two chiral stationary phases cellulose tris(3-chloro-4-methylphenylcarbamate) and cellulose tris(4-chloro-3-methylphenylcarbamate) were used, displaying a remarkably different performance towards the enantioseparation of (±)-cis-3-methyl norfentanyl. Chiral LC analyses with a high-resolution mass spectrometry detector were also carried out in order to confirm the obtained data and demonstrate the suitability and compatibility of the optimized mobile phases with mass spectrometric systems.

Research paper thumbnail of Effective and Selective Extraction of Quercetin from Onion (Allium cepa L.) Skin Waste Using Water Dilutions of Acid-Based Deep Eutectic Solvents

Materials, 2021

Deep Eutectic Solvents (DESs) are experiencing growing interest as substitutes of polluting organ... more Deep Eutectic Solvents (DESs) are experiencing growing interest as substitutes of polluting organic solvents for their low or absent toxicity and volatility. Moreover, they can be formed with natural bioavailable and biodegradable molecules; they are synthesized in absence of hazardous solvents. DESs are, inter alia, successfully used for the extraction/preconcentration of biofunctional molecules from complex vegetal matrices. Onion skin is a highly abundant waste material which represents a reservoir of molecules endowed with valuable biological properties such as quercetin and its glycosylated forms. An efficient extraction of these molecules from dry onion skin from “Dorata di Parma” cultivar was obtained with water dilution of acid-based DESs. Glycolic acid (with betaine 2/1 molar ratio and L-Proline 3/1 molar ratio as counterparts) and of p-toluensulphonic acid (with benzyltrimethylammonium methanesulfonate 1/1 molar ratio)-based DESs exhibited more than 3-fold higher extractio...

Research paper thumbnail of Fragment based drug design and diversity-oriented synthesis of carboxylic acid isosteres

Bioorganic & Medicinal Chemistry, 2020

The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid repl... more The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid replacement. However, systematic assessment of acid surrogates is often time consuming and expensive, while prediction of both physicochemical properties (logP and logD) as well as acidity would be desirable at early discovery stages for a better analog design. Herein in this work, to enable decision making on a project, we have synthesized by employing a Diversity-Oriented Synthetic (DOS) methodology, a small library of molecular fragments endowed with acidic properties. By combining in-silico and experimental methodologies these compounds were chemically characterized and, particularly, with the aim to know their physicochemical properties, the aqueous ionization constants (pKa), partition coefficients logD and logP of each fragment was firstly estimated by using molecular modeling studies and then validated by experimental determinations. A face to face comparison between data and the corresponding carboxylic acid might help medicinal chemists in finding the best replacement to be used. Finally, in the framework of Fragment Based Drug Design (FBDD) the small library of fragments obtained with our approach showed good versatility both in synthetic and physico-chemical properties.

Research paper thumbnail of Exploiting Food-Grade Mesoporous Silica to Preserve the Antioxidant Properties of Fresh Olive Mill Wastewaters Phenolic Extracts

Antioxidants, 2021

Fresh olive mill wastewaters phenolic extracts are of great interest as preservatives or fortifyi... more Fresh olive mill wastewaters phenolic extracts are of great interest as preservatives or fortifying ingredients but are characterized by limited stability. The purpose of this study was to use mesoporous silica to enhance their stability and preserve their antioxidant properties. The phenolic extracts were characterized for their composition by HPLC-DAD and included in a mesoporous matrix with or without a lipid coating. The inclusion complexes were characterized in terms of total phenolic content, radical scavenging capacity and in vitro antioxidative activity and cell compatibility. Besides, inclusion complex stability under different storage conditions (22 and 37 °C, 75% relative humidity, 1 month) was evaluated. The inclusion process was nearly quantitative and modified neither the total phenolic content nor the total antioxidant capacity. None of the inclusion complex concentrations assayed on the HT29 cell line showed toxicity. Moreover, HT29 cells treated with the inclusion c...