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Authors = Claudio Villani

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11 pages, 874 KiB  
Article
Low Tidal Volume Ventilation in Percutaneous Liver Ablations: Preliminary Experience on 10 Patients
by Francesco Giurazza, Francesco Coletta, Antonio Tomasello, Fabio Corvino, Silvio Canciello, Claudio Carrubba, Vincenzo Schettini, Francesca Schettino, Romolo Villani and Raffaella Niola
Diagnostics 2025, 15(12), 1495; https://doi.org/10.3390/diagnostics15121495 - 12 Jun 2025
Viewed by 402
Abstract
Objectives: Low tidal volume ventilation (LTVV) is a ventilatory strategy with the advantages of minimizing diaphragm movements and reducing hypercapnia and barotrauma risks. This preliminary study aims to report on the safety and effectiveness of LTVV applied during percutaneous US-guided liver ablations of [...] Read more.
Objectives: Low tidal volume ventilation (LTVV) is a ventilatory strategy with the advantages of minimizing diaphragm movements and reducing hypercapnia and barotrauma risks. This preliminary study aims to report on the safety and effectiveness of LTVV applied during percutaneous US-guided liver ablations of focal malignancies. Methods: Patients affected by focal liver malignancies treated with percutaneous microwaves ablation were retrospectively included in this single-center analysis. Arterial gas analysis was performed immediately before and after ablation to evaluate the arterial pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), and plasma lactate levels. The primary endpoint of this study was to evaluate the safety and efficacy of LTVV during percutaneous liver cancer ablation. The secondary endpoint was to assess the procedural technical success in terms of correct needle probe targeting without the need for repositioning. Results: Ten patients affected by a single liver lesion had been analyzed. The ASA score was three in all patients, with three patients also suffering from COPD. The procedural technical success was 100%: ablations were performed with a single liver puncture without the need for changing access or repositioning the needle. No variations in post-ablation arterial gas analysis requiring anesthesiological management remodulation occurred. Lactate levels remained stable and hemodynamic balance was preserved during all procedures. No switch to standard volume ventilation was required. Conclusions: In this preliminary study, LTVV was a safe and effective anesthesiological protocol in patients treated with percutaneous ablations of liver malignancies, offering an ideal balance between patient safety and percutaneous needle probe positioning precision. Larger prospective studies are needed to confirm these findings. Full article
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10 pages, 1496 KiB  
Article
Isolation and Chemotaxonomic Implications of Tenelloside, a Novel Unusual C-Glycosyl Flavanone from Phyllanthus tenellus Roxb. in Tenerife Island
by Antonio Francioso, Ignacio Antonio Jiménez Díaz, Carolina Pérez Reyes, Cristina González Montelongo, Marco Pierini, Claudio Villani and Isabel López Bazzocchi
Separations 2024, 11(1), 15; https://doi.org/10.3390/separations11010015 - 31 Dec 2023
Viewed by 2316
Abstract
Phyllanthus is a large genus of the Euphorbiaceae family, which has been widely used in traditional medicine. The current study reports the isolation of an unusual C-glycosyl flavonoid, named tenelloside, from Phyllanthus tenellus Roxb., a non-endemic plant present in Canary Islands. The [...] Read more.
Phyllanthus is a large genus of the Euphorbiaceae family, which has been widely used in traditional medicine. The current study reports the isolation of an unusual C-glycosyl flavonoid, named tenelloside, from Phyllanthus tenellus Roxb., a non-endemic plant present in Canary Islands. The chemical structure of this secondary metabolite was established employing combined spectrometric and spectroscopic techniques, including 1D and 2D NMR experiments and mass spectrometry. The absolute stereochemical configuration was determined via the comparison of experimental and calculated electronic circular dichroism spectra. In our previous work, another C-glycosylated bioactive product was isolated from another Phyllanthus species, suggesting that this class of compounds can be produced in a genus-specific manner in different geographic regions. This work represents another important report for direct future studies on the biological and chemotaxonomic potential of C-glycosylated products of the Phyllanthus genus. Full article
(This article belongs to the Special Issue Novel Applications of Separation Technology)
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14 pages, 1276 KiB  
Article
Understanding Factors Contributing to Vaccine Hesitancy in a Large Metropolitan Area
by Paolo Montuori, Immanuela Gentile, Claudio Fiorilla, Michele Sorrentino, Benedetto Schiavone, Valerio Fattore, Fabio Coscetta, Alessandra Riccardi, Antonio Villani, Ugo Trama, Francesca Pennino, Maria Triassi and Antonio Nardone
Vaccines 2023, 11(10), 1558; https://doi.org/10.3390/vaccines11101558 - 2 Oct 2023
Cited by 12 | Viewed by 3560
Abstract
Vaccine hesitancy has become a major global concern, leading to a significant decrease in the vaccination rate, with the World Health Organization recognizing it as one of the top ten threats to public health. Moreover, the health cost generated is evaluated to be [...] Read more.
Vaccine hesitancy has become a major global concern, leading to a significant decrease in the vaccination rate, with the World Health Organization recognizing it as one of the top ten threats to public health. Moreover, the health cost generated is evaluated to be 27 billion dollars per year in the US alone. To investigate the association between demographic variables and knowledge, attitudes, and behaviours related to vaccination, a survey-based cross-sectional study was conducted with 1163 individuals. Three models were used to perform a multiple linear regression analysis. In Model I, knowledge about vaccinations was found to be associated with smoking habits, education, and marital status. In Model II, attitudes towards vaccinations were significantly associated with sex, smoking habits, education, marital status, and knowledge. In Model III, behaviours related to vaccination were associated with sex, smoking habits, having children, knowledge, and attitudes. One potential solution to improve behaviours related to vaccinations in the general population is to implement specific public health programs, which can be a cost-effective intervention. This study provides valuable insights into the determinants of knowledge, attitudes, and behaviours related to vaccinations in the general population. Full article
(This article belongs to the Collection Factors Associated with Vaccine Hesitancy)
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10 pages, 1614 KiB  
Article
A New C2-Symmetric Atropisomeric Thiophene-Based Monomer for Inherently Chiral Electroactive Materials: Synthesis, HPLC Resolution, and Absolute Configuration Assignment
by Alessia Rosetti, Giulio Apolloni, Claudio Villani, Tiziana Benincori and Roberto Cirilli
Appl. Sci. 2023, 13(3), 1407; https://doi.org/10.3390/app13031407 - 20 Jan 2023
Cited by 2 | Viewed by 1864
Abstract
Herein, we report on the synthesis and high-performance liquid chromatography (HPLC) resolution of a new atropisomeric C2-symmetry chiral monomer based on the 3,3′-bithiophene core, which was developed to produce novel, inherently oligomeric chiral electroactive materials. The analytical enantioseparation was optimized using [...] Read more.
Herein, we report on the synthesis and high-performance liquid chromatography (HPLC) resolution of a new atropisomeric C2-symmetry chiral monomer based on the 3,3′-bithiophene core, which was developed to produce novel, inherently oligomeric chiral electroactive materials. The analytical enantioseparation was optimized using the cellulose-type Chiralpak IB-3 column and a mixture of n-hexane–methanol–dichloromethane 90:5:5 (v/v/v) as the mobile phase. During the scale-up of the enantioseparation analytical conditions to a semipreparative level, remarkable deformations in the HPLC profile, such as peak splitting and plateau zones between enantiomeric peaks, were observed. We demonstrate the effects of sample diluent as they relate to distorted peak profiles, as well as provide experimental solutions to prevent the disturbing phenomenon. The optimized chromatographic conditions were exploited to collect milligram amounts of the enantiopure sample, which was submitted to chiroptical and stereochemical characterization studies. Full article
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12 pages, 635 KiB  
Article
Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: Real-World Experience from Italy (the REAL.IT Study)
by Andrea Di Lenarda, Gabriele Di Gesaro, Filippo Maria Sarullo, Daniela Miani, Mauro Driussi, Michele Correale, Claudio Bilato, Andrea Passantino, Erberto Carluccio, Alessandra Villani, Luca degli Esposti, Chiara d’Agostino, Elena Peruzzi, Simone Poli and Massimo Iacoviello
J. Clin. Med. 2023, 12(2), 699; https://doi.org/10.3390/jcm12020699 - 16 Jan 2023
Cited by 11 | Viewed by 4758
Abstract
Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study [...] Read more.
Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials. Full article
(This article belongs to the Special Issue Clinical Advances in Cardiomyopathies)
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8 pages, 12562 KiB  
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The Pitfall of Ganglioneuroblastoma-Nodular Diagnosis: Clinical and Imaging Considerations over a Rare Bifocal Sporadic Case
by Claudio Montante, Francesco Fabozzi, Maria Felicia Villani, Maria Luisa D’Andrea, Alessandra Stracuzzi, Gian Luigi Natali, Giada Del Baldo, Francesca Del Bufalo, Maria Carmen Garganese, Annalisa Serra, Paolo Tomà, Rita Alaggio, Sabina Vennarini, Giovanna Stefania Colafati, Angela Mastronuzzi and Maria Antonietta De Ioris
Diagnostics 2022, 12(12), 3221; https://doi.org/10.3390/diagnostics12123221 - 19 Dec 2022
Cited by 3 | Viewed by 2988
Abstract
Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN [...] Read more.
Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN can coexist in the same mass, leading to incorrect risk staging when only biopsy is performed. Herein, we describe a case of multifocal NT (thoracic and abdominal localization) occurring in a 4-year-old male. Different histological subtypes, namely GNBI and GNBN, were revealed in the two lesions. We focus on the difficulties of proper diagnosis and risk stratification, underlining the usefulness of several diagnostic tools for appropriate management and therapeutic choices. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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12 pages, 1853 KiB  
Article
Separation of Monosaccharide Anomers on Photo-Click Cysteine-Based Stationary Phase: The α/β Interconversion Process Studied by Dynamic Hydrophilic Liquid Chromatography
by Andrea Calcaterra, Simone Manetto, Fabio Buonsenso, Antonio Francioso, Marco Pierini and Claudio Villani
Separations 2022, 9(8), 203; https://doi.org/10.3390/separations9080203 - 5 Aug 2022
Cited by 3 | Viewed by 3023
Abstract
In High-Performance Liquid Chromatography (HPLC), the separation of reducing sugars can typically show three possible typologies of chromatographic profiles (i.e., single peak, two resolved peaks and two peaks interconnected by a plateau) due to the rate at which the relevant α/β anomers interconversion [...] Read more.
In High-Performance Liquid Chromatography (HPLC), the separation of reducing sugars can typically show three possible typologies of chromatographic profiles (i.e., single peak, two resolved peaks and two peaks interconnected by a plateau) due to the rate at which the relevant α/β anomers interconversion (anomerization) can take place in relation to their elution-time. By analyzing these chromatographic profiles, thermodynamic and kinetic properties of anomerization phenomenon can be extrapolated. In this work we studied the anomerization of some monosaccharides by using a recently developed photo-click cysteine-based stationary phase through dynamic hydrophilic interaction liquid chromatography (D-HILIC) conditions. In the 5–25 °C temperature range, the ΔG#α→β and ΔG#β→α barriers were found to achieve values within the interval 21.1/22.2 kcal/mol for glucose, with differences between α→β and β→α reactions of about 0.4 kcal/mol. For xylose, in the same temperature range, the ΔG#α→β and ΔG#β→α barriers are between 20.7 to 21.5 kcal/mol, with differences between α→β and β→α reactions of about 0.2 kcal/mol. The experimental data are in agreement with those reported in literature, confirming the this new stationary phase using HILIC conditions is a robust platform to measure kinetic and thermodynamic properties of the isomerization reaction. Full article
(This article belongs to the Section Chromatographic Separations)
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12 pages, 2587 KiB  
Article
Effect of Natural Deep Eutectic Solvents on trans-Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation
by Roberto Mattioli, Daniel Di Risola, Rodolfo Federico, Alessia Ciogli, Francesco Gasparrini, Claudio Villani, Mario Fontana, Anna Maggiore, Maria d’Erme, Luciana Mosca and Antonio Francioso
Molecules 2022, 27(7), 2348; https://doi.org/10.3390/molecules27072348 - 6 Apr 2022
Cited by 11 | Viewed by 3396
Abstract
trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a [...] Read more.
trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations. Full article
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18 pages, 2562 KiB  
Article
Synthesis, Stereochemical and Photophysical Properties of Functionalized Thiahelicenes
by Valentina Pelliccioli, Francesca Cardano, Giacomo Renno, Francesca Vasile, Claudia Graiff, Giuseppe Mazzeo, Andrea Fin, Giovanna Longhi, Sergio Abbate, Alessia Rosetti, Claudio Villani, Guido Viscardi, Emanuela Licandro and Silvia Cauteruccio
Catalysts 2022, 12(4), 366; https://doi.org/10.3390/catal12040366 - 23 Mar 2022
Cited by 7 | Viewed by 3725
Abstract
We report on the synthesis of a novel class of functionalized thia[6]helicenes and a thia[5]helicene, containing a benzothiophene unit and a second heteroatom embedded in the helix (i.e., nitrogen and oxygen) or a pyrene or a spirobifluorene moiety. These systems are obtained through [...] Read more.
We report on the synthesis of a novel class of functionalized thia[6]helicenes and a thia[5]helicene, containing a benzothiophene unit and a second heteroatom embedded in the helix (i.e., nitrogen and oxygen) or a pyrene or a spirobifluorene moiety. These systems are obtained through straightforward and general procedures that involve: (i) palladium-catalyzed annulation of iodo-atropoisomers with internal alkynes and (ii) Suzuki coupling of iodo-atropoisomers with phenyl boronic acid followed by a Mallory-type reaction. Both experimental and theoretical studies on the configurational stability of some selected thia[6]helicenes confirmed their stability toward racemization at room temperature, while the pyrene-based thia[5]helicene was found to be unstable. Moreover, the configuration assignment for one representative thiahelicene was established through the comparison between experimental and theoretical circular dichroism (CD) spectra. A systematic study of the photophysical properties of both thiahelicenes and the corresponding atropoisomers has been carried out to provide a complete overview on the new molecules proposed in this work. The obtained data showed regular trends in all the thiahelicene series with spectroscopic traits in line with those previously observed for similar heterohelicenes. Full article
(This article belongs to the Special Issue Catalysts for the Synthesis of Heterocyclic Compounds)
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19 pages, 356 KiB  
Article
Antimicrobial Prophylaxis in Neonates and Children Undergoing Dental, Maxillo-Facial or Ear-Nose-Throat (ENT) Surgery: A RAND/UCLA Appropriateness Method Consensus Study
by Erika Rigotti, Sonia Bianchini, Laura Nicoletti, Sara Monaco, Elena Carrara, Francesca Opri, Roberta Opri, Caterina Caminiti, Daniele Donà, Mario Giuffré, Alessandro Inserra, Laura Lancella, Alessandro Mugelli, Giorgio Piacentini, Nicola Principi, Simonetta Tesoro, Elisabetta Venturini, Annamaria Staiano, Alberto Villani, Enrico Sesenna, Claudio Vicini, Susanna Esposito and on behalf of the Peri-Operative Prophylaxis in Neonatal and Paediatric Age (POP-NeoPed) Study Groupadd Show full author list remove Hide full author list
Antibiotics 2022, 11(3), 382; https://doi.org/10.3390/antibiotics11030382 - 13 Mar 2022
Cited by 6 | Viewed by 5604
Abstract
Surgical site infections (SSIs) represent a potential complication in surgical procedures, mainly because clean/contaminated surgery involves organs that are normally colonized by bacteria. Dental, maxillo-facial and ear-nose-throat (ENT) surgeries are among those that carry a risk of SSIs because the mouth and the [...] Read more.
Surgical site infections (SSIs) represent a potential complication in surgical procedures, mainly because clean/contaminated surgery involves organs that are normally colonized by bacteria. Dental, maxillo-facial and ear-nose-throat (ENT) surgeries are among those that carry a risk of SSIs because the mouth and the first respiratory tracts are normally colonized by a bacterial flora. The aim of this consensus document was to provide clinicians with recommendations on surgical antimicrobial prophylaxis in neonates (<28 days of chronological age) and pediatric patients (within the age range of 29 days–18 years) undergoing dental, maxillo-facial or ENT surgical procedures. These included: (1) dental surgery; (2) maxilla-facial surgery following trauma with fracture; (3) temporo-mandibular surgery; (4) cleft palate and cleft lip repair; (5) ear surgery; (6) endoscopic paranasal cavity surgery and septoplasty; (7) clean head and neck surgery; (8) clean/contaminated head and neck surgery and (9) tonsillectomy and adenoidectomy. Due to the lack of pediatric data for the majority of dental, maxillo-facial and ENT surgeries and the fact that the recommendations for adults are currently used, there is a need for ad hoc studies to be rapidly planned for the most deficient areas. This seems even more urgent for interventions such as those involving the first airways since the different composition of the respiratory microbiota in children compared to adults implies the possibility that surgical antibiotic prophylaxis schemes that are ideal for adults may not be equally effective in children. Full article
(This article belongs to the Special Issue Antimicrobial Use in Pediatrics)
5 pages, 311 KiB  
Reply
Reply to Mirabelli et al. Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on “Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053”
by Silvia Damiana Visonà, Silvana Capella, Sofia Bodini, Paola Borrelli, Simona Villani, Eleonora Crespi, Andrea Frontini, Claudio Colosio, Ruggero Vigliaturo and Elena Belluso
Int. J. Environ. Res. Public Health 2021, 18(13), 7181; https://doi.org/10.3390/ijerph18137181 - 5 Jul 2021
Cited by 3 | Viewed by 2535
Abstract
We appreciate very much the interest of Mirabelli et al. [...] Full article
29 pages, 12471 KiB  
Article
Evaluating the Impact of a Wall-Type Green Infrastructure on PM10 and NOx Concentrations in an Urban Street Environment
by Maria Gabriella Villani, Felicita Russo, Mario Adani, Antonio Piersanti, Lina Vitali, Gianni Tinarelli, Luisella Ciancarella, Gabriele Zanini, Antonio Donateo, Matteo Rinaldi, Claudio Carbone, Stefano Decesari and Peter Sänger
Atmosphere 2021, 12(7), 839; https://doi.org/10.3390/atmos12070839 - 29 Jun 2021
Cited by 16 | Viewed by 5405
Abstract
Nature-based solutions can represent beneficial tools in the field of urban transformation for their contribution to important environmental services such as air quality improvement. To evaluate the impact on urban air pollution of a CityTree (CT), an innovative wall-type green infrastructure in passive [...] Read more.
Nature-based solutions can represent beneficial tools in the field of urban transformation for their contribution to important environmental services such as air quality improvement. To evaluate the impact on urban air pollution of a CityTree (CT), an innovative wall-type green infrastructure in passive (deposition) and active (filtration) modes of operation, a study was conducted in a real urban setting in Modena (Italy) during 2017 and 2018, combining experimental measurements with modelling system evaluations. In this work, relying on the computational resources of CRESCO (Computational Centre for Research on Complex Systems)/ENEAGRID High Performance Computing infrastructure, we used the air pollution microscale model PMSS (Parallel Micro-SWIFT-Micro SPRAY) to simulate air quality during the experimental campaigns. The spatial characteristics of the impact of the CT on local air pollutants concentrations, specifically nitrogen oxides (NOx) and particulate matter (PM10), were assessed. In particular, we used prescribed bulk deposition velocities provided by the experimental campaigns, which tested the CT both in passive (deposition) and in active (filtration) mode of operation. Our results showed that the PM10 and NOx concentration reductions reach from more than 0.1% up to about 0.8% within an area of 10 × 20 m2 around the infrastructure, when the green infrastructure operates in passive mode. In filtration mode the CT exhibited higher performances in the abatement of PM10 concentrations (between 1.5% and 15%), within approximately the same area. We conclude that CTs may find an application in air quality hotspots within specific urban settings (i.e., urban street canyons) where a very localized reduction of pollutants concentration during rush hours might be of interest to limit population exposure. The optimization of the spatial arrangement of CT modules to increment the “clean air zone” is a factor to be investigated in the ongoing development of the CT technology. Full article
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9 pages, 1880 KiB  
Article
Low Temperature Dynamic Chromatography for the Separation of the Interconverting Conformational Enantiomers of the Benzodiazepines Clonazolam, Flubromazolam, Diclazepam and Flurazepam
by Roberta Franzini, Alessia Rosetti and Claudio Villani
Symmetry 2021, 13(6), 1012; https://doi.org/10.3390/sym13061012 - 4 Jun 2021
Cited by 3 | Viewed by 2687
Abstract
Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction with the GABAa receptor in the central nervous system of mammals. BZDs are interesting both in clinical and forensic toxicology for their pharmacological characteristics [...] Read more.
Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction with the GABAa receptor in the central nervous system of mammals. BZDs are interesting both in clinical and forensic toxicology for their pharmacological characteristics and potential of abuse. The presence of a non-planar diazepine ring generates chiral conformational stereoisomers, even in the absence of stereogenic centers. A conformational enrichment of BZD at the binding sites has been reported in the literature, thus making interesting a stereodynamic screening of a wide range of BZDs. Herein, we report the investigation of three stereolabile 1,4-benzodiazepine included in the class of “designer benzodiazepines” (e.g., diclazepam, a chloro-derivative of diazepam, and two triazolo-benzodiazepines, flubromazolam and clonazolam) and a commercially available BZD known as flurazepam, in order to study the kinetic of the “ring-flip” process that allows two conformational enantiomers to interconvert at high rate at room temperature. A combination of low temperature enantioselective dynamic chromatography on chiral stationary phase and computer simulations of the experimental chromatograms allowed us to measure activation energies of enantiomerization (ΔG) lower than 18.5 kcal/mol. The differences between compounds have been correlated to the pattern of substitutions on the 1,4-benzodiazepinic core. Full article
(This article belongs to the Special Issue Chiral Molecules: Properties, Synthesis and Analysis)
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12 pages, 3078 KiB  
Review
Static vs. Dynamic Electrostatic Repulsion Reversed Phase Liquid Chromatography: Solutions for Pharmaceutical and Biopharmaceutical Basic Compounds
by Giulia Mazzoccanti, Francesco Gasparrini, Andrea Calcaterra, Claudio Villani and Alessia Ciogli
Separations 2021, 8(5), 59; https://doi.org/10.3390/separations8050059 - 2 May 2021
Cited by 6 | Viewed by 3397
Abstract
Many efforts have been made to separate basic compounds, which are challenging to resolve in reversed phase liquid chromatography. In this process, they are strongly retained and the peak shape undergoes significant distortion. The principal origin of this has been identified with the [...] Read more.
Many efforts have been made to separate basic compounds, which are challenging to resolve in reversed phase liquid chromatography. In this process, they are strongly retained and the peak shape undergoes significant distortion. The principal origin of this has been identified with the non-negligible interaction with residual deprotonated silanols. Consequently, all solutions that efficiently shield silanols are being sought. This review is an upgrade on the use of the electrostatic repulsion reversed phase (ERRP) approach: retention of bases, in protonated form, can be achieved by modulating the charge repulsion caused by the presence of positive charges in the chromatographic system. This study successfully (i) introduced fixed positive charges in the structure of stationary phases, (ii) used cationic and hydrophobic additives in the mobile phase, and (iii) used the ERRP-like approach employed at the preparative level for peptide purification. Full article
(This article belongs to the Section Analysis of Natural Products and Pharmaceuticals)
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11 pages, 2061 KiB  
Article
Comparison of Coated and Immobilized Chiral Stationary Phases Based on Amylose tris-[(S)-α-Methylbenzylcarbamate] for the HPLC Enantiomer Separation of α-Lipoic Acid and Its Reduced Form
by Alessia Rosetti, Claudio Villani, Marco Pierini and Roberto Cirilli
Molecules 2021, 26(6), 1747; https://doi.org/10.3390/molecules26061747 - 20 Mar 2021
Cited by 12 | Viewed by 2869
Abstract
The couple of chiral sulfur compounds α-lipoic acid (ALA)/α-dihydrolipoic acid (DHALA) has attracted considerable attention in recent years owing to its remarkable anti-inflammatory and antioxidant properties. It is well known that the chirality of the C6 plays a key role in determining the [...] Read more.
The couple of chiral sulfur compounds α-lipoic acid (ALA)/α-dihydrolipoic acid (DHALA) has attracted considerable attention in recent years owing to its remarkable anti-inflammatory and antioxidant properties. It is well known that the chirality of the C6 plays a key role in determining the biological activity of ALA. The natural occurring (R)-ALA enantiomer is an essential cofactor for key oxidative metabolism enzyme complexes and, after oral administration of the racemic mixture, it shows higher plasma concentration than (S)-ALA. Differently, the in vivo enantioselective action difference between the enantiomers of DHALA has not yet been studied. This lacking is perhaps due to the unavailability of analytical methods capable of determining the enantiomeric composition of biological samples during pharmacokinetic and pharmacodynamic events. In the present work, the direct and baseline enantioresolution of both chiral acids by HPLC on two amylose-derived chiral stationary phases is presented. The proposed chiral enantioselective protocol, therefore, does not require pre- or on-column derivatization. The performance of the coated Chiralpak AS-H CSP and the new immobilized Chiralpak IH-3 CSP, which have the same chiral selector amylose tris-[(S)-α-methylbenzylcarbamate], were compared using conventional normal-phase mobile phases containing ethanol or 2-propanol as alcoholic solvents and a fixed percentage of trifluoroacetic acid. Nonconventional eluents containing dichloromethane, ethyl acetate, and 2-methyltetrahydrofuran as organic cosolvents were applied in the separation of the enantiomers of two carboxylic acids on the immobilized Chiralpak IH-3 CSP. The effect of the column temperature was carefully evaluated in order to improve enantioselectivity. Adequate amounts of enantiomers were isolated by an analytical-size Chiralpak IH-3 column and submitted to chiroptical measurements. The absolute configuration assignment of the isolated enantiomers was determined by a multidisciplinary procedure based on the comparison of the experimental and calculated chiroptical properties. Full article
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