From speciation study to removal of Pb2+ from natural waters by a carnosine-based polyacrylamide/azlactone copolymer.

A deep speciation study on L-carnosine (CAR) and Pb2+ system was performed in aqueous solution with the aim to assess its potential use as a sequestering agent of metal cation. To determine the best conditions for Pb2+ complexation, potentiometric measurements were carried out over a wide range of ionic strength (0.15 ≤ I/≤ 1 mol/L) and temperature (15 ≤ T/°C ≤ 37), and thermodynamic interaction parameters (logß, ΔH, ΔG and TΔS) were determined. The speciation studies allowed us to simulate sequestration ability of CAR toward Pb2+ under different conditions of pH, ionic strength and temperature and to establish a priori the conditions for the best removal performance, i.e., pH > 7 and I = 001 mol/L. This preliminary investigation was very useful in optimizing removal procedures and limiting subsequent experimental measurements for adsorption tests. Therefore, to exploit the binding ability of CAR for Pb2+ removal from aqueous solutions, CAR was covalently grafted on an azlactone-activated beaded-polyacrylamide resin (AZ) using an efficient click coupling reaction (78.3% of coupling efficiency). The carnosine-based resin (AZCAR) was analyzed by ThermoGravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and Differential Thermal Analysis (DTA). Morphology, surface area and pore size distribution were studied through a combination of Scanning Electron Microscope (SEM) and adsorption/desorption of N2 analyses according to the Brunauer-Emmett-Teller (BET) and Barret-Johner-Halenda (BJH) approaches. The adsorption capacity of AZCAR toward Pb2+ was investigated under conditions simulating the ionic strength and pH of different natural waters. The time needed to reach equilibrium in the adsorption process was 24 h, and the best performance was obtained at pH > 7, typical of most natural waters, with removal efficiency ranging from 90.8% (at I = 0.7 mol/L) to 99.0 (at I = 0.001 mol/L).

Study on Metronidazole Acid-Base Behavior and Speciation with Ca2+ for Potential Applications in Natural Waters.

Metronidazole (MNZ) is an antibiotic widely used for the treatment of various infectious diseases and as an effective pesticide agent for the cultivation of chickens and fish. Its high resistance to purification processes and biological activity has led to the classification of MNZ as an emerging contaminant. A speciation study, aimed to define the acid-base properties of MNZ and its interaction with Ca2+, commonly present in natural waters, is reported. The protonation constants of MNZ, as well as the formation constant value of Ca2+-MNZ species, were obtained by potentiometric titrations in an aqueous solution, using NaCl as background salt at different ionic strengths (0.15, 0.5, 1 mol L-1) and temperature (15, 25 and 37 °C) conditions. The acid-base behavior and the complexation with Ca2+ were also investigated by 1H NMR and UV-Vis titrations, with results in very good agreement with the potentiometric ones. The dependence of the formation constants on the ionic strength and temperature was also determined. The sequestering ability of MNZ towards Ca2+ was defined by the empirical parameter pL0.5 at different pH and temperature values. The speciation of MNZ simulating sea water conditions was calculated.

Ab initio molecular dynamics simulations and experimental speciation study of levofloxacin under different pH conditions.

Levofloxacin is an extensively employed broad-spectrum antibiotic belonging to the fluoroquinolone class. Despite the extremely wide usage of levofloxacin for a plethora of diseases, the molecular characterization of this antibiotic appears quite poor in the literature. Moreover, the acid-base properties of levofloxacin - crucial for the design of efficient removal techniques from wastewaters - have never extensively been investigated so far. Here we report on a study on the behavior of levofloxacin under standard and diverse pH conditions in liquid water by synergistically employing static quantum-mechanical calculations along with experimental speciation studies. Furthermore, with the aim of characterizing the dynamics of the water solvation shells as well as the protonation and deprotonation mechanisms, here we present the unprecedented quantum-based simulation of levofloxacin in aqueous environments by means of state-of-the-art density-functional-theory-based molecular dynamics. This way, we prove the cooperative role played by the aqueous hydration shells in assisting the proton transfer events and, more importantly, the key place held by the nitrogen atom binding the methyl group of levofloxacin in accepting excess protons eventually present in water. Finally, we also quantify the energetic contribution associated with the presence of a H-bond internal to levofloxacin which, on the one hand, stabilizes the ground-state molecular structure of this antibiotic and, on the other, hinders the first deprotonation step of this fluoroquinolone. Among other things, the synergistic employment of quantum-based calculations and speciation experiments reported here paves the way toward the development of targeted removal approaches of drugs from wastewaters.

Oxazolidinone Antibiotics: Chemical, Biological and Analytical Aspects.

This review covers the main aspects concerning the chemistry, the biological activity and the analytical determination of oxazolidinones, the only new class of synthetic antibiotics advanced in clinical use over the past 50 years. They are characterized by a chemical structure including the oxazolidone ring with the S configuration of substituent at C5, the acylaminomethyl group linked to C5 and the N-aryl substituent. The synthesis of oxazolidinones has gained increasing interest due to their unique mechanism of action that assures high antibiotic efficiency and low susceptibility to resistance mechanisms. Here, the main features of oxazolidinone antibiotics licensed or under development, such as Linezolid, Sutezolid, Eperezolid, Radezolid, Contezolid, Posizolid, Tedizolid, Delpazolid and TBI-223, are discussed. As they are protein synthesis inhibitors active against a wide spectrum of multidrug-resistant Gram-positive bacteria, their biological activity is carefully analyzed, together with the drug delivery systems recently developed to overcome the poor oxazolidinone water solubility. Finally, the most employed analytical techniques for oxazolidinone determination in different matrices, such as biological fluids, tissues, drugs and natural waters, are reviewed. Most are based on HPLC (High Performance Liquid Chromatography) coupled with UV-Vis or mass spectrometer detectors, but, to a lesser extent are also based on spectrofluorimetry or voltammetry.

Removal of As(III) from Biological Fluids: Mono- versus Dithiolic Ligands.

Arsenic is one of the inorganic pollutants typically found in natural waters, and its toxic effects on the human body are currently of great concern. For this reason, the search for detoxifying agents that can be used in a so-called "chelation therapy" is of primary importance. However, to the aim of finding the thermodynamic behavior of efficient chelating agents, extensive speciation studies, capable of reproducing physiological conditions in terms of pH, temperature, and ionic strength, are in order. Here, we report on the acid-base properties of meso-2,3-dimercaptosuccinic acid (DMSA) at different temperatures (i.e., T = 288.15, 298.15, 310.15, and 318.15 K). In particular, its capability to interact with As(III) has been investigated by experimentally evaluating some crucial thermodynamic parameters (ΔH and TΔS), stability constants, and its speciation model. Additionally, in order to gather information on the microscopic coordination modalities of As(III) with the functional groups of DMSA and, at the same time, to better interpret the experimental results, a series of state-of-the-art ab initio molecular dynamics simulations have been performed. For the sake of completeness, the sequestering capabilities of DMSA-a simple dithiol ligand-toward As(III) are directly compared with those recently emerged from similar analyses reported on monothiol ligands.

Salinomycin-loaded PLA nanoparticles: drug quantification by GPC and wave voltammetry and biological studies on osteosarcoma cancer stem cells.

A new straightforward gel permeation chromatography (GPC) method was developed to calculate the drug encapsulation efficiency and loading content of Poly(lactic acid) nanoparticles (PLA NPs) loaded with Salinomycin (Sal), exploiting the capability of this technique to separate a macromolecular/molecular mixture on the basis of the molecular weight of each component. The proposed GPC method allowed Sal detection until 1% of Sal content in PLA NPs, avoiding sample pre-treatments. The method was validated by wave voltammetry (SW) technique, using a slightly modified literature procedure, useful to detect Sal in the concentration range 0.4 ≤ C/µmol/L ≤ 12 (linear concentration range). PLA-based NPs were prepared by nanoprecipitation with either native and functionalized PLA. Specifically, folate-decorated PLA NPs (PLA-FA NPs) were obtained by CuAAC click functionalization of alkyne-grafted PLA with azide-folate. Sal-loaded NPs were characterized physicochemically and morphologically. They exhibited adequate physicochemical properties, good drug encapsulation efficiency (98 ± 0.5% and 99 ± 0.5%), and loading content (8.8 ± 0.1% and 8.9 ± 0.1% for PLA/Sal and PLA-FA/Sal NPs, respectively). The size of empty PLA NPs resulted smaller (90 ± 3.2 nm and 680 ± 15.3 nm, for PLA NPs and PLA-FA NPs respectively) than the correspondent drug-loaded NPs (110 ± 3.8 nm and 875 ± 20.5 nm, respectively). Their biological activity was assessed on osteosarcoma bulk cells MG63, healthy osteoblast cell line (hFOB1.19), and enriched osteosarcoma cancer stem cells (CSCs), showing cell-depending effect. Entrapped Sal maintained its cytotoxic effect on CSCs and MG63 cells, with a potency comparable to the free drug and no evident benefit was detected for folate-decorated PLA NPs respect to native PLA NPs. Graphical abstract.

Interaction of Ampicillin and Amoxicillin with Mn2+: A Speciation Study in Aqueous Solution.

A potentiometric and UV spectrophotometric investigation on Mn2+-ampicillin and Mn2+-amoxicillin systems in NaCl aqueous solution is reported. The potentiometric measurements were carried out under different conditions of temperature (15 ≤ t/°C ≤ 37). The obtained speciation pattern includes two species for both the investigated systems. More in detail, for system containing ampicillin MLH and ML species, for that containing amoxicillin, MLH2 and MLH ones. The spectrophotometric findings have fully confirmed the results obtained by potentiometry for both the systems, in terms of speciation models as well as the stability constants of the formed species. Enthalpy change values were calculated via the dependence of formation constants of the species on temperature. The sequestering ability of ampicillin and amoxicillin towards Mn2+ was also evaluated under different conditions of pH and temperature via pL0.5 empirical parameter (i.e., cologarithm of the ligand concentration required to sequester 50% of the metal ion present in traces).

Complexation of As(III) by phosphonate ligands in aqueous fluids: Thermodynamic behavior, chemical binding forms and sequestering abilities.

In recent years, the contamination of water by arsenic reached alarming levels in many countries of the world, attracting the interest of many researchers engaged in testing methodologies able to remove this harmful pollutant. An important aspect that must be taken into consideration is the possibility to find arsenic in different chemical forms which could require different approaches for its removal. At this aim, a speciation analysis appears to be crucial for better understanding the behavior of arsenic species in aqueous solutions, especially in presence of compounds with marked chelating properties. Phosphonates can be identified as good sequestering agents and, at this purpose, this manuscript intends to investigate the interaction of As(III) with three phosphonic acids derived from nitrilotriacetic acid (NTA) by replacements of one (N-(Phosphonomethyl) iminodiacetic acid, NTAP), two (N,N-Bis-(phosphonomethyl) glycine, NTA2P) and three (Nitrilotri(methylphosphonic acid), NTA3P) carboxylic groups with the same number of phosphonate groups. An in-depth potentiometric and calorimetric investigation allowed to determine speciation models featured by simple ML, MLHi and ML(OH) species. A complete thermodynamic characterization of the systems is reported together with the definition of coordination mode by mass spectrometry measurements. On the light of the speciation models, the possibility of using these ligands in arsenic removal techniques was assessed by determining the pL0.5 (the concentration of ligand able to remove the 50% of metal ion present in trace). All ligands show a good sequestering ability, in particular under the conditions of fresh water, following the trend NTA3P > NTA2P > NTAP.

Stability of hydrolytic arsenic species in aqueous solutions: As3+vs. As5.

Notwithstanding the fact that arsenic compounds are ubiquitous in the As3+ and As5+ forms in aqueous solutions, most of the microscopic features underlying the conditions of the hydrolysis steps are completely unknown. This way, a first-principles description of the fundamental behaviour of common arsenic species in natural waters and biological fluids is still lacking. Here we report on a synergistic computational and experimental investigation on As3+ and As5+ speciation in aqueous solution under both standard and sizably different alkaline circumstances. If, on the one hand, ab initio molecular dynamics simulations have been used to microscopically trace the different hydrolysis steps of As3+ and As5+ by explicitly taking into account the solvent contribution, on the other hand, they have been able to identify - and predict - the most stable hydrolytic species. In addition, by means of potentiometric and calorimetric measurements, the thermodynamic parameters (log K, ΔH, and TΔS) have been determined at different ionic strength values (0 < I ≤ 1 mol L-1). By comparing the computational and the experimental findings of the species distribution under conditions of some biological fluids, a qualitative agreement on the compounds formed by As3+ and As5+ is thoroughly recorded and, therefore, the stable hydrolytic arsenic species present in natural waters and other biosystems are fully characterised.

Experimental and computational study on morin and its complexes with Mg2+, Mn2+, Zn2+, and Al3+: Coordination and antioxidant properties.

Morin (MRN), an intriguing bioflavonol, has received increasing interest for its antioxidant properties, as have its metal complexes (Mz+-MRN). Understanding their antioxidant behavior is critical to assess their pharmaceutical, nutraceutical potential, and therapeutic impact in the design of advanced antioxidant drugs. To this end, knowing the speciation of different H+-MRN and Mz+-MRN is pivotal to understand and compare their antioxidant ability. In this work, the protonation constant values of MRN under physiological ionic strength and temperature conditions (I = 0.15 mol L-1 and t = 37 °C), determined by UV-vis spectrophotometric titrations, are introduced. Thus, a reliable speciation model on H+-MRN species in aqueous solution is presented, which exhibits five stable forms depending on pH, supplemented by quantum-mechanical calculations useful to determine the proton affinities of each functional group and corresponding deprotonation order. Furthermore, potentiometry and UV-vis spectrophotometry have been exploited to determine the thermodynamic interaction parameters of MRN with different metal cations (Mg2+, Mn2+, Zn2+, Al3+). The antioxidant ability of H+-MRN and Mz+-MRN has been evaluated by the 2,2'-diphenyl-1-benzopyran-4-one (DPPH) method, and the Zn2+-MRN system has proven to afford the most potent antioxidant effect. Ab initio molecular dynamics simulations of Mz+-MRN species at all possible chelation sites and under explicit water solvation allowed for the fine characterization not only of the metal chelation modalities of MRN in explicit water, but also of the role played by the local water environment around the metal cations. Those microscopic patterns reveal to be informative on the different antioxidant capabilities recorded experimentally.

Metronidazole Interaction with Cu2+ and Zn2+: Speciation Study in Aqueous Solution and Biological Activity Evaluation.

Metronidazole (2-methyl-5-nitro-1H-imidazole-1-ethanol, MNZ) is a well-known and widely used drug for its excellent activity against various anaerobic bacteria and protozoa. The purpose of this study is to elucidate the ability of MNZ to form metal complexes with Cu2+ and Zn2+ and to demonstrate that complexation increases its bioactivity profile against different pathogenic microorganisms. The interaction of MNZ with Cu2+ and Zn2+ was investigated in NaCl aqueous solution under different conditions of temperature (15, 25, and 37 °C) and ionic strength (0.15, 0.5, and 1 mol L-1) by potentiometric and spectrophotometric titrations. The obtained speciation models include two species for the Cu2+-containing system, namely, CuL and CuL2, and three species for the Zn2+-containing system, namely, ZnLH, ZnL, and ZnLOH. The formation constants of the species were calculated and their dependence on temperature and ionic strength evaluated. Comparison of the sequestering ability of MNZ under physiological conditions revealed a capacity toward Cu2+ higher than that toward Zn2+. A simulation under the same conditions also showed a significant percentage of the Cu2+-MNZ species. The biological assessments highlighted that the complexation of MNZ with Cu2+ has a relevant impact on the potency of the drug against two Trypanosoma spp. (i.e., T. b. brucei and T. b. rhodesiense) and one gram-(-) bacterial species (i.e., Escherichia coli). It is noteworthy that the increased potency upon complexation with Cu2+ did not result in cytotoxicity against MRC-5 human fetal lung fibroblasts and primary peritoneal mouse macrophages.

Sequestering ability of some chelating agents towards methylmercury(II).

A study on the interactions between CH(3)Hg(+) and some S, N and O donor ligands (2-mercaptopropanoic acid (thiolactic acid (H(2)TLA)), 3-mercaptopropanoic acid (H(2)MPA), 2-mercaptosuccinic acid (thiomalic acid (H(3)TMA)), D,L-penicillamine (H(2)PSH), L-cysteine (H(2)CYS), glutathione (H(3)GSH), N,N'-bis(3-aminopropyl)-1-4-diaminobutane (spermine (SPER)), 1,2,3,4,5,6-benzenehexacarboxylic acid (mellitic acid (H(6)MLT)) and ethylenediaminetetraacetic acid (H(4)EDTA)) is reported. The speciation models in aqueous solution and the possible structures of the complexes formed are discussed on the basis of potentiometric, calorimetric, UV spectrophotometric and electrospray mass spectrometric results. For the CH(3)Hg(+)-S donor ligand systems, the formation of ML(1-z) and MLH(2-z) complex species is observed, together with a diprotonated MLH(2)(3-z) species for CYS(2-), PSH(2-) and GSH(3-) and the mixed hydrolytic one ML(OH)(-z) for TLA(2-) and MPA(2-). The dependence of the stability on ionic strength and on temperature is also analysed. In the other CH(3)Hg(+)-L systems (L = MLT(6-), SPER and EDTA(4-)), ML(1-z), MLH(2-z) and MLH(2)(3-z) complex species are formed, together with the MLH(3)(4-z) species for SPER, the mixed hydrolytic ML(OH)(-z) one for SPER and EDTA, and the M(2)L(2-z) for EDTA only. On the basis of the speciation models proposed, the sequestering ability of the ligands towards methylmercury(II) cation is evaluated. All S donor ligands show a good sequestering power (at 10(-11) mol L(-1) level, in the pH range 4 to 8) following the trend MPA(2-) < PSH(2-) < GSH(3-) < TLA(2-) < CYS(2-) < TMA(3-), while significantly lower is the sequestering ability of MLT, SPER and EDTA (at 10(-3)-10(-5) mol L(-1) level, in the pH range 4 to 8).

Aqueous chemistry of nalidixic acid and its complexes with biological relevant cations: A combination of potentiometric, UV spectrophotometric, MS and MS/MS study.

Nalidixic acid (NAL) is a broad-spectrum antimicrobial widely used for urinary tract infections. As demonstrated, complexation of NAL with Zn2+, Mn2+ and Cu2+ was often used to get new formulations with an enhanced efficiency and potency. Therefore, the elucidation of behavior of NAL in solution and of its interaction with metal cations are crucial to better understand the influence of complexation on NAL efficiency and to find the optimal conditions to propose novel formulations. As a preliminary study, spectrophotometric titrations were carried out on NAL to determine the values of the protonation constants and to define its acid-base behavior. Then, the interaction with the three metal cations Zn2+, Mn2+ and Cu2+ was investigated by potentiometric and spectrophotometric titrations, varying the conditions of temperature, ionic strength and metal-ligand ratio, thus allowing to get the most robust speciation model and to determine the formation constants with Zn2+, Mn2+, and Cu2+ under different conditions, the sequestering ability of NAL towards metal cations, the formation enthalpic and entropic changes. A simulation under serum conditions was reported to show the relevance of the investigated species. Finally, LD-MS (laser desorption ionization mass spectrometry) and MS/MS analyses highlighted for all systems the formation of the complex species between Zn2+, Mn2+ and Cu2+ with NAL. MS/MS investigations assigned the sites of coordination of the ligand with the metal cation. More precisely, deprotonated NAL coordinates the metal cation via the oxygens of the carboxylate and the carbonyl groups.

Thermodynamic and voltammetric study on carnosine and ferrocenyl-carnosine.

A potentiometric study on the interactions of L-carnosine (CAR) (2-[(3-aminopropanoyl)amino]-3-(1H-imidazol-5-yl)propanoic acid) with two toxic metal cations, Hg2+ and Cd2+, is reported here. The elucidation of the metal (M2+)-CAR interactions in aqueous solution highlighted the speciation model for each system, the dependence of the formation constants of the complex species on ionic strength (0.15 ≤ I/mol L-1 ≤ 1) and temperature (288.15 ≤ T/K ≤ 310.15) and changes in enthalpy and entropy. The sequestering ability of CAR towards the two metal ions was quantified and compared with that with Pb2+, previously determined. Considering the complexing ability of CAR and its unclear electrochemical properties, a more electroactive derivative, the ferrocenyl-carnosine (FcCAR), was synthesized and its complexing ability was evaluated by UV-vis spectroscopy. FcCAR electrochemical properties were investigated by Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV) on Screen-Printed Electrodes (SPEs), to evaluate its sensing properties. Electrochemical responses in the presence of Hg2+ and Pb2+ have been shown to be promising for the electrochemical detection of these metal cations in aqueous environment.

Screen-Printed Carbon Electrodes with Cationic Cyclodextrin Carbon Nanotubes and Ferrocenyl-Carnosine for Electrochemical Sensing of Hg(II).

The study reports the use of nanoassembly based on cationic cyclodextrin carbon nanotubes (CNT-CDs) and ferrocenylcarnosine (FcCAR) for electrochemical sensing of Hg(II) in aqueous solution. ß-cyclodextrins (CDs) were grafted onto CNTs by a click chemistry reaction between heptakis-(6-azido-6-deoxy)-ß-cyclodextrin and alkyne-terminated CNTs. The cationic amine groups on the CD units were produced by the subsequent reduction of the residual nitrogen groups. The chemical composition and morphology of CNT-CDs were analyzed by X-ray photoelectron spectroscopy, scanning electron microscopy, and thermogravimetric analysis. A N,N-dimethylformamide dispersion of CNT-CDs was cast on the surface of screen-printed carbon electrodes (SPCEs), and the electrochemical response was evaluated by cyclic voltammetry (CV) using [Fe(CN)6]3- as the redox probe. The ability of SPCE/CNT-CD to significantly enhance the electroactive properties of the redox probe was combined with a suitable recognition element (FcCAR) for Hg(II). The electrochemical response of the CNT-CD/FcCAR nanoassembly was evaluated by CV and electrochemical impedance spectroscopy. The analytical performance of the Hg(II) sensor was evaluated by differential pulsed voltammetry and chronoamperometry. The oxidative peak current showed a linear concentration dependence in the range of 1-100 nM, with a sensitivity of 0.12 µA/nM, a limit of detection of 0.50 nM, and a limit of quantification of 1 nM.

Coronary in-stent restenosis: assessment with CT coronary angiography.

PURPOSE: To compare accuracy and radiation exposure of a new computed tomographic (CT) scanner with improved spatial resolution (scanner A) with those of a CT scanner with standard spatial resolution (scanner B) for evaluation of coronary in-stent restenosis (ISR) by using invasive coronary angiography (ICA) and intravascular ultrasonography (US) as reference methods. MATERIALS AND METHODS: Written informed consent was obtained and study protocol was approved by institutional ethics committee. A total of 180 consecutive patients (154 men [mean age ± standard deviation, 66 years±12; range, 51-79 years] and 36 women [mean age, 70 years±12; range, 55-83 years]) scheduled to undergo ICA for suspected ISR were enrolled. Ninety patients were studied with scanner A (group 1: 72 men [mean age, 65 years±11; range, 52-79], 18 women [mean age, 68 years±12; range, 55-83 years]) and 90 with scanner B (group 2: 74 men [mean age, 64 years±10; range, 51-77 years], 16 women [mean age, 68 years±11; range, 55-82 years). Examination with the two scanners was compared with ICA and intravascular US. Radiation dose exposure was estimated. To compare stent evaluability between the two groups, χ2 test was used. RESULTS: Stent evaluability was higher in group 1 than in group 2 (99% vs 92%, P=.0021). A significantly lower rate of beam-hardening artifact was observed in group 1 (two cases) than group 2 (12 cases, P<.05). For stent-based analysis, sensitivity, specificity, and accuracy of multidetector CT for ISR identification were 96%, 95%, and 96% in group 1 and 90%, 91%, and 91% in group 2, respectively, without statistically significant differences. The correlation between percent ISR evaluated at multidetector CT versus intravascular US was higher in group 1 than in group 2 (r=0.89 vs r=0.58; P=.019). The correlations of diameter and area measurements at reference site and stent maximal lumen narrowing site between multidetector CT and intravascular US were higher in group 1 than in group 2. Radiation dose was low in both multidetector CT groups (1.9 mSv±0.2). CONCLUSION: Scanner A, with improved spatial resolution, allowed reliable detection and quantification of coronary ISR with low radiation exposure.

Aortic annulus area assessment by multidetector computed tomography for predicting paravalvular regurgitation in patients undergoing balloon-expandable transcatheter aortic valve implantation: a comparison with transthoracic and transesophageal echocardiography.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a valid alternative to surgery in high-risk patients with severe aortic stenosis. Aortic annulus (AoA) sizing is crucial for TAVI success. The aim of the study was to compare AoA dimensions measured by multidetector computed tomography (MDCT) vs those obtained with transthoracic (TTE) and transesophageal echocardiography (TEE) for predicting paravalvular aortic regurgitation (PVR) after TAVI. METHODS: Aortic annulus maximum diameter, minimum diameter, and area were assessed using MDCT and compared with TTE and TEE diameter and area for predicting PVR after TAVI in 151 patients (45 men, age 81.2 ± 6.4 years). RESULTS: Aortic annulus maximum, minimum diameter, and area detected by MDCT were 25.04 ± 2.39 mm, 21.27 ± 2.10 mm, and 420.87 ± 76.10 mm(2), respectively. Aortic annulus diameter and area measured by TTE and TEE were 21.14 ± 1.94 mm and 353.82 ± 64.57 mm(2) and 22.04 ± 1.94 mm and 384.33 ± 67.30 mm(2), respectively. A good correlation was found between AoA diameters and area evaluated by MDCT vs TTE and TEE (0.61, 0.65, and 0.69 and 0.61, 0.65, and 0.70, respectively), with a mean difference of 3.90 ± 1.98 mm, 0.13 ± 1.67 mm, and 67.05 ± 55.87 mm(2) and 3.0 ± 2.0 mm, 0.77 ± 1.70 mm, and 36.54 ± 56.43 mm(2), respectively. Grade ≥2 PVR occurred in 46 patients and was related to male gender, higher body mass index, preprocedural aortic regurgitation, and lower mismatch between the nominal area of the implanted prosthesis and AoA area detected by MDCT. CONCLUSIONS: Mismatch between prosthesis area and AoA area detected by MDCT is a better predictor of PVR as compared with echocardiography mismatch. Specific MDCT-based sizing recommendations should be developed.

Metal-Based Compounds in Antiviral Therapy.

In recent years, the study of metal complexes and metal-based nanomaterials has aroused particular interest, leading to the promotion of new effective systems for the abatement of various viral diseases. Starting from the analysis of chemical properties, this review focuses on the employment of metal-based nanoparticles as antiviral drugs and how this interaction leads to a substantial enhancement in antiviral activity. The use of metal-based antiviral drugs has also spread for the formulation of antiviral vaccines, thanks especially to the remarkable adjuvant activities of some of the metal complexes. In particular, the small size and inert nature of Au- and Ag-based nanoparticles have been exploited for the design of systems for antiviral drug delivery, leading to the development of specific and safe therapies that lead to a decrease in side effects.

Speciation Study on O-Phosphorylethanolamine and O-Phosphorylcholine: Acid-Base Behavior and Mg2+ Interaction.

In the present study, the acid-base behavior of compounds constituting the headgroups of biomembranes, O-phosphorylethanolamine (PEA), and O-phosphorylcholine (PPC) was investigated by potentiometric titrations in NaCl aqueous solutions at different temperatures (15 ≤ t/°C ≤ 37) and ionic strength (0.15 ≤ I/mol L-1 ≤ 1) values. The complexation properties and the speciation of these ligands with Mg2+ were defined under different temperatures (15 ≤ t/°C ≤ 37) and I = 0.15 mol L-1. The results evidenced the formation of three species for PEA, namely, MLH2, MLH, and ML and two species for PPC, namely, MLH and ML. 1H-NMR titrations were performed on solutions containing ligand and metal-ligand solutions at t = 25°C and I = 0.15 mol L-1. The estimated values of ligand protonation and complex formation constants and the speciation model are in accordance with the potentiometric data. The enthalpy changes were also determined at t = 25°C and I = 0.15 mol L-1 by the dependence of formation constants on the temperature, confirming the electrostatic nature of the interactions. Matrix-assisted laser desorption mass spectrometry (MALDI-MS) was applied for the characterization of Mg2+-L systems (L = PEA or PCC). MS/MS spectra of free ligands and of Mg2+-L species were obtained. The observed fragmentation patterns of both Mg2+-L systems allowed elucidating the interaction mechanism that occurs via the phosphate group generating a four-membered cycle.

Ca2+ Complexation With Relevant Bioligands in Aqueous Solution: A Speciation Study With Implications for Biological Fluids.

A speciation study on the interaction between Ca2+ and ligands of biological interest in aqueous solution is reported. The ligands under study are l-cysteine (Cys), d-penicillamine (PSH), reduced glutathione (GSH), and oxidized glutathione (GSSG). From the elaboration of the potentiometric experimental data the most likely speciation patterns obtained are characterized by only protonated species with a 1:1 metal to ligand ratio. In detail, two species, CaLH2 and CaLH, for systems containing Cys, PSH, and GSH, and five species, CaLH5, CaLH4, CaLH3, CaLH2, and CaLH, for system containing GSSG, were observed. The potentiometric titrations were performed at different temperatures (15 ≤ t/°C ≤ 37, at I = 0.15 mol L-1). The enthalpy and entropy change values were calculated for all systems, and the dependence of the formation constants of the complex species on the temperature was evaluated. 1H NMR spectroscopy, MALDI mass spectrometry, and tandem mass spectrometry (MS/MS) investigations on Ca2+-ligand solutions were also employed, confirming the interactions and underlining characteristic complexing behaviors of Cys, PSH, GSH, and GSSG toward Ca2+. The results of the analysis of 1H NMR experimental data are in full agreement with potentiometric ones in terms of speciation models and stability constants of the species. MALDI mass spectrometry and tandem mass spectrometry (MS/MS) analyses confirm the formation of Ca2+-L complex species and elucidate the mechanism of interaction. On the basis of speciation models, simulations of species formation under conditions of some biological fluids were reported. The sequestering ability of Cys, PSH, GSH, and GSSG toward Ca2+ was evaluated under different conditions of pH and temperature and under physiological condition.