A New Chemometrically Assisted UV Spectrophotometric Method for Simultaneous Determination of Tamsulosin and Dutasteride in Their Pharmaceutical Mixture.

BACKGROUND: Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT in terms of their ability to protect against recent COVID-19. However, very few studies were reported for their simultaneous quantification in their combined dosage form and were mainly based on chromatographic analysis. Subsequently, it is very important to offer a simple, selective, sensitive, and rapid method for the quantification of TAM and DUT in their challenging dosage form. OBJECTIVE: In this study, a new chemometrically assisted ultraviolet (UV) spectrophotometric method has been presented for the quantification of TAM and DUT without any prior separation. METHOD: For the calibration set, a partial factorial experimental design was used, resulting in 25 mixtures with central levels of 20 and 25 µg/mL for TAM and DUT, respectively. In addition, to assess the predictive ability of the developed approaches, another central composite design of 13 samples was used as a validation set. Post-processing by chemometric analysis of the recorded zero-order UV spectra of these sets has been applied. These chemometric approaches include partial least-squares (PLS) and genetic algorithm (GA), as an effective variable selection technique, coupled with PLS. RESULTS: The models' validation criteria displayed excellent recoveries and lower errors of prediction. CONCLUSIONS: The proposed models were effectively used to determine TAM/DUT in their combined dosage form, and statistical comparison with the reported method revealed satisfactory results. HIGHLIGHTS: Overall, this work presents powerful simple, selective, sensitive, and precise methods for simultaneous quantification of TAM/DUT in their dosage form with satisfactory results. The predictive ability and accuracy of the developed methods offer the opportunity to be employed as a quality control technique for the routine analysis of TAM/DUT when chromatographic instruments are not available.

Two Green Micellar HPLC and Mathematically Assisted UV Spectroscopic Methods for the Simultaneous Determination of Molnupiravir and Favipiravir as a Novel Combined COVID-19 Antiviral Regimen.

Following the spread of the COVID-19 pandemic crisis, a race was initiated to find a successful regimen for postinfections. Among those trials, a recent study declared the efficacy of an antiviral combination of favipiravir (FAV) and molnupiravir (MLP). The combined regimen helped in a successful 60% eradication of the SARS-CoV-2 virus from the lungs of studied hamster models. Moreover, it prevented viral transmission to cohosted sentinels. Because both medications are orally bioavailable, the coformulation of FAV and MLP can be predicted. The developed study is aimed at developing new green and simple methods for the simultaneous determination of FAV and MLP and then at their application in the study of their dissolution behavior if coformulated together. A green micellar HPLC method was validated using an RP-C18 core-shell column (5 µm, 150 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.1 M SDS, 0.01 M Brij-35, and 0.02 M monobasic potassium phosphate mixture and adjusted to pH 3.1 at 1.0 mL min-1 flow rate. The analytes were detected at 230 nm. The run time was less than five minutes under the optimized chromatographic conditions. Four other multivariate chemometric model methods were developed and validated, namely, classical least square (CLS), principal component regression (PCR), partial least squares (PLS-1), and genetic algorithm-partial least squares (GA-PLS-1). The developed models succeeded in resolving the great similarity and overlapping in the FAV and MLP UV spectra unlike the traditional univariate methods. All methods were organic solvent-free, did not require extraction or derivatization steps, and were applied for the construction of the simultaneous dissolution profile for FAV tablets and MLP capsules. The methods revealed that the amount of the simultaneously released cited drugs increases up until reaching a plateau after 15 and 20 min for FAV and MLP, respectively. The greenness was assessed on GAPI and found to be in harmony with green analytical chemistry concepts.

Metal oxide nanocage as drug delivery systems for Favipiravir, as an effective drug for the treatment of COVID-19: a computational study.

This paper is a summary of research that looks at the potential of fullerene-like (MO)12 nanoclusters (NCs) in drug-carrying systems using density functional theory. Favipiravir/Zn12O12 (- 34.80 kcal/mol), Favipiravir/Mg12O12 (- 34.98 kcal/mol), and Favipiravir/Be12O12 (- 30.22 kcal/mol) were rated in order of drug adsorption degrees. As a result, Favipiravir attachment to (MgO)12 and (ZnO)12 might be simple, increasing Favipiravir loading efficiency. In addition, the quantum theory of atoms in molecules (QTAIM) assessment was utilized to look at the interactions between molecules. The FMO, ESP, NBO, and Eads reactivity patterns were shown to be in excellent agreement with the QTAIM data. The electrostatic properties of the system with the biggest positive charge on the M atom and the largest Eads were shown to be the best. This system was shown to be the best attraction site for nucleophilic agents. The findings show that (MgO)12 and (ZnO)12 have great carrier potential and may be used in medication delivery.

On the Weak Binding and Spectroscopic Signature of SARS-CoV-2 nsp14 Interaction with RNA.

The SARS-CoV-2 non-structural protein 14 (nsp14), known as exoribonuclease is encoded from the large polyprotein of viral genome and is a major constituent of the transcription replication complex (TRC) machinery of the viral RNA synthesis. This protein is highly conserved among the coronaviruses and is a potential target for the development of a therapeutic drug. Here, we report the SARS-CoV-2 nsp14 expression, show its structural characterization, and ss-RNA exonuclease activity through vibrational and electronic spectroscopies. The deconvolution of amide-I band in the FTIR spectrum of the protein revealed a composition of 35 % α-helix and 25 % ß-sheets. The binding between protein and RNA is evidenced from the spectral changes in the amide-I region of the nsp14, showing protein conformational changes during the binding process. A value of 20.60±3.81 mol L-1 of the binding constant (KD ) is obtained for nsp14/RNA complex. The findings reported here can motivate further studies to develop structural models for better understanding the mechanism of exonuclease enzymes for correcting the viral genome and can help in the development of drugs against SARS-CoV-2.

Human tear fluid analysis for clinical applications: progress and prospects.

Introduction: Human blood and saliva are increasingly under investigation for the detection of biomarkers for early diagnosis of non-communicable (e.g.cancers) and communicable diseases like COVID-19. Exploring the potential application of human tears, an easily accessible body fluid, for the diagnosis of various diseases is the need of the hour.Areas covered: This review deals with a comprehensive account of applications of tear analysis using different techniques, their comparison and overall progress achieved till now. The techniques used for tear fluid analysis are HPLC/UPLC/SDS-PAGE, CE, etc., together with ELISA, Mass Spectrometry, etc. But, with advances in instrumentation and data processing methods, it has become easy to couple the various separation methods with highly sensitive optical techniques for the analysis of body fluids.Expert opinion: Tear analysis can provide valuable information about the health condition of the eyes since it contains several molecular constituents, and their relative concentrations may alter under abnormal conditions. Tear analysis has the advantage that it is totally non-invasive. This study recommends tear fluid as a reliable clinical sample to be probed by highly sensitive optical techniques to diagnose different health conditions, with special emphasis on eye diseases.

Tuning the Computational Evaluation of Spectroscopic, ELF, LOL, NCI analysis and Molecular Docking of Novel Anti COVID-19 Molecule 4-Dimethylamino Pyridinium 3, 5-Dichlorosalicylate.

In this work novel antiviral compound 4-(Dimethylamino) Pyridinium 3, 5-dichlorosalicylate was synthesized and characterized by UV-vis, FT-IR, FT-Raman, 1H NMR and 13C NMR spectra. Quantum chemical computations were carried out by Density functional theory methods at B3LYP level. Electronic stability of the compound arising from hyper conjugative interactions and charge delocalization is investigated using natural bond orbital analysis. Assignments of vibrational spectra have been carried out with the aid of Normal coordinate analysis following the SQMFF methodology. TD-DFT approach was applied to assign the electronic transition observed in UV visible spectrum measured experimentally. Frontier molecular orbital energy gap affirms the bioactivity of the molecule and NCI analysis gives information about inter and intra non covalent interactions. ESP recognises the nucleophilic and electrophilic regions of molecule and the chemical implication of molecule was explained using ELF, LOL. The reactive sites of the compound were studied from the Fukui function calculations and chemical descriptors define the reactivity of the molecule. Molecular docking done with SARS and MERS proteins endorses the bioactivity of molecule and drug likeness factors were calculated to comprehend the biological assets of DADS.

Assessment of saliva interference with UV-based disinfection technologies.

Worldwide shortages of personal protective equipment during COVID-19 pandemic has forced the implementation of methods for decontaminating face piece respirators such as N95 respirators. The use of UV irradiation to reduce bioburden of used respirators attracts attention, making proper testing protocols of uttermost importance. Currently artificial saliva is used but its comparison to human saliva from the UV disinfection perspective is lacking. Here we characterize UV spectra of human and artificial saliva, both fresh and after settling, to test for possible interference for UV-based disinfection. ASTM 2720 artificial saliva recipe (with either porcine or bovine mucin) showed many discrepancies from average (N = 18) human saliva, with different mucins demonstrating very different UV absorbance spectra, resulting in very different UV transmittance at different wavelength. Reducing porcine mucin concentration from 3 to 1.7 g/L brought UVA254 in the artificial saliva to that of average human saliva (although not for other wavelengths), allowing 254 nm disinfection experiments. Phosphate saline and modified artificial saliva were spiked with 8.6 log CFU/ml B. subtilis spores (ATCC 6633) and irradiated at dose of up to 100 mJ/cm2, resulting in 5.9 log inactivation for a saline suspension, and 2.8 and 1.1 log inactivation for ASTM-no mucin and ASTM-1.7 g/L porcine mucin 2 µL dried droplets, respectively. UVC irradiation of spores dried in human saliva resulted in 2.3 and 1.5 log inactivation, depending on the size of the droplets (2 vs 10 µL, respectively) dried on a glass surface. Our results suggest that in the presence of the current standard dried artificial saliva it is unlikely that UVC can achieve 6 log inactivation of B. subtilis spores using a realistic UV dose (e.g. less than 2 J/cm2) and the ATSM saliva recipe should be revised for UV decontamination studies.

Synthesis, structural, spectral, antioxidant, bioactivity and molecular docking investigations of a novel triazole derivative.

The structural, spectroscopic and electronic properties of 4-(4-nitrophenyl)-5-(pyridin-3-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione have been analyzed by using single crystal X-ray diffraction (SCXRD), 1H and 13C NMR chemical shifts and FT-IR spectroscopic methods both theoretically and experimentally. The tautomeric (thiol and thione) energetic analysis results, structural optimization parameters (bond lengths and angles), vibrational wavenumbers, proton and carbon NMR chemical shifts, UV-Vis. parameters, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) analyses and Molecular Electrostatic Potential (MEP) surface have been calculated by using DFT/B3LYP quantum chemical method with 6-311++G(2d,2p) basis set to compare with the experimental results. The computed geometry parameters, vibrational wavenumbers, and NMR chemical shifts have been in good agreement with the experimental results. It should be noted that the radical scavenging activities of the title compound have been evaluated by using different test methods i.e. 2,2-Diphenyl-1-picrylhydrazyl (DPPH), N,N-dimethyl-p-phenylenediamine (DMPD) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS). According to obtained results, the title compound displayed DPPH (SC50 19.42 ± 0.11 µg/mL), DMPD (SC50 21.13 ± 0.08 µg/mL) and ABTS (SC50 38.17 ± 0.25 µg/mL) scavenging activities. Also, these results have been compared with Butylated hydroxyanisole (BHA), Rutin (RUT) and Trolox (TRO) used as standard compounds. The physicochemical, pharmacokinetic, and toxicity features of the compound have been determined by using drug-likeness and in silico ADMET investigations. The interaction results with SARS-CoV-2 main protease (Mpro) of the title ligand compound have been analyzed via the help of molecular docking study. Communicated by Ramaswamy H. Sarma.

Rapid Detection of SARS-CoV-2 Antigens Using High-Purity Semiconducting Single-Walled Carbon Nanotube-Based Field-Effect Transistors.

Early diagnosis of SARS-CoV-2 infection is critical for facilitating proper containment procedures, and a rapid, sensitive antigen assay is a critical step in curbing the pandemic. In this work, we report the use of a high-purity semiconducting (sc) single-walled carbon nanotube (SWCNT)-based field-effect transistor (FET) decorated with specific binding chemistry to assess the presence of SARS-CoV-2 antigens in clinical nasopharyngeal samples. Our SWCNT FET sensors, with functionalization of the anti-SARS-CoV-2 spike protein antibody (SAb) and anti-nucleocapsid protein antibody, detected the S antigen (SAg) and N antigen (NAg), reaching a limit of detection of 0.55 fg/mL for SAg and 0.016 fg/mL for NAg in calibration samples. SAb-functionalized FET sensors also exhibited good sensing performance in discriminating positive and negative clinical samples, indicating a proof of principle for use as a rapid COVID-19 antigen diagnostic tool with high analytical sensitivity and specificity at low cost.

Antimicrobial properties of diethylamine NONOate, a nitric oxide donor, against Escherichia coli: a pilot study.

The emergence of SARS-CoV-2, the causative agent of COVID-19, highlights the increasing need for new and effective antiviral and antimicrobial agents. The FDA has recently banned several active ingredients used in hand sanitizers, including triclosan and benzethonium chloride. Nitric oxide (NO) is involved in the innate immune response and is a major component of macrophage-mediated attack on foreign viruses and bacteria. The specific aim of this study was to assess the antibacterial effects of 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NONOate) against Escherichia coli (E. coli). A bacterial growth assay was compared to an adenosine triphosphate (ATP) activity assay at various time points to assess effects of DEA-NONOate on E. coli growth. A UV/Vis spectrophotometer was used to determine concentration of E. coli by measuring optical density (OD) at 630 nm. A luminescent assay was used to measure ATP activity correlating to viable cells. DEA-NONOate at a concentration of 65 mM was able to inhibit the growth of E. coli with the same efficacy as 1 µg ml-1 concentration of ciprofloxacin. Both the OD and ATP assays demonstrated a 99.9% reduction in E. coli. Both a 1 µg ml-1 concentration of ciprofloxacin and a 65 mM concentration of DEA-NONOate achieved 99.9% inhibition of E. coli, verified using both optical density measurement of bacterial cultures in 96 well plates and a luminescent ATP activity assay. The bactericidal effects of DEA-NONOate against E. coli is proof-of-concept to pursue evaluation of nitric oxide-based formulations as antimicrobial and antiviral agents as hand sanitizers.

A new approach for the determination of sunscreen levels in seawater by ultraviolet absorption spectrophotometry.

Sunscreen is released into the marine environment and is considered toxic for marine life. The current analytical methods for the quantification of sunscreen are mostly specific to individual chemical ingredients and based on complex analytical and instrumental techniques. A simple, selective, rapid, reproducible and low-cost spectrophotometric procedure for the quantification of commercial sunscreen in seawater is described here. The method is based on the inherent properties of these cosmetics to absorb in the wavelength of 300-400 nm. The absorption at 303 nm wavelength correlates with the concentration of most commercial sunscreens. This method allows the determination of sunscreens in the range of 2.5-1500 mg L-1, it requires no sample pretreatment and offers a precision of up to 0.2%. The spectrophotometric method was applied to quantify sunscreen concentrations at an Atlantic Beach with values ranging from 10 to 96.7 mg L-1 in the unfiltered fraction and from the undetectable value to 75.7 mg L-1 in the dissolved fraction. This method is suggested as a tool for sunscreen quantifications in environmental investigations and monitoring programs.

Simulating Absorption Spectra of Flavonoids in Aqueous Solution: A Polarizable QM/MM Study.

We present a detailed computational study of the UV/Vis spectra of four relevant flavonoids in aqueous solution, namely luteolin, kaempferol, quercetin, and myricetin. The absorption spectra are simulated by exploiting a fully polarizable quantum mechanical (QM)/molecular mechanics (MM) model, based on the fluctuating charge (FQ) force field. Such a model is coupled with configurational sampling obtained by performing classical molecular dynamics (MD) simulations. The calculated QM/FQ spectra are compared with the experiments. We show that an accurate reproduction of the UV/Vis spectra of the selected flavonoids can be obtained by appropriately taking into account the role of configurational sampling, polarization, and hydrogen bonding interactions.

3,3',5,5'-tetramethylbenzidine as multi-colorimetric indicator of chlorine in water in line with health guideline values.

Sanitizing solutions against bacterial and viral pathogens are of utmost importance in general and, in particular, in these times of pandemic due to Sars-Cov2. They frequently consist of chlorine-based solutions, or in the direct input of a certain amount of chlorine in water supply systems and swimming pools. Colorimetry is one of the techniques used to measure the crucial persistence of chlorine in water, including household chlorine test kits commonly based on colorimetric indicators. Here, we show a simple and cheap colorimetric method based on 3,3',5,5'-tetramethylbenzidine (TMB), commonly used as chromogenic reagent for enzyme-linked immunosorbent assays. TMB is converted by chlorine to a colored molecule through a pH-dependent multi-step oxidation process where the chromaticity of TMB is directly proportional to chlorine content. This molecule offers several advantages over other commonly used reagents in terms of safety, sensitivity, and, peculiarly, hue modulation, giving rise to the detection of chlorine in water with a multi-color change of the indicator solution (transparent/blue/green/yellow). Moreover, through the appropriate setting of reaction conditions, such coloration is finely tunable to cover the range of chlorine concentration recommended by international health agencies for treatment of drinking water and swimming pools and to test homemade solutions prepared by dilution of household bleach during health emergency events such as during the current pandemic. Graphical abstract.