Charge Transfer Complex of Lorlatinib with Chloranilic Acid: Characterization and Application to the Development of a Novel 96-Microwell Spectrophotometric Assay with High Throughput.

Lorlatinib (LRL) is the first drug of the third generation of anaplastic lymphoma kinase (ALK) inhibitors used a first-line treatment of non-small cell lung cancer (NSCLC). This study describes, for the first time, the investigations for the formation of a charge transfer complex (CTC) between LRL, as electron donor, with chloranilic acid (CLA), as a π-electron acceptor. The CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational calculations. The UV-visible spectrophotometry ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 0.55 × 103 L mol-1 cm-1 and its band gap energy was 2.3465 eV. The stoichiometric ratio of LRL/CLA was found to be 1:2. The association constant of the complex was 0.40 × 103 L mol-1, and its standard free energy was -0.15 × 102 J mole-1. The computational calculation for the atomic charges of an energy minimized LRL molecule was conducted, the sites of interaction on the LRL molecule were assigned, and the mechanism of the reaction was postulated. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for LRL. The assay limits of detection and quantitation were 2.1 and 6.5 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of LRL in its bulk form and pharmaceutical formulation (tablets). This assay is simple, economic, and more importantly has a high-throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of LRL's bulk form and pharmaceutical tablets.

One-Step Microwell Plate-Based Spectrofluorimetric Assay for Direct Determination of Statins in Bulk Forms and Pharmaceutical Formulations: A Green Eco-Friendly and High-Throughput Analytical Approach.

This study describes the development of a one-step microwell spectrofluorimetric assay (MW-SFA) with high sensitivity and throughput for the determination of four statins in their pharmaceutical and formulations (tablets). These statins were pitavastatin (PIT), fluvastatin (FLU), rosuvastatin (ROS) and atorvastatin (ATO). The MW-SFA involves the measurement of the native fluorescence of the statin aqueous solutions. The assay was conducted in white opaque 96-microwell plates, and the fluorescence intensities of the solutions were measured by using a fluorescence microplate reader. The optimum conditions of the assay were established; under which, linear relationships with good correlation coefficients (0.9991-0.9996) were found between the fluorescence intensity and the concentration of the statin drug in a range of 0.2-200 µg mL-1 with limits of detection in a range of 0.1-4.1 µg mL-1. The proposed MW-SFA showed high precision, as the values of the relative standard deviations did not exceed 2.5%. The accuracy of the assay was proven by recovery studies, as the recovery values were 99.5-101.4% (±1.4-2.1%). The assay was applied to the determination of the investigated statins in their tablets. The results were statistically compared with those obtained by a reference method and the results proved to have comparable accuracy and precision of both methods, as evidenced by the t- and F-tests, respectively. The green and eco-friendly feature of the proposed assay was assessed by four different metric tools, and all the results proved that the assay meets the requirements of green and eco-friendly analytical approaches. In addition, ever-increasing miniaturization as handling of large numbers of micro-volume samples simultaneously in the proposed assay gave it a high-throughput feature. Therefore, the assay is a valuable tool for the rapid routine application in the pharmaceutical quality control units for the determination of statins.

Selective Stability Indicating Liquid Chromatographic Method Based on Quality by Design Framework and In Silico Toxicity Assessment for Infigratinib and Its Degradation Products.

Infigratinib, a protein kinase inhibitor employed in the therapeutic management of cholangiocarcinoma, was subjected to various stress conditions, including hydrolytic (acidic and alkaline), oxidative, photolytic, and thermal stress, in accordance with the rules established by the International Council for Harmonization. A cumulative count of five degradation products was observed. The application of the Quality by Design principle was utilized in the development of a rapid and specific separation method for Infigratinib and its degradation products. The methodology employed in this study was derived from an experimental design approach, which was utilized to examine the critical process parameters associated with chromatographic systems. The reversed-phase high-performance liquid chromatography technique, employing a C18 column and a mobile phase composed of a gradient mixture of 25 mM ammonium acetate buffer at pH 6.0 and acetonitrile, successfully facilitated the chromatographic separation. The methodology was expanded to include the utilization of UPLC-quadrupole tandem mass spectrometry in order to conduct a comprehensive analysis of the structural properties and characterize the degradation products. Overall, five degradation products were found in different stress conditions. The method was verified at certain working points, wherein a linearity range (5.0-200.0 µg/mL) was developed and other parameters such as accuracy, repeatability, selectivity, and system suitability were evaluated. Finally, the toxicity and mutagenicity of Infigratinib and its degradation products were predicted using in silico software, namely DEREK Nexus® (version 6.2.1) and SARAH Nexus® (version 3.2.1). Various toxicity endpoints, including chromosomal damage, were predicted. Additionally, two degradation products were also predicted to be mutagenic.

Comparative Study of Augmented Classical Least Squares Models for UV Assay of Co-Formulated Antiemetics Together with Related Impurities.

The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and meclizine HCl (MEC) in a quinary mixture with two related impurities: the CYC main impurity, Benzhydrol (BEH), which has carcinogenic and hepatotoxic effects, and the MEC official impurity, 4-Chlorobenzophenone (BEP). The proposed augmented CLS models are orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS), and net analyte processing CLS (NAP-CLS). These models were applied to quantify the three active constituents in their raw materials and their corresponding dosage forms using their UV spectra. To evaluate the CLS-based models sensibly, we design a comparative study involving two sets: the training set to construct models and the validation set to assess the prediction abilities of these models. A five-level, five-factor calibration design was established to produce 25 mixtures for the calibration set. In addition, 16 experiments were performed for a test set distributed equally between the in-space and out-space samples. The primary criterion for comparing the models' performance was the validation set's root mean square error of prediction (RMSEP) value. Finally, augmented CLS models showed acceptable results for assaying the three analytes. The results were compared statistically with the reported HPLC methods; however, the DOSC-CLS model proved the best for assaying the dosage forms.

Antioxidant and Anti-Aging Phytoconstituents from Faucaria tuberculosa: In Vitro and In Silico Studies.

Research targeting natural cosmeceuticals is now increasing due to the safety and/or limited side effects of natural products that are highly valued in cosmetology. Within a research program exploring botanical sources for valuable skincare antioxidant components, the current study investigated the phytochemical content and the biological potential of Faucaria tuberculosa. Phytochemical investigation of F. tuberculosa extract resulted in purification and characterization of six phytoconstituents, including a new one. The structure of the new constituent was elucidated as (-) catechin-(2→1',4→2')-phloroglucinol (4). The structural identity of all isolated compounds were confirmed on the basis of extensive physical and spectral (1D, 2D-NMR and HRESIMS) investigations. The ethanolic extract exhibits a rich content of total phenolics (TPC) and total flavonoids (TFC), estimated as 32 ± 0.034 mg GAE/g and 43 ± 0.004 mg RE/g, respectively. In addition, the antioxidant (ABTS and FRAP), antihyaluronidase and antityrosinase activities of all purified phytoconstituents were evaluated. The results noted (-) catechin-(2→1',4→2') phloroglucinol (4) and phloroglucinol (1) for their remarkable antioxidant activity, while isorhamnetin 3-O-rutinoside (3) and 3,5-dihydroxyphenyl ß-D-glucopyranoside (2) achieved the most potent inhibitory activity against tyrosinase (IC50 22.09 ± 0.7 µM and 29.96 ± 0.44 µM, respectively) and hyaluronidase enzymes (IC50 49.30 ± 1.57 µM and 62.58 ± 0.92, respectively) that remarkably exceeds the activity of the standard drugs kojic acid (IC50 = 65.21 ± 0.47 µM) and luteolin, (IC50 = 116.16 ± 1.69 µM), respectively. A molecular docking study of the two active compounds (3 and 2) highlighted their high potential to bind to the active sites of the two enzymes involved in the study.

Novel High-Throughput Microwell Spectrophotometric Assay for One-Step Determination of Lorlatinib, a Novel Potent Drug for the Treatment of Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer.

Background and Objectives: Lorlatinib (LOR) belongs to the third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. People who are diagnosed with ALK-positive metastatic and advanced non-small cell lung cancer (NSCLC) are eligible to get it as a first-line treatment option after it was given the approval by "the Food and Drug Administration (FDA)". However, no study has described constructing high-throughput analytical methodology for LOR quantitation in dosage form. For the first time, this work details the construction of a high-throughput, innovative microwell spectrophotometric assay (MW-SPA) for single-step assessment of LOR in its tablet form, for use in pharmaceutical quality control. Materials and Methods: Assay depended on charge transfer complex (CTC) formation between LOR, as electron donor, with 2,3-dichloro-3,5-dicyano-1,4-benzoquinone (DDQ), as π-electron acceptor. Reaction conditions were adjusted, the CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational molecular modeling, and its electronic constants were determined. Site of interaction on LOR molecule was allocated and reaction mechanism was suggested. Under refined optimum reaction conditions, the procedures of MW-SPA were performed in 96-well assay plates, and the responses were recorded by an absorbance plate reader. Validation of the current methodology was performed in accordance with guidelines of "the International Council on Harmonization (ICH)", and all validation parameters were acceptable. Results: Limits of detection and quantitation of MW-SPA were 1.8 and 5.5 µg/well, respectively. The assay was applied with great success for determining LOR in its tablets. Conclusions: This The assay is straightforward, economic and has high-throughput characteristics. Consequently, the assay is recommended as a valuable analytical approach in quality control laboratories for LOR's tablets' analysis.

Spectrophotometric Investigations of Charge Transfer Complexes of Tyrosine Kinase Inhibitors with Iodine as a σ-Electron Acceptor: Application to Development of Universal High-Throughput Microwell Assay for Their Determination in Pharmaceutical Formulations.

Background and Objective: Tyrosine kinase inhibitors (TKIs) are used for the treatment of different types of cancers. The current study describes, for the first time, the ultraviolet-visible spectrophotometric investigation of charge transfer complexes (CTCs) of seven TKIs, as electron donors, and iodine, as σ-electron. Materials and Methods: The formation of CTCs was promoted in dichloromethane, among the other solvents used in the investigation. The molar absorptivity values, association constants, and free energy changes of the CTCs were determined. Stoichiometric ratio of TKI: iodine as well as TKIs site(s) of interaction were addressed. Reaction was the basis for constructing a novel simple and accurate 96-microwell spectrophotometric assay (MW-SPA) with high-throughput property for the quantitative determination of TKIs in their pharmaceutical formulations. Results: Beer's law, which relates CTC absorbances to TKI concentrations, was followed within the optimal range of 2 to 100 µg/well (r ranged from 0.9991 to 0.9998). Detection and quantification limits ranged from 0.91 to 3.60 and 2.76 to 10.92 g µmL-1, respectively. Relative standard deviations values for the intra- and inter-assay precisions of the proposed MW-SPA did not exceed 2.13 and 2.34%, respectively. Studies of recovery demonstrated MW-SPA accuracy, with results ranging from 98.9% to 102.4%. All TKIs, both in bulk form and in pharmaceutical formulations (tablets), were effectively determined using the suggested MW-SPA. Conclusions: The current MW-SPA involved a simple procedure and it was convenient as it could analyse all proposed TKIs utilizing a single assay system at once measuring wavelengths for all TKIs. In addition, the proposed MW-SPA has high throughput which enables the processing of a batch of huge samples' number in very short reasonable time period. In conclusion, TKIs can be routinely analysed in their dosage forms in quality control laboratories, and the assay can be highly valuable and helpful in this regard.

Development of Novel Microwell-Based Spectrofluorimetry and High-Performance Liquid Chromatography with Fluorescence Detection Methods and High Throughput for Quantitation of Alectinib in Bulk Powder and Urine Samples.

Background and Objectives: This study presents the development and validation of the 96-microwell-based spectrofluorimetric (MW-SFL) and high performance liquid chromatography (HPLC) with fluorescence detection (HPLC-FD) methods for the quantitation of alectinib (ALC) in its bulk powder form and in urine samples. Materials and Methods: The MW-SFL was based on the enhancement of the native fluorescence of ALC by the formation of micelles with the surfactant cremophor RH 40 (Cr RH 40) in aqueous media. The MW-SFL was executed in a 96-microwell plate and the relative fluorescence intensity (RFI) was recorded by utilizing a fluorescence plate reader at 450 nm after excitation at 280 nm. The HPLC-FD involved the chromatographic separation of ALC and ponatinib (PTB), as an internal standard (IS), on a C18 column and a mobile phase composed of methanol:potassium dihydrogen phosphate pH 7 (80:20, v/v) at a flow rate of 2 mL min-1. The eluted ALC and PTB were detected by utilizing a fluorescence detector set at 365 nm for excitation and 450 nm for emission. Results: Validation of the MW-SFL and HPLC-FD analytical methods was carried out in accordance with the recommendations issued by the International Council for Harmonization (ICH) for the process of validating analytical procedures. Both methods were efficaciously applied for ALC quantitation in its bulk form as well as in spiked urine; the mean recovery values were ≥86.90 and 95.45% for the MW-SFL and HPLC-FD methods, respectively. Conclusions: Both methodologies are valuable for routine use in quality control (QC) laboratories for determination of ALC in pure powder form and in human urine samples.

Synthesis, spectroscopic and computational characterization of charge transfer complex of remdesivir with chloranilic acid: Application to development of novel 96-microwell spectrophotometric assay.

Remdesivir (REM) is an adenosine triphosphate analog antiviral drug that has received authorization from European Commission and approval from the U.S. Food and Drug Administration for treatment of coronavirus disease 2019 (Covid-19). This study, describes, for the first time, the synthesis of a novel charge transfer complex (CTC) between REM, as electron donor, with chloranilic acid (CLA), as π electron acceptor. The CTC was characterized using different spectroscopic and thermogravimetric techniques. UV-visible spectroscopy ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 3.33 × 103 L mol-1 cm-1 and its band gap energy was 1.91 eV. The stoichiometric ratio of REM:CLA was found to be 1:1. The association constant of the complex was 1.11 × 109 L mol-1, and its standard free energy was 5.16 × 104 J mole-1. Computational calculation for atomic charges of energy minimized REM was conducted, the site of interaction on REM molecule was assigned and the mechanism of the reaction was postulated. The solid-state CTC was further characterized by FT-IR and 1H NMR spectroscopic techniques. Both FT-IR and 1H NMR confirmed the formation of the CTC and its structure. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for REM. The assay limits of detection and quantitation were 3.57 and 10.83 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of REM in its bulk form and pharmaceutical formulation (injection). This assay is simple, economic, and more importantly, has high throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of REM's bulk form and pharmaceutical injection.

A Validated LC-MS/MS Assay for the Simultaneous Quantification of the FDA-Approved Anticancer Mixture (Encorafenib and Binimetinib): Metabolic Stability Estimation.

The concurrent use of oral encorafenib (Braftovi, ENF) and binimetinib (Mektovi, BNB) is a combination anticancer therapy approved by the United States Food and Drug Administration (USFDA) for patients with BRAFV600E/V600K mutations suffering from metastatic or unresectable melanoma. Metabolism is considered one of the main pathways of drug elimination from the body (responsible for elimination of about 75% of known drugs), it is important to understand and study drug metabolic stability. Metabolically unstable compounds are not good as they required repetitive dosages during therapy, while very stable drugs may result in increasing the risk of adverse drug reactions. Metabolic stability of compounds could be examined using in vitro or in silico experiments. First, in silico metabolic vulnerability for ENF and BNB was investigated using the StarDrop WhichP450 module to confirm the lability of the drugs under study to liver metabolism. Second, we established an LC-MS/MS method for the simultaneous quantification of ENF and BNB applied to metabolic stability assessment. Third, in silico toxicity assessment of ENF and BNB was performed using the StarDrop DEREK module. Chromatographic separation of ENF, BNB, and avitinib (an internal standard) was achieved using an isocratic mobile phase on a Hypersil BDS C18 column. The linear range for ENF and BNB in the human liver microsome (HLM) matrix was 5-500 ng/mL (R2 ≥ 0.999). The metabolic stabilities were calculated using intrinsic clearance and in vitro half-life. Furthermore, ENF and BNB did not significantly influence each other's metabolic stability or metabolic disposition when used concurrently. These results indicate that ENF and BNB will slowly bioaccumulate after multiple doses.

Experimental and Computational Evaluation of Chloranilic Acid as an Universal Chromogenic Reagent for the Development of a Novel 96-Microwell Spectrophotometric Assay for Tyrosine Kinase Inhibitors.

The tyrosine kinase inhibitors (TKIs) are chemotherapeutic drugs used for the targeted therapy of various types of cancer. This work discusses the experimental and computational evaluation of chloranilic acid (CLA) as a universal chromogenic reagent for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for TKIs. The reaction resulted in an instantaneous formation of intensely purple colored products with TKIs. Spectrophotometric results confirmed that the reactions proceeded via the formation of charge-transfer complexes (CTCs). The physical parameters were determined for the CTCs of all TKIs. Computational calculations and molecular modelling for the CTCs were conducted, and the site(s) of interaction on each TKI molecule were determined. Under the optimized conditions, Beer's law correlating the absorbances of the CTCs with the concentrations of TKIs were obeyed in the range of 10-500 µg/well with good correlation coefficients (0.9993-0.9998). The proposed MW-SPA fully validated and successfully applied for the determination of all TKIs in their bulk forms and pharmaceutical formulations (tablets). The proposed MW-SPA is the first assay that can analyze all the TKIs on a single assay system without modifications in the detection wavelength. The advantages of the proposed MW-SPA are simple, economic and, more importantly, have high throughput.

Synthesis, cytotoxic evaluation, and molecular docking studies of novel quinazoline derivatives with benzenesulfonamide and anilide tails: Dual inhibitors of EGFR/HER2.

We synthesized a new series of 2-[(3-(4-sulfamoylphenethyl)-4(3H)-quinazolinon-2-yl)thio]anilide derivatives (2-16) and evaluated their cytotoxic activity against breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), and acute myeloid leukemia (HL-60 and K562) cells. To reveal their selectivity toward cancer cells, the compounds were also tested against the human fibroblast cell line, MRC-5. Compounds 1-5 exhibited potent cytotoxic activity against the tested cell lines with IC50 values of 0.65-3.86, 0.68-4.60, 0.41-1.45, 0.42-4.07, and 3.77-25.55 µM, respectively compared to sorafenib, the standard drug (IC50 2.50, 2.50, and 3.14 µM against MCF-7, HT-29, and HL60 cells, respectively). Interestingly, compounds 1-5 displayed selectivity toward the cancer cell lines over MRC-5 (IC50 3.77-25.55 µM). These compounds also displayed potent inhibitory activity against EGFR and HER2 kinases (IC50 0.09-0.43 and 0.15-0.33 µM, respectively) compared to the standard drug, sorafenib (IC50 0.11 and 0.13 µM, respectively). Likewise, compounds 1, 4, and 5 showed strong inhibitory activity against VEGFR2 (IC50 0.34, 0.28 and 0.39 µM, respectively) compared to sorafenib (IC50 0.17 µM). We also employed molecular docking to identify the structural features required for the EGFR/HER2 inhibitory activity of the new series. Ultimately, compounds 1, 4, and 5 were demonstrated to be candidates for further preclinical investigations.

A reliable and stable method for the determination of foretinib in human plasma by LC-MS/MS: Application to metabolic stability investigation and excretion rate.

Foretinib (GSK1363089) is a multiple receptor tyrosine kinases inhibitor. In this study, a reliable, fast liquid chromatography-tandem mass spectrometric method was described for assaying foretinib in plasma, urine, and rat liver microsome samples. Simple extraction procedure by protein preciptation with acetonitrile was implemented for foretinib and brigatinib (internal standard) analysis. Chromatographic resolution of analytes was achieved on C18 column with the help of isocratic mobile phase. The binary mobile phase consisted of 60% ammonium formate (10 mM, pH 4.2) and 40% acetonitrile at a flow rate of 0.25 mL/min. Run time was 3 min, and both foretinib and brigatinib were eluted within 0.74 and 1.95 min; they were detected in positive ion mode utilizing multiple reactions monitoring mode. Linearity of the proposed method ranged from 5 to 500 ng/mL (r2 ≥ 0.9993) in the human plasma. Lower limit of quantification and detection were 6.0 and 1.8 ng/mL, respectively. Intraday and interday precision and accuracy were 0.16 to 1.67 % and -2.39 to -0.52 %. In vitro half-life and intrinsic clearance were 24.93 min and 6.56 mL/min/kg, respectively. Literature review showed that no previous studies have been proposed for the analytical quantification of foretinib in human plasma or its metabolic stability. The established method was also applied to estimate the rate of foretinib excretion in rat urine. The developed method can be used for foretinib pharmacokinetic applications.

A highly efficient and sensitive LC-MS/MS method for the determination of afatinib in human plasma: application to a metabolic stability study.

Afatinib (AFT) is a new tyrosine kinase inhibitor approved for the treatment of nonsmall cell lung cancer. In the present study, a simple, specific, rapid and sensitive liquid chromatography tandem mass-spectrometric method for the quantification of AFT in human plasma, was developed and validated. Chromatographic separation of the analytes was accomplished on a reversed-phase Luna(®) -PFP 100 Å column (50 × 2.0 mm; 3.0 µm) maintained at ambient temperature. Isocratic elution was carried out using acetonitrile-water (40:60, v/v) containing 10 mm ammonium formate buffer (pH 4.5) adjusted with formic acid at a flow rate of 0.4 mL min(-1) . The analytes were monitored by electrospray ionization in positive ion multiple reaction monitoring mode. The method yields a linear calibration plot (r(2) = 0.9997) from a quantification range of 0.5-500 ng mL(-1) with the lower limit of quantification and lower limit of detection of 1.29 and 0.42 ng mL(-1) , respectively. The intra- and inter-day precision and accuracy were estimated and found to be in the ranges of 1.53-4.11% for precision and -2.80-0.38% for accuracy. Finally, quantification of afatinib in a metabolic stability study in rat liver microsomes was achieved through the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.

Design, synthesis, characterization of novel ruthenium(II) catalysts: highly efficient and selective hydrogenation of cinnamaldehyde to (E)-3-phenylprop-2-en-1-ol.

In this contribution, two novel supported and non-supported ruthenium(II) complexes of type [RuCl2(dppme)(NN)] where [dppme is H2C=C(CH2PPh2)2 and NN is N1-(3-(trimethoxysilyl)propyl)ethane-1,2-diamine] were prepared. The NN co-ligand caused release of one of the dppme ligands from [RuCl2(dppme)2] precursor to yield complex 1. The process of substitution of dppme by NN was monitored by 31P{1H}-NMR. Taking advantage of the presence of trimethoxysilane group in the backbone of complex 1, polysiloxane xerogel counterpart, X1, was prepared via sol-gel immobilization using tetraethoxysilane as cross-linker. Both complexes 1 and X1 have been characterized via elemental analysis, CV and a number of spectroscopic techniques including FT-IR, 1H-, 13C-, and 31P-NMR, and mass spectrometry. Importantly, carbonyl selective hydrogenation was successfully accomplished under mild conditions using complex 1 as a homogenous catalyst and X1 as a heterogeneous catalyst, respectively.

A One-Step Green Microwell Spectrophotometric Assay for the Determination of Certain New Chemotherapeutic Drug Formulations.

BACKGROUND: The formation of charge transfer complexes (CTCs) of iodine with five chemotherapeutic drugs used for the treatment of different types of cancer has not been investigated. These drugs were olaparib, seliciclib, vandetanib, dasatinib, and tozasertib. Additionally, these drugs need an appropriate general spectrophotometric assay for their analysis in the dosage forms regardless of the differences in their chemical structures. OBJECTIVE: The aim of this study was the development of a novel microwell spectrophotometric assay (MW-SPA) for one-step determination of these drugs via their intereactions with iodine resulted in instantaneous producing a bright lemon yellow-colored CTCs. METHODS: The spectrophotometric study of the CTCs were conducted, and all CTCs were characterized. Site(s) of interaction on each drug were assigned, and the MW-SPA was developed and applied to the analysis of dosage forms. RESULTS: The findings confirmed that the reactions proceeded via CTCs formation. Beer's law was obeyed over a general concentration range of 1-6 µg/mL. The limits of detection and quantitation were in the ranges of 0.5-2.1 and 1.5-6.4 µg/mL, respectively. The proposed MW-SPA demonstrated excellent precisions as the relative standard deviations were < 2.24 and 2.23% for the intra- and inter-assay precision, respectively. Recovery studies demonstrated the accuracy of MW-SPA. Successful determination of all drugs in bulk and tablet forms was achieved using the MW-SPA. The environmental sustainability of the proposed methodology was determined, providing evidence of the assay's alignment with the basis of green analytical chemistry. The high throughput of the assay was documented. CONCLUSIONS: In contrast to other existing methods, the MW-SPA described herein valid for analyzing all drugs at the same wavelength. HIGHLIGHTS: The assay is useful for routine analysis of drugs in their formulations in quality control laboratories.

Systematic Engineering of Near-Infrared Small Molecules Based on 4H-Cyclopenta[1,2-b:5,4-b']dithiophene Acceptors for Organic Solar Cells.

Nonfullerene acceptors (NFAs) have emerged as tremendous materials, efficiently advancing bulk-heterojunction organic solar cells (OSCs) technology. Unlike their fullerene counterparts, NFAs offer the unique advantage of finely tunable electronic energy levels and optical characteristics, which correspond to substantial enhancement in power conversion efficiency of OSCs. Herein, we have introduced a new series of near-infrared NFAs (AY1-AY8) to advance this technology further. Our research deeply investigates the structure-property relationship and thoroughly explores the optical, optoelectronics, photophysical, and photovoltaic characteristics of a synthetic reference molecule (R) and the modeled AY1-AY8 NFAs series. We performed advanced quantum chemical simulations using density functional theory (DFT) and time-dependent DFT methods. Additionally, we also estimated key geometric characteristics such as frontier molecular orbitals, hole-electron overlap, density of states, molecular electrostatic potential, molecular excitation and binding energies, transition density matrix, and reorganizational energy of electrons and holes and compared them with those of a synthetic reference molecule (R). Our findings show that all designed materials (AY1-AY8) exhibit red-shift absorption, improved electronic charge mobility, and low binding and excitation energies compared to R. Notably, these designed materials (AY1-AY8) display significantly narrower electronic energy gaps (E g 1.89-1.71 eV), indicating enhanced charge shifting from the highest occupied molecular orbital to lowest unoccupied molecular orbital and broadening of the absorption spectrum. Moreover, we also revealed a comprehensive study of the donor/acceptor complex of PTB7-Th/AY8 to understand charge shifting between donor and acceptor molecules. Therefore, we strongly recommend this designed (AY1-AY8) series to the experimentalists for the future development of highly efficient OSC devices.

Exploring HCl-HCl interactions: QZVPP calculations, improved Lennard-Jones potential, and second virial coefficient analysis for thermodynamics and industrial applications.

In this paper, we present a comprehensive analysis of HCl-HCl interactions, including QZVPP calculations, energy fitting, conformation validation, and the determination of the second virial coefficient B using improved Lennard-Jones (ILJ) potential parameters. To acquire accurate interaction energies, initial QZVPP calculations are performed on approximately 1851 randomly generated HCl-HCl conformations. Then, these energies are used to fit an improved Lennard-Jones potential energy surface, allowing for a robust description of HCl-HCl interactions. The ILJ potential parameters are then used to validate particular HCl dimer conformations, ensuring their stability and consistency with experimental observations. The correlation between calculated and experimental conformations strengthens the validity of the ILJ potential parameters. In addition, the second viral coefficient B is calculated at various temperatures using the ILJ potential. The obtained B values are compared to experimental data, demonstrating close agreement, and validating the ILJ potential's ability to accurately capture the intermolecular interactions and gas-phase behavior of the HCl-HCl system. The results of this study demonstrate the effective implementation of QZVPP calculations, energy fitting, and ILJ potential parameters in validating HCl-HCl conformations and accurately determining the second virial coefficient B. The high degree of concordance between calculated B values and experimental data demonstrates the validity of the ILJ potential and its suitability for modeling HCl-HCl interactions. This research contributes to a greater comprehension of HCl-HCl interactions and their implications for numerous chemical and atmospheric processes. The validated conformations, energy fitting method, and calculated second virial coefficients provide valuable instruments for future research and pave the way for more accurate modeling and simulations of HCl-HCl systems.

Advancing optoelectronic characteristics of Diketopyrrolopyrrole-Based molecules as donors for organic and as hole transporting materials for perovskite solar cells.

A stable and efficient hole-transport material (HTM) is crucial for high-performance perovskite solar cells (PSCs). A 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro-MeOTAD) being used widely to prepare highly efficient PSCs. However, Spiro-MeOTAD has some limitations due to its complex synthesis, which increases its cost, and it also requires dopants to improve its performance. Therefore, we designed thirteen unique small-molecule-based HTMs (MK1-MK13), which are easy to synthesize, highly cost-effective, and don't require dopants to prepare efficient PSCs. Their electrical and optical properties are then investigated theoretically using advanced quantum chemical approaches. The designed molecules showed lower energy gaps and improved optical and optoelectronic characteristics because of the improved phase inversion geometry. The detailed photo-physical and optoelectronic characteristics have been studied using density functional theory (DFT) and time-dependent (TD-DFT) calculations. Moreover, we investigated the impact of holes and electrons and the density of states, open-circuit voltage, frontier molecular orbital, transition density matrix, and other structural and photovoltaic characteristics of these materials. Among these, the MK3 molecule possesses the much narrower optical band gap of 1.04 eV and absorbance (λ max) of 684 nm, respectively. In addition, a profound investigation of the MK3/PC61BM blend shows excellent charge transfer at the acceptor-donor interface. Therefore, our proposed technique is necessary for generating appropriate photovoltaic materials for efficient optoelectronic devices and is helpful in further advancing the field.

Identification of novel benzothiazole-thiadiazole-based thiazolidinone derivative: in vitro and in silico approaches to develop promising anti-Alzheimer's agents.

Aim: The present study describes benzothiazole derived thiazolidinone based thiadiazole derivatives (1-16) as anti-Alzheimer agents. Materials & methods: Synthesis of benzothiazole derived thiazolidinone based thiadiazole derivatives was achieved using the benzothiazole bearing 2-amine moiety. These synthesized compounds were confirmed via spectroscopic techniques (1H NMR, 13C NMR and HREI-MS). These compounds were biologically evaluated for their anti-Alzheimer potential. Binding interactions with proteins and drug likeness of the analogs were explored through molecular docking and ADMET analysis, respectively. In the novel series, compound-3 emerged as the most potent inhibitor when compared with other derivatives of the series. Conclusion: The present study provides potent anti-Alzheimer's agents that can be further optimized to discover novel anti-Alzheimer's drugs.

[Box: see text].