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Background: Carbon quantum dots (CQDs) have gained much interest recently for being efficient probes. Their cost-effectiveness, eco-friendliness, and unique photocatalytic activities made them distinctive alternatives to other luminescent approaches like fluorescent dyes and luminous derivatization. Meanwhile, delafloxacin (DLF) is a recently approved antibacterial medicine. DLF has been authorized for the treatment of soft-tissue and skin infections as well as pneumonia. Therefore, new eco-friendly, cost-effective, and sensitive tools are needed its estimation in different matrices., Results: In the proposed study, green copper and nitrogen carbon dots (Cu-N@CDs) were synthesized from a green source (plum juice with copper sulphate). Cu-N@CQDs were then characterized using multiple tools including X-ray photon spectroscopy (XPS), FTIR and UV-VIS spectroscopy, Zeta potential measurements, High-resolution transmission electron microscopy (HRTEM), and fluorescence spectroscopy. After gradually adding DLF, the developed quantum dots' fluorescence was significantly enhanced within the working range of 0.5-100.0 ng mL -1 . The limits of detection and quantification were 0.08 and 0.27 ng mL -1 , respectively. The accuracy of the proposed method ranged from 96.00 to 99.12 % in recovery%, when recovered from milk and plasma samples., Significance: Cu-N@CDs were utilized and validated for selectively determining DLF in several matrices including pharmaceutical forms, human plasma and in milk samples using spectrofluorimetric technique. The bio-analytical method is simple and could be used in content uniformity testing as well as in therapeutic drug monitoring in human plasma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study employed functional principal component analysis (FPCA) and covariate design of experiments (DoE) to mitigate the susceptibility of chemometric methods to unexpected variations stemming from operational and instrumental factors. A comparative analysis with partial least squares (PLS) revealed that our proposed approach effectively reduced variability across different analysts, days, and instruments. Specifically, FPCA was utilized to compress available spectral wavelength information, while covariate DoE aided in selecting an optimal training set within the experimental space. Subsequently, PLS was applied for the simultaneous determination of tadalafil (TD) and dapoxetine hydrochloride (DP) in their binary mixture. Validation of the proposed method through accuracy profiles demonstrated its reliability, paving the way for its application in pharmaceutical analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Avapritinib (AVA) is the first medication authorized by the US-FDA in 2020 for the management of gastrointestinal stromal tumours (GISTs) that can't be treated by surgery. Cancer is among the most common causes of death worldwide and is the second most common cause of death after cardiovascular disease. Therefore, a quick, easy, sensitive, and straightforward fluorimetric approach was used to analyse AVA in pharmaceutical materials and blood plasma (pharmacokinetic). The suggested technique relies on 2% sodium dodecyl sulphate (SDS, pH 4) micellar system augmentation of the fluorescence of the tested drug. The technique demonstrated high relative fluorescence intensity (RFI) at 430 nm after excitation at 340 nm. Concentrations ranging from 20.0-400.0 ng mL -1 with a limit of quantitation of 9.47 ng mL -1 were used to obtain luminescence data for the studied medicine. In addition, the quantum yield of the AVA fluorescence was increased with the gradual addition of a surfactant at a concentration above its critical micellar level. This knowledge has been exploited to enhance the effectiveness of a spectrofluorometric technique for the estimation of AVA in human plasma (98.95 ± 1.22%) and uniformity tests with greenness assessments. The conditions for enhanced fluorescence were optimized and fully validated using US-FDA and International Conference on Harmonization (ICH) rules. This innovative strategy was expanded for AVA stability research in human plasma across various circumstances. This approach is an eco-friendly solution compared to traditional testing methods that use hazardous chemicals., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Terbium- and nitrogen-doped carbon quantum dots (Tb,N@CQDs) were greenly created employing microwave synthesis from plum juice with terbium nitrate. The synthesis of Tb,N@CQDs was fast (7 min) with a high quantum yield (35.44%). Tb,N@CQDs were fully characterized using transmission electron microscopy, Zeta potential analysis, fluorescence, and ultraviolet spectroscopy. Omadacycline (OMC) is a broad-spectrum tetracycline that has been recently approved by the United States Food and Drug Act (FDA) in October 2018. OMC is the first oral aminomethylcycline class antibiotic drug that was authorized for the treatment of acute skin structure infections and community-acquired pneumonia. Tb,N@CQDs exhibited emission at 440 nm after excitation at 360 nm, where their fluorescence intensity showed a reduction upon addition of OMC. The experimental parameters were further studied and optimized. The linear range was between 40 and 60 parts per billion (ppb), with (limit of quantitation) equal to 34.78 ppb. The proposed approach was validated for bioanalytical purposes using FDA guidelines and proved to be straightforward, cheap, highly sensitive, and very selective, which can be used in clinical studies. The developed approach proved to be green using some current assessment metrics and was applied successfully for the determination of OMC in human plasma, milk, and pharmaceutical formulations as well as pharmacokinetic study., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Avapritinib (AVP) was the first precision drug to be approved by the US Food and Drug Administration (FDA) in 2020 for patients suffering from metastatic gastrointestinal stromal tumors (GISTs) and progressive systemic mastocytosis. The analysis of AVP in pharmaceutical tablets and human plasma was then carried out using a fast, efficient, sensitive, and simple fluorimetric method using a fluorescamine reagent. The procedure is based on the interaction between fluorescamine as a fluorogenic reagent and the primary aliphatic amine moiety in AVP using borate buffer solution at pH 8.8. The produced fluorescence was measured at 465 nm (Excitation at 395 nm). The calibration graph's linearity range was discovered to be 45.00-500.0 ng mL -1 . Utilizing the International Council for Harmonization (ICH) and US-FDA recommendations, the research technique was validated and bioanalytically validated. The proposed approach was effectively employed for determining the stated pharmaceuticals in plasma with a high percentage of recovery ranging from 96.87 to 98.09 and pharmaceutical formulations with a percentage of recovery equal to 102.11% ± 1.05%. In addition, the study was extended to a pharmacokinetic study of AVP with 20 human volunteers as a step for AVP management in therapeutic cancer centers., (© 2023 John Wiley & Sons Ltd.)

Copper (Cu) plays a role in maintaining healthy nerve cells and the immune system. Osteoporosis is a high-risk factor for Cu deficiency. In the proposed research, unique green, fluorescent cysteine-doped MnO 2 quantum dots (Cys@MnO 2 QDs) were synthesized and assessed for the determination of Cu in different food and hair samples. The developed quantum dots were synthesized with the help of cysteine using a straightforward ultrasonic approach to create 3D fluorescent Cys@MnO 2 QDs. The resulting QDs' morphological and optical characteristics were carefully characterized. By adding Cu ions, the intensity of fluorescence for the produced Cys@MnO 2 QDs was found to be dramatically reduced. Additionally, the applicability of Cys@MnO 2 QDs as a new luminous nanoprobe was found to be strengthened by the quenching effect grounded on the Cu-S bonding. The concentrations of Cu 2+ ions were estimated within the range of 0.06 to 7.00 µg mL -1 , with limit of quantitation equal to 33.33 ng mL -1 and detection limit equal to 10.97 ng mL -1 . The Cys@MnO 2 QD technique was applied successfully for the quantification of Cu in a variety of foods, including chicken meat, turkey, and tinned fish, as well as in human hair samples. The chance that this novel technique could be a useful tool for figuring out the amount of cysteine in bio-samples is increased by the sensing system's remarkable advantages, which include being rapid, simple, and economical., (© 2023. The Author(s).)

The endemicity of the pandemic coronavirus disease 2019 (COVID-19) infection proved to be transitional only. Spikes are forming again in 2023, and high expectations are returning for reinfections and viral mutations. Molnupiravir (MOL) has been approved as an oral antiviral drug for the treatment of the COVID-19 causative virion. Therefore, the development of an ultrasensitive, instantaneous, and cost-effective method for the quantification of MOL in real plasma samples and formulated dosage form are mandatory. The proposed approach is based on the synthesis of a MOL metal-chelation product. MOL as a ligand was chelated with 1.0 mM zinc(II) in an acetate buffer (pH 5.3). After illumination at 340 nm, the intensity of the MOL fluorescence measured at 386 nm was increased by about 10-fold. The linearity range was found to be from 60.0 to 800.0 ng mL -1 with limit of quantitation (LOQ) of 28.6 ng mL -1 . Two methods were utilized for measuring the greenness of the proposed method (Green Analytical Procedure Index [GAPI] and analytical greenness metric [AGREE] methods), with results equal to 0.8. The binding stoichiometry of MOL with the zinc(II) ion was found to be 2:1. All the experimental parameters were optimized and validated using International Conference on Harmonization (ICH) and United States Food and Drug Administration (US-FDA) recommendations. Furthermore, the fluorescent probes were successfully utilized in real human plasma with high percentages of recovery (95.6%-97.1%) without any matrix interferences. The mechanism of fluorescent complex formation was confirmed using 1 H NMR in the presence and absence of Zn(II). The method was further utilized for testing content uniformity of MOL in its marketed capsule dosage forms., (© 2023 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a-mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine. The enzymatic assay revealed that3e,3d, and3ihad goodtubulin polymerization inhibition (IC 50  = 5.3, 8.6, and 8.05 µM, respectively) compared to the reference Combretastatin A4 (IC 50  = 2.15 µM). Moreover,3e,3l, and3fexhibited EGFR inhibition (IC 50  = 0.097, 0.154, and 0.334 µM, respectively) compared to Erlotinib (IC 50  = 0.056 µM). Compounds3eand3fwere investigated for their effects on the cell cycle, apoptosis induction, andwnt1/β-cateningene suppression. The apoptosis markers Bax, Bcl2, Casp3, Casp9, PARP1, and β-actin were detected by Western blot. In-silico molecular docking, physicochemical, and pharmacokinetic studies were implemented for the validation of dual mechanisms and other bioavailability standards. Hence, Compounds3eand3fare promising antiproliferative leads with tubulin polymerization and EGFR kinase inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The neuro-stimulant anti-narcoleptic drug as modafinil (MOD) is used to treatment neurological conditions caused by COVID-19. MOD was used to treatment narcolepsy, shift-work sleep disorder, and obstructive sleep apnea-related sleepiness. So, an innovative, quick, economical, selective, and ecologically friendly procedure was carried out. A highly sensitive N@CQDs technique was created from green Eruca sativa leaves in about 4 min using microwave synthesis at 700 w. The quantum yield of the synthesized N@CQDs was found to be 41.39%. By increasing the concentration of MOD, the quantum dots' fluorescence intensity was gradually quenched. After being excited at 445 nm, the fluorescence reading was recorded at 515 nm. The linear range was found to be in the range 50 - 700 ng mL -1 with lower limit of quantitation (LOQ) equal to 45.00 ng mL -1 . The current method was fully validated and bio analytically according to (US-FDA and ICH) guidelines. Full characterization of the N@CQDs has been conducted by high resolution transmission electron microscope (HRTEM), Zeta potential measurement, fluorescence, UV-VIS, and FTIR spectroscopy. Various experimental variables including pH, QDs concentration and the reaction time were optimized. The proposed study is simply implemented for the therapeutic drug monitoring system (TDMS) and various clinical laboratories for further pharmacokinetic research., (© 2022. The Author(s).)

An innovative polymer-based electro-sensor decorated with Tb nanoparticles has been developed for the first time. The fabricated sensor was utilized for trace determination of favipiravir (FAV), a recently US FDA-approved antiviral drug for the treatment of COVID-19. Different techniques, including ultraviolet-visible spectrophotometry (UV-VIS), cyclic voltammetry (CV), scanning electron microscope (SEM), X-ray Diffraction (XRD) and electrochemical impedance spectroscopy (EIS), were applied for the characterization of the developed electrode Tb NPs @ poly m-THB/PGE. Various experimental variables, including pH, potential range, polymer concentration, number of cycles, scan rate and deposition time, were optimized. Moreover, different voltammetric parameters were examined and optimized. The presented SWV method showed linearity over the range of 10-150 × 10 -9 M with a good correlation coefficient (R = 0.9994), and the detection limit (LOD) reached 3.1 × 10 -9 M. The proposed method was applied for the quantification of FAV in tablet dosage forms and in human plasma without any interference from complex matrices, obtaining good % recovery results (98.58-101.93%)., Competing Interests: The authors declare no conflict of interest.

Vonoprazan (VON) has been approved recently via US-FDA in 2015 as the first in class of potassium competitive acid blocker group. VON is used for management of GIT ulcer, reflux esophagitis and for eradication of Helicobacter pylori. So, the first spectrofluorimetric method was developed for estimation of VON in real human plasma and content uniformity test. The fluorimetric methodology based on reaction of secondary amine group in VON with benzofurazan (0.05% w/v NBD-Cl) reagent as nucleophilic substitution reaction in alkaline medium (0.1 M borate buffer pH 8.2) to produce highly fluorescent product measure at 530 nm after excitation at 465 nm. The linear calibration range was found 15 to 200 ng mL -1 with lower limit of quantitation (LOQ) equal to 8.57 ng mL -1 . The method was successfully applied for estimation of VON in pharmacokinetic (PK) and content uniformity studies. The maximum plasma concentration was found to be (C max ) 71.03 ng mL -1 after maximum time (t max ) equal to 1.5 ± 0.15 h. The presented strategy also applied to ensure concentration of drug in each tablet using content uniformity test with high percent of recovery 100.05 ± 0.66. The proposed method was established for clinical laboratories and therapeutic drug monitoring studies., (© 2022. The Author(s).)

Elagolix (ELX) is an orally administered non-peptidic GnRH antagonist that has been approved by the Food and Drug Administration in 2018 for the treatment of endometriosis pain. A sensitive and selective method for estimating elagolix (ELX) in human plasma and content uniformity was developed and validated. The spectrofluorimetric technique was used to investigate ELX utilizing boron-doped carbon quantum dots (B@CQDs). After gradually adding ELX, the quantum dots fluorescence was enhanced with LOQ of 1.74 ng mL -1 , the calibration curve between ELX and corresponding fluorescence intensity was found over a range of 4-100 ng mL -1 . The method was successfully applied in real human plasma with pharmacokinetic study and content uniformity test. The pharmacokinetic parameters as C max were found to be 570 ± 5.32 ng. mL -1 after 1 h, t 1/2 was found to be 6.50 h, and AUC was found to be 1290 ± 30.33 ng. h. mL -1 . B@CQDs were characterized using variety of instruments. The strategy is simple to implement in clinical labs and therapeutic drug monitoring systems., (© 2022. The Author(s).)

Tyramine (TYM) is catecholamine releasing compound and TYM rich food causes hypertensive crisis due to a combination with monoamine oxidase inhibitor (MAOIs). Therefore, analysis of TYM in TYM rich food as (old cheese, cured meat, sausage, pickled olive and canned fish) and the environment is essential for hypertensive patients and to improvement of food industries. In this work, TYM was analyzed in different types of food using novel green synthesis carbon dots from Ficus carica (fig fruits). The gradual addition of TYM to polyamine carbon quantum dots (PA@CQDs) led to enhancement of the quantum dots fluorescence due to formation of hydrogen bonding between quantum dots and TYM. The calibration graph was plotted in the range 5-400 ng mL -1 . The method was applied for the determination of TYM in different types of food as old cheese, cured meat, sausage, pickled olive and canned fish. The lower limit of quantitation (LOQ) was found to be 1.68 ng mL -1 . The method was successfully applied for the quantification of TYM in varying types of food with high sensitivity and high economic effect due to the reusability of the quantum dots. The optical and morphological characters of quantum dots were studied carefully., (© 2022 John Wiley & Sons Ltd.)

Favipiravir, molnupiravir, and ritonavir have been recently approved as the first oral antivirals for treatment of SARS-CoV-2 viral infections. Their combination was reported in several clinical studies, alternatively, to enhance the viral eradication and improve patient's recovery times and rates. Being all orally administered, therefore, the development of new sensitive and validated methodologies for their simultaneous determination is a necessitate. In the proposed research, a sensitive, selective, and simple high-performance thin layer chromatography method was developed and validated for determination of favipiravir, molnupiravir, and ritonavir. Silica gel 60F254 thin layer chromatography plates were used as stationary phase for this separation using mobile phase composed of methylene chloride:ethyl acetate:methanol:25% ammonia (6:3:4:1, v/v/v/v). Densitometric detection was performed at wavelength 289 nm. Peaks of favipiravir, molnupiravir, and ritonavir were resolved at retention factors 0.22, 0.42, and 0.63, respectively. The proposed method was found linear within the specified ranges of 3.75-100.00 μg/mL for molnupiravir and favipiravir, and 2.75-100.00 μg/mL for ritonavir. Limits of detection were found to be 1.12, 1.21, and 0.89 μg/mL for favipiravir, molnupiravir, and ritonavir, respectively. This is the first method to be reported for the simultaneous determination of the cited three antiviral drugs. The method was assessed on novel greenness metrics., (© 2022 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.)

The COVID-19 pandemic has encouraged the search for novel antiviral medications. Recently, molnupiravir (MOL) has been approved as an oral antiviral to manage COVID-19. Thus, the development of sensitive and cost-effective methods for quantification of MOL in real plasma samples (pharmacokinetic) and pharmaceutical tablets is required. Herein, we present the fabrication of novel fluorescent polyamine quantum dots (PA@CQDs) fabricated from apricots using one step synthesis for analysis of MOL. The relative fluorescence intensity (RFI) of the synthesized quantum dots was influentially quenched by the addition of molnupiraivr. The linear range was found to be between 2-70 ng mL -1 with lower limit of quantitation (LOQ) equal to 1.61 ng mL -1 . The fluorescent probe was successfully utilized in a pharmacokinetic study of MOL with maximum plasma concentration ( C max ) 920.2 ± 6.12 ng mL -1 without any matrix interference. The sensitivity and selectivity of the presented method allow its application in clinical laboratories., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ertapenem (EPM) has been recently approved by the United States Food and Drug Administration (US-FDA) as an antimicrobial drug. EPM has a broad spectrum of action against different bacterial strains and is most commonly prescribed in Egypt for the treatment of Klebsiella pneumonia. In this study, EPM was estimated using a sensitive and selective spectrofluorimetric method for human plasma and pharmaceutical vials. The measured fluorescence (at 540 nm) was obtained from reaction of EPM with 0.05% w/v benzofurazan (NBD-Cl) using 0.1 M borate buffer pH 8.8 after excitation at 460 nm. The fluorometric linear range was stable from 10 to 350 ng ml -1 . The lower limit of detection and the lower limit of quantitation were found to be 2.13 and 6.47 ng ml -1 respectively. Many factors such as pH, temperature, heating time, and NBD-Cl concentration were optimized. The presented work was validated according to International Council for Harmonisation guidelines and bio-analytically validated using FDA recommendations. The significant finding of this study, sensitivity, was successfully applied in Egypt for a pharmacokinetic application and commercial vials. Pharmacokinetic parameters were studied and the result, recorded as C max of EPM, was found to be 83.60 μg ml -1 after infusion of 0.5 g of Invanz® for 30 min. AUC 0-∞ was found to be 320 ± 30.2 μ.h ml -1 ., (© 2022 John Wiley & Sons, Ltd.)

Background: Silver nanoparticles synthesis is now widely applicable as a method for sensitive spectrophotometric determination of many pharmaceuticals., Objective: A highly sensitive, cheap, green, nonextractive, and accurate spectrophotometric method was developed for the determination of three important antiviral drugs., Methods: The method depends on the formation of silver nanoparticles as a result of the redox reaction between antiviral drugs as a reducing agent and AgNO3 as an oxidizing agent in presence of polyvinyl pyrrolidone as a stabilizing agent. The UV absorbance of the resulted golden yellow silver nanoparticles can be easily measured at 421 nm for Sofosbuvir (SFS) and Ritonavir (RIT) and at 425 nm for Lamivudine (LAM)., Results: The LODs were 23.5, 30, and 21.5 nm/mL for SFS, LAM, and RIT, respectively. The LOQs were 70.5, 90, and 64.6 nm/mL for SFS, LAM, and RIT, respectively. The method was validated according to International Conference on Harmonization guidelines, and it was successively applied for the determination of the studied drugs in their different pharmaceutical dosage forms and gave excellent percent of recovery. The results showed excellent agreement with the reported method with respect to precision and accuracy., Conclusions: Being simple, fast, robust, and economic, this method is eligible for use in the routine work in pharmaceutical quality control laboratories., Highlights: A sensitive and economic spectrophotometric method was developed and validated for quantitative determination of SFS, LAM, and RIT. The method was validated and applied for determination of the studied drugs in their different formulations. The method used water as the main solvent, so our proposed method is considered environmentally friendly., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ombitasvir, ritonavir and paritaprevir are three recently discovered directly acting antiviral drugs (DAADs) used in combined single dose tablet dosage form for treatment of hepatitis-C viral infections (HCV). The methods of analysis followed by quality control and research laboratories are required to be economic and fast; however, these methods can also produce huge amounts of chemical waste. In this study two fast, economic and green HPLC and HPTLC methods were validated for the simultaneous determination of the three drugs. For HPLC, isocratic elution used a mixture of micellar aqueous mobile phase consisting of (0.15 M sodium lauryl sulfate and 0.01 M sodium dihydrogen phosphate, pH 6.2) and ethanol (56:44). Elution was done on RP-C18 Kinetix® column (5 μm, 150 mm × 4.6 mm ID) at flow 1 mL min -1 and 254 nm UV-detector. HPTLC separations were performed on Merck® (20 cm × 10 cm) aluminum HPTLC plates coated with silica gel 60F254 using a mobile phase, Methylene chloride: methanol: ethyl acetate: ammonia (25%), (5:1:3:1, v/v/v/v) respectively. The calibration curves were linear across ranges of 3-100 μg mL -1 and 0.1-2 μg/spot for both HPLC and HPTLC methods, respectively. The two methods were applied successfully for the determination of the three drugs under study in their combined tablets dosage forms.

The combination of sofosbuvir and daclatasvir or sofosbuvir and ledipasvir is now widely used as an ideal treatment for hepatitis C virus infection. For this purpose, a simple, sensitive, accurate, economic, and precise high-performance thin-layer chromatography was developed and validated for the determination of sofosbuvir, daclatasvir, and ledipasvir in their pure form as well as their different pharmaceutical products. The method used Merck high-performance thin-layer chromatography aluminum plates precoated with silica gel 60 F254 as a stationary phase and mobile phase consisting of methylene chloride/methanol/ethyl acetate/ammonia (25%) (6:1:4:1, v/v/v/v). This system was found to give compact symmetric peaks of sofosbuvir, daclatasvir, and ledipasvir with retardation factors of 0.27 ± 0.01, 0.50 ± 0.007, and 0.68 ± 0.008, respectively. The densitometric scanner was set at 275 nm using a deuterium lamp. The calibration curves were linear over the range of 100-3000 ng/spot for sofosbuvir, and daclatasvir, and range of 50-3000 ng/spot for ledipasvir. The detection limits were 22.5, 31.90, and 15.80 for sofosbuvir, daclatasvir, and ledipasvir. The quantitation limits were 67.50, 95.60, and 47.50 for sofosbuvir, daclatasvir, and ledipasvir. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines and the results were acceptable., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)