Green Chemistry Metrics Research Articles

Mechanochemical Radical Transformations in Organic Synthesis.

Solid-state radical reactions offer improved green chemistry metrics, better reaction outcomes, and access to intermediates that are difficult or impossible to reach in solution. This minireview explores these reactions in the context of small molecule synthesis, highlighting their emerging role in sustainable chemistry.

Greenness and whiteness appraisal for bioanalysis of quetiapine, levodopa and carbidopa in spiked human plasma by high performance thin layer chromatography.

A sustainable HPTLC-densitometric method was developed for quantitative determination of Quetiapine (QUET), Levodopa (LD) and Carbidopa (CD) in presence of Dopamine (DOP) as an internal standard. This applicable technique was achieved by spiking human plasma and extraction was performed using the protein precipitation approach. The mobile phase used was acetone, dichloromethane, n-butanol, glacial acetic acid and water (3: 2.5: 2: 2: 1.75, by volume). Method validation was done according to US-FDA guidelines and was able to quantify Quetiapine, Levodopa and Carbidopa in the ranges of 100-4000, 200-8000 and 30-1300 ng/mL, respectively. Bioanalytical method validation parameters were assessed for the studied drugs. Finally, the analytical suggested methodology was evaluated using various green and white analytical chemistry metrics and other tools, such as the green solvent selection tool, analytical eco-scale, green analytical procedure index, analytical greenness metric approach and the red-green-blue algorithm tool. The results revealed that the applied analytical method had a minor impact on the environment and is a relatively greener option than other previously reported chromatographic methods.

Behind the scenes of green chemistry: Glories and shadows of atom transfer radical polymerization environmental impact (E-factor)

The paper presents the evaluation of environmental impact (E-factor) as green chemistry metric, calculated for polymer synthesis via one of the most useful tools of macromolecular chemistry, which is atom transfer radical polymerization (ATRP), belonging to the reversible deactivation radical polymerization (RDRP) techniques. For the first time, experimentally determined polymerization yields were included in the calculation, by analyzing the polymer synthesis process using various organic solvents, different methods of regenerating the catalytic complex (meaning ATRP approach), or using the miniemulsion system as eco-friendly reaction medium and presenting the possibility of effective solvent recovery and reuse. The majority of the values of E-factor were below 16, falling within the scope intended for fine chemicals (5–50). The significant and innovative part of the presented research involves verifying the feasibility of using higher concentrations of the dispersed phase in the case of miniemulsion polymerization (increased to as much as 100 % vs. aqueous phase from a typical 20 %), while the use of recycled water allowed a 3-fold reduction in E-factor value. Polymerization in a miniemulsion environment is also attractive due to its low cost, considering the price of distilled water, which is over 580-fold lower than that of DMSO – a typical organic solvent. These observations allow for the reduction of environmental impact and process cost. Importantly, the observed trends in E-factor changes allowed for the identification of ATRP development directions in line with green chemistry and the circular economy.

Synthesis of Pyrrolo [2,1-a]isoquinolines using Cu NPs decorated microcrystalline cellulose in 2-Methyl-THF: A biodegradable heteregeneous nanocatalyst for the sustainable cascade approach

Copper nanoparticles (Cu NPs) supported on microcrystalline cellulose (MCC) serve as an efficient and biodegradable heterogeneous nanocatalyst for the synthesis of pyrrolo [1,2a] isoquinoline under mild and sustainable reaction conditions through a cascade reaction involving condensation, addition, oxidation, and cyclization events. The catalyst underwent thorough characterization via various techniques, including FT-IR, PXRD, XPS, FE-SEM, EDX, TEM, and HR-TEM analysis. Optimized reaction conditions facilitated high-yield production of a diverse range of pyrrolo [1,2a] isoquinolines in 2-Me THF solvent, and the method demonstrated scalability with successful gram-scale synthesis. Notably, the catalyst exhibited reusability for up to five cycles without a significant decrease in activity. This approach aligns with eco-friendly principles, as evidenced by favorable green chemistry metrics for compound 4a, including low process mass intensity (7.83), a minimal environmental impact factor (6.83), a substantial atom economy (67.56 %), efficient reaction mass efficiency (60.76 %), high chemical yield (92.37 %), low mass intensity (1.64), notable mass productivity (60.97 %), considerable carbon efficiency (69.15 %), and optimum efficiency (89.93 %). These results highlight the sustainable and environmentally conscious nature of the developed synthetic methodology.

In-Silico exploration: Unraveling the anti-cancer potential of 8-Nitroquinoline hydrazides

The proliferation of cancer has propelled the scientific community to expedite drug discovery to nullify the threats of cancers on health segment. Addressing the adverse impact of cancer on health necessitates the effective solution. The profound activity of quinoline core appended heterocyclic derivatives against cancer proliferation impacts their significance in cancer pathology. The hydrazides of 8-nitroquinoline derivatives were synthesised, and their structures were characterized through IR, NMR and single crystal XRD techniques. Initially, the theoretical calculations like green chemistry metrics and DFT studies of the 6a-c have successfully elucidated through FMO, molecular reactivity descriptors, MEP mapping approaches. Outcomes of the studies clearly indicate that the synthesised quinoline hydrazides were highly capable to interact with the biological target entities. In-Silico studies explicit the role of organic small molecules and its efficiency to be the potent drug candidates in therapeutics. Computationally the ADMET studies and the molecular docking performance of 6a-c demonstrated to expose the pharmacokinetic behaviour and binding probability assessments with 11 different oncogenic receptors. The compound 6c could be found as favourable drug molecule adhered from its drug likeness, which comply with most of the ADMET properties. Moreover notably, methyl substituted 6c exhibits its potential binding efficiency with CDK2 and PI3K macromolecules bearing -8.7 & -7.5 kcal/mol binding affinity over 6a & 6b among the selected oncogenic proteins. The insights of in-silico studies could be validated further through in-vitro and in-vivo wet lab research works.

Robust analytical method for the enantiomeric separation of lurasidone hydrochloride: Integrating analytical quality by design and green chemistry principles

Schizophrenia, affecting approximately 1% of the global population, necessitates effective treatments like Lurasidone (LUR). However, the accurate separation of LUR from its enantiomeric impurities remains a significant challenge in pharmaceutical analysis. This study addresses this issue by developing and validating an optimized HPLC method for the simultaneous determination of LUR and its enantiomeric impurity using Analytical Quality by Design (AQbD) principles. The separation was achieved on a Chiralcel OD-H column with isocratic elution employing a hexane-ethanol mixture (92:8, v/v) at a flow rate of 0.9 mL/min, UV detection at 215 nm, and a column temperature of 32 °C. The method was validated using accuracy profiles. Environmental sustainability was assessed using various Green Analytical Chemistry (GAC) metrics, demonstrating favorable greenness attributes. This methodological framework not only enhances pharmaceutical quality control but also promotes sustainability in analytical practices, supporting its application in drug manufacturing and regulatory compliance.

Application of Fe3O4@MCC Nanoparticles as a Heterogeneous Catalyst for Sustainable Multicomponent Synthesis of 2,3′‐Biindoles

AbstractDeveloping innovative methods for synthesizing unique 2,3'‐biindole derivatives is crucial for the progression of drug and material discovery. The use of transition‐metal‐catalyzed coupling improves the efficiency and structural diversity in the synthesis of biindoles. Among these methods, heterogeneous catalysis, particularly using Fe3O4 nanocatalyst supported by microcrystalline cellulose (MCC), is promising for green chemistry applications. In the present work, sixteen 2,3'‐biindole derivatives (4a‐p) were prepared using Fe3O4@MCC nanocatalyst which demonstrated enhanced performance, cost‐effectiveness, and reusability. The magnetic properties of the catalyst enable easy separation, simplifying purification processes, and enhancing overall reaction efficiency to 78%–93%. This method aligns with sustainable chemical practices and offers practical benefits for various industrial applications. This environment friendly method boasts several advantages and demonstrates excellent green chemistry metrics, including process mass intensity, environmental impact factor, atom economy, and reaction mass efficiency, atom economy, carbon efficiency, chemical yield, and optimum efficiency.

Utilizing erythrosine B absorption spectrum shifts for quantitative determination of octreotide and bromocriptine in their pure forms and pharmaceutical formulations. Evaluation of the method greenness

In the present study, two drugs for treating acromegaly are investigated which are either synthetic growth hormone inhibiting hormone (GHIH) or dopamine receptor agonist. Octreotide (OCT) and bromocriptine (BCT) were quantified with a quick, simple, and sensitive spectrophotometric approach in their authentic forms and commercial dosage forms. This approach was based upon formation of ion pair complex between erythrosine B and investigated drugs in an aqueous buffered solution. For OCT determination the higher sensitivity was obtained using ΔA at 525 nm. On the other hand, BCT was estimated using the absorbance at 556 nm. Under optimal conditions for the reaction, construction of calibration curves were performed within concentration range of 0.4–4 µg ml−1 for OCT and 1–9 µg ml−1 for BCT with with low detection limits (0.094 and 0.235 µg ml−1) and low quantitation limits (0.29 and 0.71 µg ml−1) for OCT and BCT respectively. The developed approach was assessed for linearity, accuracy, precision, limits of detection, and limits of quantitation in compliance with ICH validation recommendations. The suggested approaches demonstrated good linearity, as evidenced by determination coefficients (r2) of 0.999 with a slope 0.14 for OCT and 0.9989 with a slope 0.06 for BCT. Additionally, the environmental friendliness of the investigated method was assessed with some of the recent green analytical chemistry metrics.

Unraveling the Potential of Vitamin B3-Derived Salts with a Salicylate Anion as Dermal Active Agents for Acne Treatment.

This study is focused on the utilization of naturally occurring salicylic acid and nicotinamide (vitamin B3) in the development of novel sustainable Active Pharmaceutical Ingredients (APIs) with significant potential for treating acne vulgaris. The study highlights how the chemical structure of the cation significantly influences surface activity, lipophilicity, and solubility in aqueous media. Furthermore, the new ionic forms of APIs, the synthesis of which was assessed with Green Chemistry metrics, exhibited very good antibacterial properties against common pathogens that contribute to the development of acne, resulting in remarkable enhancement of biological activity ranging from 200 to as much as 2000 times when compared to salicylic acid alone. The molecular docking studies also revealed the excellent anti-inflammatory activity of N-alkylnicotinamide salicylates comparable to commonly used drugs (indomethacin, ibuprofen, and acetylsalicylic acid) and were even characterized by better IC50 values than common anti-inflammatory drugs in some cases. The derivative, featuring a decyl substituent in the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water solubility and improved wettability on hydrophobic surfaces, marking it as particularly promising. To investigate the impact of the APIs on the biosphere, the EC50 parameter was determined against a model representative of crustaceans─Artemia franciscana. The majority of compounds (with the exception of the salt containing the dodecyl substituent) could be classified as "Relatively Harmless" or "Practically Nontoxic", indicating their potential low environmental impact, which is essential in the context of modern drug development.

Solvent-Controlled, Atom-Economic, and Highly Regio- and Stereoselective Halo-Chalcogenations of Ynamides: Green Synthesis of Stereodefined Tetrasubstituted Alkenes Bearing Four Different Functional Groups.

The synthesis of stereodefined tetrasubstituted alkenes bearing four different functional groups is challenging. Herein, we disclose a 100% atom-economic and highly regio- and stereoselective halo-chalcogenations, in particular, chlorosulfenylation, bromosulfenylation, chloroselenation, and bromoselenation, of ynamides in toluene at room temperature under an aerobic atmosphere for the synthesis of a wide variety of stereodefined tetrasubstituted alkenes bearing four different functional groups in excellent yields. Notably, all the reactions are highly efficient and furnished the desired products in excellent yield (average yield >96%) and stereoselectivity (Z/E = 90:10 to >99:1) within a short time (15-30 min). Interestingly, the high (Z)-stereoselectivity (syn-addition) is controlled by the solvent. The transformation does not require any catalyst, oxidizing or reducing reagent, or external energy. The products were obtained pure by evaporating the solvent after the reaction and washing the crude product with either pentane or ethanol (column-chromatography-free protocol). Moreover, the solvent toluene was recovered and reused in subsequent reactions, which makes the protocol highly sustainable. The protocol is efficiently scalable (96% yield) on a gram scale. Notably, the products were synthetically diversified to other new classes of stereodefined tetrasubstituted alkenes. Significantly, the green chemistry metrics of the protocol are found to be excellent.

Phthalocyanines Synthesis: A State-of-The-Art Review of Sustainable Approaches Through Green Chemistry Metrics.

Driven by escalating environmental concerns, synthetic chemistry faces an urgent need for a green revolution. Green chemistry, with its focus on low environmental impacting chemicals and minimized waste production, emerges as a powerful tool in addressing this challenge. Metrics such as the E-factor guide the design of environmentally friendly strategies for chemical processes by quantifying the waste generated in obtaining target products, thus enabling interventions to minimize it. Phthalocyanines (Pcs), versatile molecules with exceptional physical and chemical properties, hold immense potential for technological applications. This review aims to bridge the gap between green chemistry and phthalocyanine synthesis by collecting the main examples of environmentally sustainable syntheses documented in the literature. The calculation of the E-factor of a selection of them provides insights on how crucial it is to evaluate a synthetic process in its entirety. This approach allows for a better evaluation of the actual sustainability of the phthalocyanine synthetic process and indicates possible strategies to improve it.

Insights into the development of greener mild zeolite dealumination routes applied to the hydrocracking of waste plastics

This study highlights novel, energy-efficient, environmentally friendly and less time-consuming methods to dealuminate zeolites, by forced convective steaming and use of molecular CO2. Zeolites with comparable (or superior) physicochemical properties than those of traditional dealumination techniques were produced. All dealuminated zeolites were tested for the hydrocracking of high-density polyethylene, showing considerably high activity and selectivity for lighter oils, particularly gasoline. The forced convective steamed zeolite revealed to be the best, given its high number of silanol groups, acidity and porosity, and lower environmental impact. Furthermore, bi-functional Ni-loaded dealuminated zeolites showed good stability and ability to be regenerated. Therefore, it is possible to generate hierarchical zeolites by dealumination with physicochemical and catalytic properties comparable to their rival technologies, following green chemistry metrics. Given the relevance of hierarchical zeolites in sustainable routes to produce chemicals and fuels, the potential of application of these newly developed catalysts is highly promising and vast.

Continuous, solvent-free, and mechanochemical synthesis of UIO-66 (Mn) by gas-solid two-phase flow and mechanism research

In this work, we introduced a novel gas-solid two-phase flow technique (GSF) for the continuous mechanochemical synthesis of the classic MOFs structure UIO-66(Mn). The synthesized product was thoroughly examined using Fourier transform infrared spectroscopy, powder X-ray diffraction, single crystal X-ray diffraction, differential thermal analysis, thermogravimetric analysis, XPS Method, and transmission electron microscopy. The results indicated that the product, synthesized using this method, was analytically pure and achieved a high yield without any by-products. We also explored its preparation mechanism by introducing the classical model of solid-phase reaction. The green chemistry metrics of this approach suggest it was significantly more environmentally friendly. Moreover, this work demonstrateed that the method can replace traditional solvothermal methods, offering a novel approach for the mechanochemical synthesis of MOFs.

Green voltammetric method for determination of diclofenac sodium in environmental and biological samples using aluminium tungstate nanoparticles modified carbon paste electrode

ABSTRACT Based upon aluminium tungstate (Al2(WO4)3 NPs), a new modified sensor was created in order to monitor diclofenac sodium (DCF) electrochemically in environmental samples. The electrode composition, electrolyte effect, selectivity, scan rate, and pH parameters that affect the assay’s performance were optimised and the pH study revealed that pH 3.6 was found to be suitable to improve the electrochemical behaviour of diclofenac. The electrochemical characteristics of the built-in electrode were assessed using cyclic voltammetry technique (CV).The electrode composition, electrolyte effect, selectivity, scan rate, and pH parameters were optimised. The limit of detection was found to be 0.076 µM and the limit of quantification (LOQ) value was 0.25 µM for the concentration range (0.2–25 µM) of DCF. It has demonstrated good selectivity for (DCF) in presence of the interfering species and its electrochemical sensing’s repeatability, reproducibility and stability were evaluated and found typical. Some environmental samples like tap water, waste water, Nile-river water and biological ones like urine and plasma, have been effectively applied using the proposed electrochemical sensor. Green chemistry metrics, viz. Analytical GREEnness Preparation (AGREEprep), Analytical Eco-Scale Assessments (ESA) and The AMVI for the proposed method were calculated and have assured that the method has limited negative impact on both human health and the environment.

Sustainable Plantwide Optimizing Control for an Acrylic Acid Process.

This paper presents a sustainable control strategy from a plantwide control (PWC) perspective. The proposed strategy is subjected to testing within an operational environment of an acrylic acid plant. To integrate sustainability tools into the plantwide optimizing control (PWOC) formulation, the present proposal suggests the utilization of green chemistry principles. These principles will be incorporated as constraints within the optimization problem. A comparative analysis is conducted between the proposed sustainable PWOC approach and two alternative structures: a PWOC framework that does not take sustainability issues into account and a conventional PWC structure. The findings indicate that the sustainable PWOC demonstrates superior economic performance from a financial standpoint, reaching the highest cumulative profitability(1.6274 × 105 USD), exceeding 11.94% in comparison to the PWOC without sustainability concerns, which reach a cumulative profitability of 1.4330 × 105 USD, and surpassing 13.01% when compared to the decentralized PWC approach, which reach a cumulative profitability of 1.4158 × 105 USD. Additionally, the sustainable PWOC demonstrated a reduced emission impact on the process, with a decrease of 6.17% compared to the unsustainable PWOC and a 9.79% decrease compared to the decentralized approach. This demonstrates that the incorporation of the proposed green chemistry metrics as an explicit component of the formulated PWC problem significantly mitigates the impacts of global warming and human health.

Green HPLC–DAD method for the analysis of analgesic and antihistamine drugs adulterated in herbal mixtures

This study presents a HPLC-DAD method developed for the simultaneous detection of histamine H1 antagonist drugs and analgesic compounds, including paracetamol, cetirizine hydrochloride, cinnarizine, chlorpheniramine maleate, and loratadine, in herbal formulations. This method systematically investigates critical parameters for enhancing separation and quantification using HPLC-DAD. Chemometric techniques were employed to optimize the method for detecting adulterants, with sample preparation involving liquid-phase extraction and a mobile phase for separation using HPLC-DAD. The calibration curves were linear over concentrations ranging from 10 to 40 µg/mL, with correlation coefficients exceeding 0.99. The method exhibits good accuracy, with mean recoveries ranging from 90 to 105 %, and precision (% RSD) for intraday and interday precision: 0.71 to 2.94 %. The limits of detection (LODs) and limits of quantification (LOQs) for each compound are provided. The HPLC-DAD method ensures rigorous quality control, detecting potential adulteration in 32 traditional medicine samples and emphasizing its safety and efficacy in managing allergic conditions. The proposed approach is considered environmentally friendly based on evaluations from commonly used greenness assessment tools, Green analytical chemistry metrics (ComplexGAPI, AGREE, BAGI) confirm the method's sustainability and practicality.

Mimicking Ozonolysis via Mechanochemistry: Internal Alkynes to 1,2-Diketones using H5IO6.

Utilizing periodic acid as an environmentally benign oxidizing agent, this study introduces a novel mechanochemical method that mimics ozonolysis to convert internal alkynes into 1,2-diketones, showcasing effective emulation of ozone's reactivity. Notably, this oxidation occurs at room temperature in aerobic conditions, eliminating the need for toxic transition metals, hazardous oxidants, or expensive solvents. Through control experiments validating the mechanism, substantial evidence supports a concerted reaction pathway. This progress marks a significant stride toward cleaner and more efficient chemical synthesis, mitigating the environmental impact of conventional processes. Assessing the green chemistry metrics in both solvent-free and previously reported solvent-based methods, our eco-friendly protocol demonstrates an E-factor of 7.40, a 51.7 % atom economy, a 45.5 % atom efficiency, 100 % carbon efficiency, and 11.9 % reaction mass efficiency when solvents are not used.

Exploring the potentialities of a biodegradable polymeric film in sample preparation: An optimized “white” protocol to extract and quantify emerging contaminants in water

BackgroundThe introduction of white analytical chemistry encourages the development of methods characterized by a balance among greenness, productivity/feasibility and analytical performances. In the environmental analysis of emerging contaminants (ECs), for which high sensitivity and specificity are mandatory, the use of green and sustainable sample preparation needs to be coupled to a reliable analytical determination. Herein, an extraction method based on the use of a biodegradable polymeric film (Mater-Bi) and coupled to LC-MS/MS analysis was developed for the sensitive determination of ECs in wastewater. ResultsThe interaction among a range of ECs and the Mater-Bi film (a commercially available patented blend of polybutylene-terephthalate, starch and fatty acids) was investigated by two sequential experimental designs, to simultaneously study several factors and optimize extraction efficiency. The final method, resembling a fabric phase sorptive extraction, involved pH and ionic strength modification of the sample, 1h extraction and desorption in ethanol. Satisfactory recoveries from real wastewater were obtained for sixteen analytes (56–116 %), as well as excellent precision (inter-day relative standard deviations below 10 % for most compounds). Matrix effect was in the range 88–116 % at the lower pre-concentration factor, but also acceptable in most cases at the higher pre-concentration factor. LODs in matrix, from 0.004 to 0.159 μg L−1, were lower than or comparable to those from recent studies employing green extraction procedures. The method demonstrated its applicability to samples from wastewater treatment plants, allowing quantification of pharmaceuticals and UV filters at the μg L−1 and ng L−1 levels, respectively. SignificanceFor the first time, the synthetic biopolymer Mater-Bi, so far unexplored for the use in analytical chemistry, was exploited for a green, simple and extremely cheap extraction protocol. The optimized method is suitable for several ECs, guaranteeing very good accuracy, precision and specificity, also thanks to the LC-MS/MS analysis. The evaluation by green and white analytical chemistry metrics highlighted its superiority to conventional extraction methods.

Green conversion of carbon disulfide to degradable polydithiourethanes through catalyst-free multicomponent polymerizations of diamines, carbon disulfide and diacrylates

In the pursuit of advanced functional polymer materials, sulfur-containing polymers have received tremendous attention owing to their superior chemical stability, high refractive indices, various supramolecular interactions, and robust dynamic covalent chemistry. However, their synthesis usually involves either expensive monomers or toxic byproducts and requires catalysts, thus hindering their widespread application. In this work, we present a catalyst-free multicomponent polymerization in organic solvents for the synthesis of various polydithiourethanes with excellent yields (up to 98 %) and high molecular weights (up to 112 kg/mol). This reaction involves the direct polymerization of carbon disulfide, an abundant one-carbon feedstock, with commercially available diamines and diacrylates. This polyaddition process demonstrates high atom economy and no byproduct, occurring at room temperature without the need for a catalyst, thus exhibiting excellent green chemistry metrics. By utilizing the dynamic covalent chemistry of dithiourethane groups, these polymers can be efficiently degraded via aminolysis and used to fabricate reprocessable vitrimers. This multicomponent polymerization opens up a new avenue for the efficient utilization of carbon disulfide resources and accelerates the exploration of diversified sulfur-containing functional polymer materials.

Facile one-pot green synthesis of Aloe vera mediated silver nanoparticles and their catalytic efficiency towards organic transformations

A facile approach for the synthesis of Aloe vera mediated silver nano-particles (AgNPs) has been carried out via chemical route. The developed Aloe vera mediated AgNPs were characterized by using various techniques such as SEM, FT-IR etc. Additionally, catalytic applications of this interesting nanomaterial were utilized for the synthesis of 4-phenylthiazole- 2-amine and its derivatives. After completion of catalytic reactions, Aloe vera mediated AgNPs were easily recycled without any significant loss in catalytic activity. The robust features of the current approach involve an outstanding catalytic performance, ease of catalyst retrievability, easy work up procedure, and large substrate tolerance. Besides this, the green chemistry metrics for the products formed such as E-factor (Environment Factor), PMI (Process Mass Intensity), RME (Reaction Mass Efficiency), Atom Economy (AE) and carbon efficiency (CE) were in associated with high efficiency and selectivity which further confirms the effectiveness of this approach. This work highlights the significance of using economic and eco-friendly approach for synthesizing thiazole derivatives in good to excellent yields via Aloe vera mediated AgNPs under waste free conditions.