Protein click chemistry and its potential for medical applications.

A revolution in chemical biology occurred with the introduction of click chemistry. Click chemistry plays an important role in protein chemistry modifications, providing specific, sensitive, rapid, and easy-to-handle methods. Under physiological conditions, click chemistry often overlaps with bioorthogonal chemistry, defined as reactions that occur rapidly and selectively without interfering with biological processes. Click chemistry is used for the posttranslational modification of proteins based on covalent bond formations. With the contribution of click reactions, selective modification of proteins would be developed, representing an alternative to other technologies in preparing new proteins or enzymes for studying specific protein functions in different biological processes. Click-modified proteins have potential in diverse applications such as imaging, labeling, sensing, drug design, and enzyme technology. Due to the promising role of proteins in disease diagnosis and therapy, this review aims to highlight the growing applications of click strategies in protein chemistry over the last two decades, with a special emphasis on medicinal applications.

Retraction: Aqueous aerobic oxidation of alkyl arenes and alcohols catalyzed by copper(II) phthalocyanine supported on three-dimensional nitrogen-doped graphene at room temperature.

Retraction of 'Aqueous aerobic oxidation of alkyl arenes and alcohols catalyzed by copper(II) phthalocyanine supported on three-dimensional nitrogen-doped graphene at room temperature' by Mojtaba Mahyari et al., Chem. Commun., 2014, 50, 7855-7857, https://doi.org/10.1039/C4CC01406E.

Isocyanide-based multicomponent reactions for the synthesis of benzopyran derivatives with biological scaffolds.

Benzopyrans (BZPs) are among the most privileged and influential small O-heterocycles that form the core of many natural compounds, commercial drugs, biological compositions, agrochemicals, and functional materials. BZPs are divided into six general categories including coumarins, chromans, 2H-chromenes, 4H-chromenes, chromones, and 4-chromanones, each of which is abundant in many plants and foods. These oxygenated heterocyclic compounds are fascinating motifs and have extensive applications in biology and materials science. Hence, numerous efforts have been made to develop innovative approaches for their extraction and synthesis. However, most of them are step-by-step or multi-step strategies that suffer from waste material generation and a tedious extraction process. Isocyanide-based multicomponent reactions (I-MCRs) offer a highly efficient method for overcoming these problems. The I-MCR is a simple and environmentally friendly one-pot domino procedure that does not require intermediate isolation or workup and is generally more efficient in material usage. This review covers all research articles related to I-MCRs for synthesizing BZP derivatives from the beginning to the middle of the year 2023. This strategy will be useful for organic and pharmaceutical chemists to design new drugs and optimize the synthesis steps of biological compounds and commercial drugs with benzopyran cores.

Cyclodextrin Host-Guest Recognition in Glucose-Monitoring Sensors.

Diabetes mellitus is a prevalent chronic health condition that has caused millions of deaths worldwide. Monitoring blood glucose levels is crucial in diabetes management, aiding in clinical decision making and reducing the incidence of hypoglycemic episodes, thereby decreasing morbidity and mortality rates. Despite advancements in glucose monitoring (GM), the development of noninvasive, rapid, accurate, sensitive, selective, and stable systems for continuous monitoring remains a challenge. Addressing these challenges is critical to improving the clinical utility of GM technologies in diabetes management. In this concept, cyclodextrins (CDs) can be instrumental in the development of GM systems due to their high supramolecular recognition capabilities based on the host-guest interaction. The introduction of CDs into GM systems not only impacts the sensitivity, selectivity, and detection limit of the monitoring process but also improves biocompatibility and stability. These findings motivated the current review to provide a comprehensive summary of CD-based blood glucose sensors and their chemistry of glucose detection, efficiency, and accuracy. We categorize CD-based sensors into four groups based on their modification strategies, including CD-modified boronic acid, CD-modified mediators, CD-modified nanoparticles, and CD-modified functionalized polymers. These findings shed light on the potential of CD-based sensors as a promising tool for continuous GM in diabetes mellitus management.

Using Triazolobenzodiazepine as the Cyclic Imine in Various Types of Joullié-Ugi Reactions.

The triazolobenzodiazepine as a cyclic imine was employed in a variety of Joullié-Ugi reactions, and three new families of unique triazolobenzodiazepine connected to carboxamide and tetrazole products were synthesized via a three-component reaction of the cyclic imine and isocyanides with each species of a carboxylic acid/water/TMSN3 under mild conditions in high yields. Furthermore, triazolobenzodiazepine imine was used in an interesting strategy based on the modified Ugi reaction (pseudo-Joullié-Ugi reaction) of cyclic imines with an isocyanide and acetylenedicarboxylates under catalyst-free conditions for the synthesis of triazolobenzodiazepine-fused pyrroles. Mechanistic investigation reveals that triazolobenzodiazepine-fused pyrroles have been generated via a surprising route. Significantly, the use of triazolobenzodiazepine in the Joullié-Ugi, azido-Joullié-Ugi, and pseudo-Joullié-Ugi reactions of a broad scope of biological scaffolds occurred under mild, simple conditions without any catalyst.

The new synthesis of pyrrole-fused dibenzo[b,f][1,4]oxazepine/thiazepines by the pseudo-Joullié-Ugi reaction via an unexpected route with high chemoselectivity.

A novel and unexpected route for synthesizing pyrrole-fused dibenzoxazepines/thiazepines has been designed based on a modified Ugi reaction of cyclic imines with isocyanides and acetylenedicarboxylates under catalyst-free conditions. Mechanism investigation indicates that this process is carried out through the production of zwitterion species (Huisgen's 1,4-dipole), which is a key intermediate in the chemoselectivity of products. This Huisgen's 1,4-dipole is trapped in situ with isocyanides and a variety of pyrrole-fused dibenzoxazepines/thiazepines are synthesized in a simple one-pot operation with high yields and chemoselectivity. This strategy opens a new route in Ugi reactions (pseudo-Joullié-Ugi reaction) for the synthesis of pyrrole-fused heterocycles as special pharmaceutical scaffolds.

Cellulose-based nanocomposite for ultrasonic assisted dispersive solid phase microextraction of triazole fungicides from water, fruits, and vegetables samples.

Herein, an ultrasound-assisted dispersive solid phase microextraction (UA-DSPME) approach has been described for trace level analysis of triazole fungicides in real samples. For this purpose, a new nanosorbent was prepared through modification of carboxymethylcellulose biopolymer with zinc-based metal-organic framework and graphene oxide, and fully characterized. Then, the effect of extraction parameters on extraction efficiency was optimized for the microextraction process. Finally, desorbed triazole fungicides with ethanol were determined using gas chromatography equipped with flame ionization detector. This technique provided good linearity (R2 > 0.99), low detection limits (0.3-1.5 ng mL-1), high preconcentration factors (419-426), good relative recoveries (91.6-102 %), and high repeatability (RSD < 4.1 %) at optimized conditions (amount of sorbent: 15 mg; pH of solution: 7.0; and extraction time; 4 min). Ultimately, this approach was applied to determine triazole fungicides in different water and food samples.

Isocyanide-Based Multicomponent Reactions in Water: Advanced Green Tools for the Synthesis of Heterocyclic Compounds.

Reaction rate acceleration using green methods is an intriguing area of research for chemists. In this regard, water as a "green solvent" plays a crucial role in the acceleration of some organic transformations and reveals exclusive selectivity and reactivity in comparison with conventional organic solvents. In particular, multicomponent reactions (MCRs) as sustainable tools lead to the rapid generation of small-molecule libraries in water and aqueous media due to the prominent role of the hydrophobic effect. MCRs, as diversity-oriented synthesis (DOS) methods, have great efficiency with simple operations, atom, pot, and step economy synthesis, and mechanistic beauty. Among diverse classes of MCRs, isocyanide-based multicomponent reactions (I-MCRs), as sustainable and versatile reactions, have gained considerable attention in the synthesis of diverse heterocycle rings, especially in drug design because of the peculiar nature of isocyanide as a particular active reactant. I-MCRs that are performed in water are mild, environmentally friendly, and easily controlled, and have a reduced number of workup, purification, and extraction steps, which fit well with the advantages of "green" chemistry. Performing these powerful organic transformations in water and aqueous media is accompanied by acceleration owing to negative activation volumes, which originate from connecting several reactants together to generate a single product. It should be noted that the combination of MCR strategy and aqueous phase reaction is of growing interest for the development of sustainable synthetic techniques in organic conversions. However, an exclusive account focusing on the recent progress in eco-friendly I-MCRs for the construction of heterocycles in water and aqueous media is particularly lacking. This review highlights the progress of various kinds of I-MCRs in water and aqueous media as benign methods for the efficient construction of vital heterocyclic scaffolds, with a critical discussion of the subject in the period 2000-2021. We hope that this themed collection will be of interest and beneficial for organic and pharmaceutical chemists and will inspire more reaction development in this fascinating field.

Correction: Gold nanoparticles supported on supramolecular ionic liquid grafted graphene: a bifunctional catalyst for the selective aerobic oxidation of alcohols.

[This corrects the article DOI: 10.1039/C3RA44696D.].

Copper phthalocyanine-conjugated pectin via the Ugi four-component reaction: An efficient catalyst for CO2 fixation.

Due to the cost-effectivity and biodegradability advantages of pectin, this type of polysaccharide attracted the attention of many researchers for catalyst construction. Accordingly, pectin was used as a green support in this study to construct an efficient heterogeneous catalytic system based on the conjugation of metal phthalocyanines. To end this, pectin was first oxidized with periodate oxidant agent to effectively immobilize a tetra-amino copper phthalocyanine (Cu-PcTA) through a green, simple, and an efficient one-pot Ugi four-component reaction (Ugi-4CR). Then, the catalytic activity of the copper phthalocyanine-conjugated pectin was investigated in the CO2 fixation reaction to cyclic carbonates. Optimum catalytic conditions were as follows: 30 mg of prepared catalyst, 3 bar CO2 pressure, 90 °C, 2 h, and TBAB as a co-catalyst. Pectin can successfully improve the catalytical properties of the Cu-PcTA over the CO2 fixation reaction.

Application or function of citric acid in drug delivery platforms.

Nontoxic materials with natural origin are promising materials in the designing and preparation of the new drug delivery systems (DDSs). Today's, citric acid (CA) has attracted a great deal of attention because of its special features; green nature, biocompatibility, low price, biodegradability, and commercially available property. So, CA has been employed in the preparation of the various platforms to induce a suitable property on their structure. Recently, several research groups investigated the CA-based platforms in different forms like tablets, dendrimers, hyperbranched polymers, (co)polymer, hydrogels, and nanoparticles as efficient DDSs. By considering an increasing amount of published articles in this field, for the first time, in this review, an overview of the published works regarding CA applications in the design of various DDSs is presented with a detailed and insightful discussion.

Carboxymethyl cellulose/tetracycline@UiO-66 nanocomposite hydrogel films as a potential antibacterial wound dressing.

Designing an antibacterial agent with a suitable water vapor permeability, good mechanical properties, and controlled antibiotic release is a promising method for stopping bacterial infection in wound tissue. In this respect, this work aims to prepare novel flexible polymeric hydrogel films via integrating UiO-66 into the polymeric carboxymethyl cellulose (CMC) hydrogel for improving the mechanical and antibiotic release performances. First, we performed a green hydrothermal synthetic method to synthesis UiO-66 and followed by encapsulating Tetracycline (TC) through immersion in its aqueous solution. Also, the casting technique was utilized to integrate different concentrations of the TC-encapsulated UiO-66 (TC@UiO-66, 5% to 15%) in the polymeric CMC matrix (CMC/TC@UiO-66) cross-linked by citric acid and plasticized by glycerol. The release performance showed a low initial burst release with a controlled release over 72 h in the artificial sweat and simulated wound exudate (PBS, pH 7.4) media. The in vitro cytotoxicity and antibacterial activity results revealed a good cytocompatibility toward Human skin fibroblast (HFF-1) cells and a significant activity against both E. coli and S. aureus with 1.3 and 1.7 cm inhibition zone, respectively. The obtained results recommend CMC/TC@UiO-66 films as a potential antibacterial wound dressing.

Cu-decorated cellulose through a three-component Betti reaction: An efficient catalytic system for the synthesis of 1,3,4-oxadiazoles via imine CH functionalization of N-acylhydrazones.

Materials functionalization through multicomponent reactions (MCRs) has recently attracted great attention due to the generation of outstanding features in materials. Herein, an efficient novel heterogeneous catalytic system was designed and synthesized via the MCRs functionalization of the most abundant biopolymer in nature, cellulose. In this regard, cellulose was oxidized using periodate as an oxidant agent, and then the resulted carbonyl functional groups participated in the three-component Betti reaction. The ICP-OES analysis was revealed that the functionalization of cellulose via this three-component reaction effectively improved the complexing ability of functionalized cellulose with Cu(II). The synthesized biocatalyst was characterized by FT-IR, 1H NMR, XRD, SEM, EDS, ICP, and TGA techniques. The efficiency of the designed biocatalyst was investigated in the CH functionalization reaction of N-acylhydrazones to synthesize 1,3,4-oxadiazoles. This biocatalyst's outstanding advantages are high yields, non-hazardous catalyst, mild reaction conditions, operational simplicity, and reusability.

Nanoscale Metal-Organic Frameworks: Recent developments in synthesis, modifications and bioimaging applications.

Porous Metal-Organic Frameworks (MOFs) have emerged as eye-catching materials in recent years. They are widely used in numerous fields of chemistry thanks to their desirable properties. MOFs have a key role in the development of bioimaging platforms that are hopefully expected to effectually pave the way for accurate and selective detection and diagnosis of abnormalities. Recently, many types of MOFs have been employed for detection of RNA, DNA, enzyme activity and small-biomolecules, as well as for magnetic resonance imaging (MRI) and computed tomography (CT), which are valuable methods for clinical analysis. The optimal performance of the MOF in the bio-imaging field depends on the core structure, synthesis method and modifications processes. In this review, we have attempted to present crucial parameters for designing and achieving an efficient MOF as bioimaging platforms, and provide a roadmap for researchers in this field. Moreover, the influence of modifications/fractionalizations on MOFs performance has been thoroughly discussed and challenging problems have been extensively addressed. Consideration is mainly focused on the principal concepts and applications that have been achieved to modify and synthesize advanced MOFs for future applications.

Chemoselective synthesis of fully substituted pyrroles via a one-pot four-component isocyanide-based reaction.

Small-ring heterocycles comprising pyrrole and pyrazole are well known for their rich biological properties. In this article, an efficient green sonochemical approach was designed for the synthesis of novel, fully substituted pyrroles connected to pyrazole scaffolds via a one-pot, four-component isocyanide-based sequential reaction. This reaction was carried out using various 5-amino-pyrazoles, aldehydes, dialkyl acetylenedicarboxylates and isocyanides for the synthesis of fully functionalized pyrroles with high chemoselectivity in the presence of a catalytic amount of PTSA·H2O, in good to excellent yields under ultrasound irradiation. This waste-free (-H2O) reaction exhibited a high atom economy and step economy via creating four new bonds, including two C-N and two C-C bonds, and the formation of two five-member heterocycles which are connected in a single operation. The mechanism of this four-component domino process involved sequential imination-dipolar cyclization-[1,5]-H shift reactions. The synthesized compounds possess interesting fluorescence features, and the bioactive scaffolds might attract great interest in the fields of clinical diagnostics and biomedical research in the future.

Ultrasound-assisted synthesis of MIL-88(Fe) coordinated to carboxymethyl cellulose fibers: A safe carrier for highly sustained release of tetracycline.

For stopping long-time harmful bacterial infection, designing a drug carrier with a highly prolonged release profile is a promising approach that is of interest to different biomedical areas. The subject of this work is to synthesis a novel carrier system through coordination of MIL-88(Fe) to carboxymethyl cellulose (CMC) for enhancing interaction between drug and carrier. We established an ultrasound-assisted synthetic method for in situ synthesis of MIL-88(Fe) in the presence of CMC resulting in CMC/MIL-88(Fe) composite. The CMC/MIL-88(Fe) was loaded with a high amount of Tetracycline (TC) by immersion of carrier to the TC aqueous solution. The release profile in the simulated physiological conditions, pH 7.4, revealed a low initial burst release followed by a sustained and prolonged release over 384 h. The in vitro cytotoxicity of CMC/MIL-88(Fe) against Human skin fibroblast (HFF-1) cells was calculated by MTT assay and showed a good cytocompatibility. The antibacterial activity was found for TC-loaded CMC/MIL-88(Fe) toward both E. coli and S. aureus with MIC 64 mg·ml-1.

Multicomponent reactions as a potent tool for the synthesis of benzodiazepines.

Benzodiazepines (BZDs), a diverse class of benzofused seven-membered N-heterocycles, display essential pharmacological properties and play vital roles in some biochemical processes. They have mainly been prescribed as potential therapeutic agents, which interestingly represent various biological activities such as anticancer, anxiolytic, antipsychotic, anticonvulsant, antituberculosis, muscle relaxant, and antimicrobial activities. The extensive biological activities of BZDs in various fields have encouraged medicinal chemists to discover and design novel BZD-based scaffolds as potential therapeutic candidates with the favorite biological activity through an efficient protocol. Although certainly valuable and important, conventional synthetic routes to these bicyclic benzene compounds contain methodologies often requiring multistep procedures, which suffer from waste materials generation and lack of sustainability. By contrast, multicomponent reactions (MCRs) have recently advanced as a green synthetic strategy for synthesizing BZDs with the desired scope. In this regard, MCRs, especially Ugi and Ugi-type reactions, efficiently and conveniently supply various complex synthons, which can easily be converted to the BZDs via suitable post-transformations. Also, MCRs, especially Mannich-type reactions, provide speedy and economic approaches for the one-pot and one-step synthesis of BZDs. As a result, various functionalized-BZDs have been achieved by developing mild, efficient, and high-yielding MCR protocols. This review covers all aspects of the synthesis of BZDs with a particular focus on the MCRs as well as the mechanism chemistry of synthetic protocols. The present manuscript opens a new avenue for organic, medicinal, and industrial chemists to design safe, environmentally benign, and economical methods for the synthesis of new and known BZDs.

Gelatin microsphere coated Fe3O4@graphene quantum dots nanoparticles as a novel magnetic sorbent for ultrasound-assisted dispersive magnetic solid-phase extraction of tricyclic antidepressants in biological samples.

Gelatin microsphere-coated Fe3O4@graphene quantum dots (Fe3O4@GQD@GM) were designed and synthesized as a novel sorbent via ultrasonic-assisted dispersive magnetic solid-phase extraction (UA-DMSPE) method. The synthesized sorbent was identified and confirmed by FT-IR, XRD, VSM, and SEM techniques. UA-DMSPE was combined with corona discharge ion mobility spectrometry for trace determination of desipramine, sertraline, and citalopram. Effective parameters were considered and optimized. The proposed method, under optimal conditions, showed excellent linearity in different concentration ranges (2-700 ng mL-1, R2 > 0.995), repeatability (RSD < 5.1%), good sensitivity (LODs in the range 0.6-1.5 ng mL-1), high preconcentration factor (PF = 207-218), and acceptable relative recoveries (93.5-101.8%). Eventually, this method was used to determine tricyclic antidepressants in various biological samples. Schematic presentation of the microextraction and monitoring of TCAs by ultrasonic-assisted dispersive magnetic solid phase microextraction-ion mobility spectrometry producer.