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2,4‐Thiazolidinedione (TZD) is a privileged and highly utilised scaffold for the development of pharmaceutically active compounds. This sulfur‐containing heterocycle is a versatile pharmacophore that confers a diverse range of pharmacological activities. TZD has been shown to exhibit biological action towards a vast range of targets interesting to medicinal chemists. In this review, we attempt to provide insight into both the historical conventional and the use of novel methodologies to synthesise the TZD core framework. Further to this, synthetic procedures utilised to substitute the TZD molecule at the activated methylene C5 and N3 position are reviewed. Finally, research into developing clinical agents, which act as modulators of peroxisome proliferator‐activated receptors gamma (PPARγ), protein tyrosine phosphatase 1B (PTP1B) and aldose reductase 2 (ALR2), are discussed. These are the three most targeted receptors for the treatment of diabetes mellitus (DM)., A key scaffold: 2,4‐Thiazolidinedione is a widely recognised structural motif present in many therapeutic agents used for the treatment of diabetes mellitus. This review summarises some of the methods used to prepare biologically active members of this class and discusses the pharmacological potency of these compounds.

Aim: To identify virtual bioisosteric replacements of two GPR40 agonists. Materials & methods: Bioinformatic docking of candidate molecules featuring a wide range of carboxylic acid bioisosteres into complex with GPR40 was performed using TAK-875 and GW9508 templates. Results: This study suggests that 2,6-difluorophenol and squaric acid motifs are the preferred bioisosteric groups for conferring GPR40 affinity. Conclusion: This study suggests that compounds 10 and 20 are worthy synthetic targets.

Graphical abstract, With the emergence of the third infectious and virulent coronavirus within the past two decades, it has become increasingly important to understand how the virus causes infection. This will inform therapeutic strategies that target vulnerabilities in the vital processes through which the virus enters cells. This review identifies enzymes responsible for SARS-CoV-2 viral entry into cells (ACE2, Furin, TMPRSS2) and discuss compounds proposed to inhibit viral entry with the end goal of treating COVID-19 infection. We argue that TMPRSS2 inhibitors show the most promise in potentially treating COVID-19, in addition to being a pre-existing medication with fewer predicted side-effects.

This review intends to act as an overview of fructose malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, irritable bowel syndrome (IBS) and infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients’ experiences either constipation (IBS-C) or diarrhoea (IBS-D). FM has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM’s relationship with small intestinal bacterial overgrowth. It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, monosaccharides and polyols diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurately diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.

Aim: Thiazolidinones were prepared as building blocks for the replacement of carboxylic acids. Materials & methods: Chemical syntheses of thiazolidinones were developed. In addition, the drug-likeness of the target compounds was evaluated in silico. Results: The prepared compounds included the novel structure 4; 5-(3-Iodophenylmethylene)-2,4-thiazolidinedione. Conclusion: Exploration of the methods required to synthesize thiazolidinone building blocks was completed. This work allows future generation of bioisosteric analogs of drugs.

Molecularly imprinted polymers (MIPs) are a type of artificial polymer, which have complementary cavities that are designed to bind a specific target molecule with a high degree of selectivity. Due to their effectiveness and stability, MIPs have found their way into many applications in medicine, chemistry, analysis and sensing fields. One of the most important modern uses of MIPs is the recognition of biological molecules of medical significance, which are called “biomarkers”. The use of MIPs enables easy and rapid extraction and detection of these biomarkers from different biological matrices. There are multiple techniques that arose for synthesis of MIPs each with their own set of advantages and drawbacks. In this review, we discuss MIPs in detail including their different types, methods of synthesis, characterisation methods, common challenges, in addition to their applications in different fields with a focus on their use in the analysis of protein biomarkers.

A rationally designed fluorophore has been developed and has been incorporated into molecularly imprinted polymers, as the basis of the design of a sensor. Its use has allowed the fabrication of two different designs of fibre-optic chemical probes using an approach based on the change of the emitted fluorescence being related to the concentration of the desired species that was present. A high sensitivity to the drug Cocaine was achieved with each of the probes, showing positive changes in the fluorescence signal achieved in response to 1–100 μ M solutions of the drug, in solution in aqueous cetonitrile. High sensitivity for Cocaine over a range of compounds was demonstrated for one of the probes (probe X) and detection of the drug is possible even in the presence of strong fluorescence interference. The work has also shown that probes of this type do not need to be discarded when used: re-use of probe X is possible using a straightforward washing procedure and the calibration performance was maintained.

In this report, a silver@graphene oxide (Ag@GO) nanocomposite-based optical sensor was developed for the detection of biomolecules such as dopamine (DA), ascorbic acid (AA), and uric acid (UA). An aqueous solution of Ag@GO was prepared using a simple chemical reduction method, and it showed a characteristic surface plasmon resonance (SPR) band at 402 nm. The SPR features of the Ag@GO nanocomposite were used for the detection of DA, AA, and UA. The SPR intensity-based limits of detection (LODs) of DA, AA, and UA were 49 nM, 634 nM, and 927 nM, respectively. The SPR band position-based LODs of DA, AA, and UA were 30 nM, 1.64 μM, and 2.15 μM, respectively. The present optical sensor was more sensitive to DA than to UA and AA. The interactions of the biomolecules with Ag@GO were studied based on density functional theory (DFT), and it was found that DA had more interaction than AA and UA. This novel Ag@GO nanocomposite is simple to prepare and showed excellent stability and sensitivity toward the detection of biomolecules.

The detection of cadmium in the environment is very important and in this work the development of an optical fiber chemical sensor for the detection of Cd2+ is described. To achieve this, an optical fiber-based technique has been developed using a sensing layer containing a coumarin fluorophore and dipicolylamine receptor. This was covalently attached to the distal end of an optical fiber and exhibited a significant increase in fluorescence intensity in response to Cd2+ in the μM concentration range via a photoinduced electron transfer (PET) mechanism. Selectivity for Cd2+ over other metal ions has also been demonstrated showing the value of the approach for environmental measurements.

This work aims to develop a stable, compact and portable fibre optic sensing system which is capable of real time detection of the mercury ion (II), Hg2+. A novel fluorescent polymeric material for Hg2+ detection, based on a coumarin derivative (acting as the fluorophore) and an azathia crown ether moiety (acting as the mercury ion receptor), has been designed and synthesized. The material was covalently attached to the distal end of an optical fibre and exhibited a significant increase in fluorescence intensity in response to Hg2+ in the μM concentration range via a photoinduced electron transfer (PET) mechanism. The sensor has also demonstrated a high selectivity for Hg2+ over other metal ions. A washing protocol was identified for sensor regeneration, allowing the probe to be re-used. The approach developed in this work can also be used for the preparation of sensors for other heavy metals.

An optrode able to detect glucose dissolved in water has been implemented. The device is based on the luminescence emission of a Molecularly Imprinted Polymer synthesized specifically for glucose detection, therefore its intensity changes in presence of glucose. This sensing material is attached onto a cleaved ended polymer-clad optical fibre and it is excited by light via 1x2 fibre coupler. The reflected fluorescence signal increases when it is immersed into glucose solutions and recovers to the baseline when it is dipped in ultrapure water. This reversible behaviour indicates the measurement repeatability of using such a glucose sensor.

An intensity ratio technique has been used for characterizing fluorescence spectra from novel coumarin dyes for pH sensing, in the range of 0.5 – 6, providing results that are independent of possible fluctuations in the intensity of the excitation source, deterioration of the indicator and changes in optical coupling. The arrangement was determined to have a sensitivity of 25% per unit pH change (at a pH of 4).

A proof-of-concept mercury probe was developed based on covalent attachment of a chemical coating to optical fibre. The sensing element comprised a dansyl derivative and crown ether moiety, acting as fluorophore and metal ion chelator respectively. An ON-OFF type fluorescence (quench) occurred upon binding of mercury ions, via an intramolecular charge transfer mechanism, in aqueous solution in the 909nM-90.9μM (247 ppb -24.7 ppm) concentration range. A washing protocol was identified for sensor regeneration allowing the probe to be re-used.

This paper is to review the research activities at City University London in the development of a suite of optical fibre-based chemical sensors, including pH, humidity and heavy metal sensors, for environmental monitoring.

Previously, we have developed chemical sensors using fibre optic-based techniques for the detection of Cocaine, utilising molecularly imprinted polymers (MIPs) containing fluorescein moieties as the signalling groups. Here, we report the computational design of a fluorophore which was incorporated into a MIP for the generation of a novel sensor that offers improved sensitivity for Cocaine with a detection range of 1-100 micro-grams. High selectivity for Cocaine over a suite of known Cocaine interferants (25 micro-grams) was also demonstrated by measuring changes in the intensity of fluorescence signals received from the sensor.

Novel chemical sensors using fibre optic-based techniques for the detection of Cocaine have been developed, utilising molecularly imprinted polymers (MIPs) containing fluorescein moieties as the signalling groups. The fluorescent MIPs were formed and covalently attached to the distal end of specially chosen optical fibres to create fibre optic probe-based sensors. These sensors exhibited are producible and quantifiable change in the intensity of the fluorescence signal received from the sensor in response to Cocaine in aqueous acetonitrile mixtures. High selectivity for Cocaine over Codeine and a range of known Cocaine interferants has been demonstrated for one of the sensors developed in this work.

A chemical sensor for the detection of cocaine has been developed, based on a molecularly imprinted polymer (MIP) containing a fluorescein moiety as the signalling group. The fluorescent MIP was formed and covalently attached to the distal end of an optical fibre. The sensor exhibited an increase in fluorescence intensity in response to cocaine in an aqueous acetonitrile mixture. Selectivity for cocaine over codeine has been demonstrated.

The stereoselective, boron-mediated, aldol/reduction sequence, 4+5→8→9, allows an efficient asymmetric synthesis of the δ-lactone-containina. C1–C8 subunit 2 of discodermolide 1.