A hyperporous polymer-based quartz crystal microbalance (QCM) chemosensor was developed for the selective determination of the signature peptide ELPLYR, a clinically significant biomarker for the prognosis of small-cell lung cancer. The sensor consists of an ELPLYR-imprinted poly(3,4-ethylenedioxythiophene) (PEDOT) recognition film electrosynthesized on gold-sputtered quartz (Au/quartz) transducers. Synthetic receptor-like cavities for ELPLYR were embedded within the PEDOT matrix using molecular imprinting. Hierarchical hyperporous networks of imprinted (MIP) and reference (REF) polymer films were fabricated using self-assembled, crystal-lattice-like sacrificial templates of amine-modified latex beads (LB-NH2). Imprinting of ELPLYR was achieved via electropolymerization of 3,4-ethylenedioxythiophene (EDOT) and functionalized monomers (EDOT-OH and EDOT-NH2) on the ELPLYR-modified, LB-NH2-coated Au/quartz surface. 1H NMR spectroscopy, molecular dynamics, and docking simulations confirmed strong hydrogen-bonding interactions between ELPLYR and the functional monomers in the prepolymerization solution. Selective extraction of the LB-NH2 beads and the ELPLYR template yielded a hyperporous network with surface-confined imprinted cavities. Microscopic (SEM and profilometry), electrochemical (CV and EIS), and spectroscopic (XPS and RAIRS) characterization revealed a uniformly grown, permeable, and long-range ordered PEDOT film (approx. 0.3 mu m thick) with interconnected cavities maintained over millimeter scales. QCM measurements under flow injection analysis (FIA) conditions demonstrated the highly selective binding of ELPLYR to the hyperporous structure (MIP-Np-S + B). The sensitivity was found to be 166.51 +/- 22.35 Hz/mM (R² = 0.998), which is more than 5-fold higher than that of the nonimprinted analogue (REF-Np, 33.06 +/- 1.47 Hz/mM, R² = 0.997). The sensor exhibited excellent cross-reactivity, selectively detecting ELPLYR over structural interferents such as Z-ELPLYR (73.30 +/- 3.91 Hz/mM) and a constituent amino acid cocktail (11.37 +/- 2.23 Hz/mM). Furthermore, the sensor successfully recognized ELPLYR in artificial cerebrospinal fluid. Under optimized FIA conditions, the linear dynamic range extended from 39 ng/mL to 450 mu g/mL (R² = 0.998), with a limit of quantitation of 78 ng/mL (S/N = 5). Finally, the platform detected the signature peptide in blood and digested serum samples (100 ng/mL) collected via quantitative dried blood spot cards, demonstrating its potential for on-site sampling and clinical diagnostics. This work highlights the critical role of hierarchical nanostructures in enhancing chemosensor performance and the feasibility of peptide detection in complex biological fluids.

Electrochemical deuteration is emerging as a powerful and sustainable strategy for introducing deuterium into organic molecules, providing a green alternative to traditional isotope-labeling methods. Over the past two years, significant advances have been made in both metal-catalyzed and metal-free electrochemical systems that enable site-selective deuteration under mild conditions. These developments have expanded the substrate scope, new synthetic methods development, improved reaction efficiency, and reduced the need for steps and hazardous reagents. Furthermore, mechanistic insights derived from electroanalytical techniques have deepened our understanding of electron transfer processes in deuterium incorporation. This review highlights key breakthroughs reported since 2022, discusses underlying mechanistic principles, and outlines emerging trends in reaction design and scalability. Collectively, these innovations underscore the growing importance of electrochemical methods in achieving sustainable isotopic labeling for pharmaceutical chemistry applications.

A metal-free electrochemical desulfurization of thioamides is reported, enabled by an isobutyric acid-mediated Kolbe radical initiation under air. The protocol operates in an undivided cell, tolerates diverse substrates, and proceeds via radical activation and oxygen trapping, offering a mechanistically distinct, sustainable alternative to conventional oxidative desulfurization methods.

The past two decades have witnessed the introduction of and then a steady increase in the use of computational techniques in the study and development of molecularly imprinted polymers (MIPs). Molecular dynamics (MD) based studies have had a significant role in this development as they can provide insights concerning the mechanisms governing the molecular level events underlying MIP synthesis and MIP-ligand interactions and can be used for the identification of preferred monomer compositions and for the prediction of MIP properties. We here review the role that MD has played in the development of molecular imprinting and examine the different types of MD strategies that have been used, including their advantages and challenges. Recent trends in the application of MD to the study of MIPs are presented, along with a perspective on the future importance of MDbased studies for the development of molecular imprinting science and technology.

Theoretical treatments have been widely used over recent years for the investigation and development of molecularly imprinted materials, in particular for improving our understanding of the molecular mechanisms underlying the nature of the recognition events involved in the synthesis of MIPs and of MIP–ligand interactions. This chapter aims to present the different types of theory-based calculations—from quantum mechanical (QM) to semiempirical methods, followed by classical molecular dynamics (MD). The first section introduces the advantages and disadvantages imposed by each method, the second focuses on QM and MD techniques, alongside hybrid approaches for template optimization, while the third part outlines the optimization/investigation methods used for functional monomer selection. The T-FM interactions with cross-linking and porogenic agents are also considered. The final part of the chapter is focused on additional computational approaches for studying MIP systems, including binding energy calculations, structural and dynamical measurements, multivariate descriptors, and chemometric models. Finally, general conclusions and future prospects for the use of theoretical methods in the study and development of MIPs are presented.

Cancer cells can adapt to their surrounding microenvironment by upregulating glucose-regulated protein 78 kDa (GRP78) and vacuolar-type ATPase (V-ATPase) proteins to increase their proliferation and resilience to anticancer therapy. Therefore, targeting these proteins can obstruct cancer progression. A comprehensive computational study was conducted to investigate the inhibitory potential of four proton pump inhibitors (PPIs), dexlasnoprazole (DEX), esomeprazole (ESO), pantoprazole (PAN), and rabeprazole (RAB), against GRP78 and V-ATPase. Molecular docking revealed high-affinity scores for PPIs against both proteins. Moreover, molecular dynamics showed favorable root mean square deviation values for GRP78 and V-ATPase complexes, whereas root mean square fluctuations were high at the substrate-binding subdomains of GRP78 complexes and the alpha-helices of V-ATPase. Meanwhile, the radius of gyration and the surface-accessible surface area of the complexes were not significantly affected by ligand binding. Trajectory projections of the first two principal components showed similar motions of GRP78 structures and the fluctuating nature of V-ATPase structures, while the free-energy landscape revealed the thermodynamically favored GRP78-RAB and V-ATPase-DEX conformations. Furthermore, the binding free energy was -16.59 and -18.97 kcal/mol for GRP78-RAB and V-ATPase-DEX, respectively, indicating their stability. According to our findings, RAB and DEX are promising candidates for GRP78 and V-ATPase inhibition experiments, respectively.

A novel iridium/silver-based method for catalyzing C-H deuterium labeling of indoles and carbazoles using D2O is presented. The method leverages a carbonyl-based directing group to achieve isotopic incorporation. This method demonstrates broad substrate scope and excellent functional group tolerance, enabling diverse and precise labeling of biologically important heterocycles. Notably, the developed protocol is successfully applied to the late-stage functionalization of carvedilol, showcasing its potential for modifying complex molecules. The operational simplicity, mild conditions, commercially available [Cp*IrCl2]2 as catalyst, D2O as the easily available cheap deuterium source, and high isotopic enrichment make this approach a valuable tool for the synthesis of deuterium-labeled compounds in pharmaceutical and mechanistic studies.

Nickel-catalyzed electrochemical cross-coupling has emerged as an important advancement in synthetic chemistry, combining the versatile catalytic properties of nickel with the sustainability and precision of electrochemical methods. This review captures the recent progress in this dynamic field, focusing on developments published from 2015 onward, and emphasizes the development of innovative catalytic systems and reaction conditions that enhance efficiency, selectivity, and environmental sustainability. Key advancements include novel nickel catalysts, expanded substrate scopes, and mechanistic insights that elucidate the synergistic benefits of electrochemical approaches. By exploring these recent developments, we highlight the transformative potential of nickel-catalyzed electrochemical cross-coupling in facilitating complex bond formation under mild conditions. This comprehensive overview provides a foundation for understanding the current state and future directions of this promising area, emphasizing its significance in advancing green and efficient synthetic methodologies.

The demand for sustainable and environmentally friendly chemical processes has led to the development of innovative catalytic systems and solvent designs. Herein, we report a novel approach utilizing ruthenium catalysis in deep eutectic solvents (DESs) for the selective alkynylation of C-H bonds. Ruthenium, known for its low toxicity and cost-effectiveness, serves as an excellent alternative to other transition metals in eutectic liquids. Moreover, the utilization of supramolecular beta-cyclodextrin-based deep eutectic liquids enhances the eco-friendliness and recoverability of the solvent system. The late-stage functionalization of drugs exemplifies the practical applicability and versatility of this method in organic synthesis, offering a sustainable pathway towards the synthesis of valuable compounds.

A series of nanostructured polysulfobetaine (PSB) hydrogel-coated surfaces were fabricated and tested for hemocompatibility in contact with human blood. PSB films were grafted onto SiO2-coated silicon wafers or Au/quartz via photochemically induced polymerization of a sulfobetaine-based monomer (SBMA, [2-(methacryloylamino)propyl]dimethyl(3-sulfopropyl)ammonium hydroxide). An anodized aluminum oxide (AAO) membrane and latex beads (LB) were used as sacrificial template structures to synthesize polysulfobetaine nanowires (PSBAAO) and hyperporous (PSBLB) networks, respectively. Two soft sacrificial templates, a liquid crystalline medium (LC) and amide-based non-ionic deep eutectic solvent (ni-DESs) providing one-dimensional ordered arrays and flickering clusters, respectively, were utilized to grow nanofibrous (PSBLC) and mesoporous (PSBDES) polysulfobetaine film. Selective dissolution of the sacrificial templates affords the transposed pattern of the template with long-range periodicity from nano to micro scale (20 to 400 nm). Electron micrograph studies revealed nanostructured materials in the form of wires (198 +/- 5 nm), cavities (300 nm) and fibers (20 +/- 2 nm) when AAO, LB and LC-medium were used as templates, while the polymer films prepared from ni-DESs (PSBDES), water (PSBWAT) and methanol (PSBMeOH) were devoid of any noticeable topographical features. PSB-coated surfaces (except for PSBLB) inhibited non-specific adhesion of protein and biomolecules when presented with purified human proteins, i.e., albumin, fibrinogen, hemoglobin, or human plasma, down to 20-125 ng cm(-2) as shown by the QCM studies. Interestingly, the hierarchical nanostructures in polymer films (PSBAAO and PSBLC) resisted the adsorption of albumin and hemoglobin (_20 ng cm(-2)), even at 50 mg mL(-1) concentration. The hemocompatibility of the PSB nanostructures, analyzed after contact with human whole blood for one hour on the PSBAAO and PSBLC, revealed reduced complement activation, quantified as the generation of C3bc fragments and terminal complement sC5b-9 complex formation, in comparison to acrylate glass. The nanowires of PSBAAO showed significantly lower MPO release than the PSBWAT-onto surface, whereas no difference in platelet activation was seen between the surfaces. Compactly organized nanowires and fibers increase the water of hydration layers to strengthen the antifouling and hemocompatibility features, demonstrating the bio-inert nature of the PSB nanostructures. The inherent gelation (hydrophilicity) afforded by the PSB has substantial implications in designing bio-inert surfaces for hemocompatible devices.