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.

Electrochemical molecularly imprinted polymers (e-MIPs) were grafted for the first time as a thin layer to the surface of a gold electrode to perform trace level electroanalysis of benzo(a)pyrene (BaP). This was achieved by controlled/living radical photopolymerization of a redox tracer monomer (ferrocenylmethyl methacrylate, FcMMA) with ethylene glycol dimethacrylate in the presence of benzo(a)pyrene as the template molecule. For that purpose, a novel photoiniferter-derived SAM was first deposited on the gold surface. The SAM formation was monitored by cyclic voltammetry and electrochemical impedance spectroscopy. Then, the "grafting from" of the e-MIP was achieved upon photoirradiation during a controlled time. Differential pulse voltammetry was used to quantify BaP in aqueous solution by following the modification of the signal of FcMMA. A limit of detection of 0.19 nM in water and a linear range of 0.66 nM to 4.30 nM, were determined, thus validating the enhancement of sensitivity induced by the close contact between the e-MIP and the electrode, and the improved transfer electron.

Controlled on-surface synthesis of polymer films using amide-based, environmentally friendly, nonionic deep eutectic solvents (ni-DESs) has been developed to regulate the porous features of the films. An appropriate combination of acetamide (A), urea (U), and their methyl derivatives (N-methylacetamide (NMA) and N-methylurea (NMU)) was used to prepare ni-DES. Polymer films were electrosynthesized using 4-aminobenzoic acid (4-ABA) and pyrrole as monomers in ni-DESs. We presumed that the flickering-cluster-like complexes and the extended H-bond networks in ni-DESs enhance the porosity of the polymer films, thus improving permeability features, as reflected in sensor performance. Electrosynthesized polymer films, imprinted with biotin templates (MIPs), have been tested as receptors for biotinylated targets. Molecular dynamics simulations of the prepolymerization mixture revealed the formed complexes between 4-ABA and biotin comprising high-frequency H-bonds. X-ray photoelectron spectroscopy (XPS) and reflection absorption infrared spectroscopy (RAIRS) studies revealed the structural integrity in the polymer films irrespective of the medium. Scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) measurements showed a highly corrugated and porous nature for MIPA-U and MIPNMU-U when prepared in A-U and NMU-U ni-DESs. Atomic force microscope (AFM) studies support these observations, displaying an enhancement in the surface roughness from 1.44 nm (MIPaqueous) to 23.6 nm (MIPNMU-U). QCM analysis demonstrated a remarkable improvement in sensitivity of MIPA-U (17.99 +/- 0.72 Hz/mM) and MIPNMU-U (18.40 +/- 0.81 Hz/mM) films toward the biotin methyl ester (BtOMe, biotin derivative) than the MIPaqueous film. The chemosensor devised with the above MIP recognition films selectively recognized BtOMe (LOD = 12.5 ng/mL) and biotinylated biomolecules, as shown by the stability constant K-s values (MIPA-U = 1442 and MIPNMU-U = 1502 M-1). The porous network generated in the polymer films by the flickering-cluster-like complexes present in the ni-DES facilitates the analyte diffusion and recognition. We propose this ni-DES as an economically advantageous and environmentally friendly alternative to conventional ionic liquids and organic solvents in polymer synthesis and to influence polymer morphology for developing hierarchical materials.

Electroorganic synthesis is a powerful sustainable tool for achieving greener and more efficient chemical processes across various industries. By adhering to the principles of green chemistry, atom economy, and resource efficiency, electroorganic synthesis can play a pivotal role in addressing environmental concerns and promoting a more sustainable future for chemical production. This review focuses on the latest advancements in the emerging application of electrochemistry in C-N bond formation through C-H/N-H cross-coupling. The first part of the review describes the electrochemical amination of arenes using metal catalysis (Cu, Co, Ni) with directing groups on the arene moiety. The next section addresses the same type of electrochemical C-N bond formation on arenes without directing groups, which represents a more general strategy enabling the synthesis of anilines and various heterocyclic-bound arenes in high yields. Further developments on benzylic systems are also discussed. This is followed by developments in the combination of photocatalysis and electrochemistry to activate C-H bonds in arenes, alkanes, and benzylic systems, including the use of flow reactor configurations for these reactions.

Unsymmetrical urea derivatives are essential structural motifs in a wide array of biologically significant compounds. Despite the well-established methods for synthesizing symmetrical ureas, efficient strategies for the synthesis of unsymmetrical urea derivatives remain limited. In this study, we present a novel approach for the synthesis of unsymmetrical urea derivatives through the coupling of amides and amines. Utilizing hypervalent iodine reagent PhI(OAc)2 as a coupling mediator, this method circumvents the need for metal catalysts, high temperatures, and inert atmosphere. The reaction proceeds under mild conditions and demonstrates broad substrate scope, including various primary and secondary amines and primary benzamides. This protocol not only offers a practical and versatile route for synthesizing unsymmetrical ureas but also shows significant potential for the late-stage functionalization of complex molecules in drug development.