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.

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.

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.

The regiochemical outcome of a cobalt(ii) catalysed C-H activation reaction of aminoquinoline benzamides with unsymmetrical 1,3-diynes under relatively mild reaction conditions can be steered through the choice of diyne. The choice of diyne provides access to either 3- or 4-hydroxyalkyl isoquinolinones, paving the way for the synthesis of more highly elaborate isoquinolines.

The growing demand for lithium-ion batteries (LiBs) for the electronic and automobile industries combined with the limited availability of key metal components, in particular cobalt, drives the need for efficient methods for the recovery and recycling of these materials from battery waste. Herein, we introduce a novel and efficient approach for the extraction of cobalt, and other metal components, from spent LiBs using a nonionic deep eutectic solvent (ni-DES) comprised of N-methylurea and acetamide under relatively mild conditions. Cobalt could be recovered from lithium cobalt oxide-based LiBs with an extraction efficiency of >97% and used to fabricate new batteries. The N-methylurea was found to act as both a solvent component and a reagent, the mechanism of which was elucidated.

Here we present an iridium catalysed C2-selective methylation of indoles using methyltrifluoroborate as a source of methyl group. The iridium catalyst selectively discriminates the indole C2 and C4 C-H bonds by coordination with a pivaloyl directing group.

Per-and polyfluoroalkyl substances (PFAS) are highly toxic pollutants of significant concern as they are being detected in water, air, fish and soil. They are extremely persistent and accumulate in plant and animal tissues. Traditional methods of detection and removal of these substances use specialised instrumentation and require a trained technical resource for operation. Molecularly imprinted polymers (MIPs), polymeric materials with predetermined selectivity for a target molecule, have recently begun to be exploited in technologies for the selective removal and monitoring of PFAS in environmental waters. This review offers a comprehensive overview of recent developments in MIPs, both as adsorbents for PFAS removal and sensors that selectively detect PFAS at environmentally-relevant concentrations. PFAS-MIP adsorbents are classified according to their method of preparation (e.g., bulk or precipitation polymerization, surface imprinting), while PFAS-MIP sensing materials are described and discussed according to the transduction methods used (e.g., electrochemical, optical). This review aims to comprehensively discuss the PFAS-MIP research field. The efficacy and challenges facing the different applications of these materials in environmental water applications are discussed, as well as a perspective on challenges for this field that need to be overcome before exploitation of the technology can be fully realised.