Metal–Ligand Interactions in Molecular Imprinting

Abstract

Molecular imprinting enables the design of highly crosslinked polymeric materials that are able to mimic natural recognition processes. Molecularly imprinted polymers exhibit binding sites with tailored selectivity toward target structures ranging from inorganic ions to biomacromolecules and even viruses or living cells. The choice of the appropriate functional monomer, crosslinker, and the nature and specificity of template-monomer interactions are critical for a successful imprinting process. The use of a metal ion mediating the interaction between the monomer and template (acting as ligands) has proven to offer a higher fidelity of imprint, which modulates the molecularly imprinted polymers (MIPs) selectivity or to endow additional features to the polymer, such as stimuli-responsiveness, catalytic activity, etc. Furthermore, limitations in using nonpolar and aprotic solvents are overcome, allowing the use of more polar solvents and even aqueous solutions as imprinting media, opening new prospects toward the imprinting of biomacromolecules (proteins, DNA, RNA, antibodies, biological receptors, etc.). This chapter aims to outline the beneficial pairing of metal ions as coordination centers and various functional ligands in the molecular imprinting process, as well as to provide an up to date overview of the various applications in chemical sensing, separation processes (stationary phases and selective sorbents), drug delivery, and catalysis.

Improved Enantioselectivity for Atenolol Employing Pivot Based Molecular Imprinting

“…The monomers are thus regularly positioned around the template via coordinate bonds restraining the free motion of the species. Consequently, the number of non-specific binding sites decreases, and improved imprinting factors are achieved [ 19 ]. Since chiral molecular recognition by MIPs relies on very small energetic differences between the forming transient selector/select and complexes at the polymer’s interaction sites, any improvement in the degree of order throughout the polymerization step is beneficial in conveying the template’s (i.e., target enantiomer) molecular information to the emerging MIP recognition sites with the highest possible fidelity.…”

Perspectives of Molecularly Imprinted Polymer-Based Drug Delivery Systems in Cancer Therapy

“…Rooted from these operational differences, the expected features (e.g., cross-linking, swelling degree) of the resulting imprinted polymers are discordantly ranked, implying certain constrains and limitations in the design space or even requiring different imprinting strategies (Table 1). The imprinting technology has been employed successfully in the development of MIP-based sorbents, stationary phases, sensor interface, or as alternative to biological antibodies and receptor systems [43][44][45][46][47], but the application of MIPs in drug delivery is still in its developing stage, in the in vitro proof of concept phase. However, MIPs possess a great potential for DDS use, due to some unique features compared to conventional polymers.…”

“…Their use however raises safety concerns if the polymer is intended for biomedical applications. An alternative in achieving high affinity imprinted sites in aqueous solutions is the metal ion coordination approach that employs a metal ion as a mediator in the formation of a ternary complex between the functional monomer, the metal ion, and the drug template [44]. The metal pivot interacts with the heteroatoms of the functional monomer and the template by accepting their electrons in order to fulfil its orbitals of the outer coordination sphere.…”

“…The nature of the metal ion is the most important parameter in order to achieve a high imprinting factor, however it needs to satisfy some prerequisites for drug delivery applications; the metal ion should not hamper the polymerization process, it must have a known coordination behavior such as the most favorable template, metal ion, and monomer interactions to be achieved, and most importantly to be non-toxic. The list of metals that have been used in the imprinting process as pivots is quite short, being restricted to several transitional metals such as: Co(II), Co(III), Cu(II), Ni(II), Zn(II), Cd(II), Fe(II), and Fe(III) [44]. Cadmium does not occur naturally in biological systems and is an exceptionally toxic heavy metal [79], thus it cannot be used in DDS development.…”

Molecularly imprinted cryogel cartridges for the selective recognition of tyrosine

“…Recently, molecular imprinting technology has been used in various fields such as chromatography, recognition, purification, separation, and drug delivery. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Tyr-imprinted beads, [27][28][29] electrochemical, 30 and voltammetric sensors 31…”