Mechanically Interlocked Molecules for Biomedical Applications

Abstract

Mechanically interlocked molecules (MIMs) carry great potential in different fields of chemistry, based on their specific structures, their internal dynamics, their stimuli‐responsive behavior, and other unique features of the mechanical bond. This minireview presents some of the most recent developments in their use for medical and biological applications. For example, they have been used to influence, enhance or block the action of therapeutic agents to enable targeted drug delivery. The dynamic structural properties have been used to generate switches and transporters, as well as sensors for various medically relevant species. Building MIMs by incorporating biomolecules like DNA and proteins has served as a novel way to control their properties.

A rotaxane-based platform for tailoring the pharmacokinetics of cancer-targeted radiotracers

“…Supramolecular systems and mechanically interlocked molecules (MIMs) present interesting opportunities in the design of diagnostic imaging agents and therapeutic drugs. 15,[18][19][20][21][22][23][24][25][26] Supramolecular platforms have been shown to be viable routes for the synthesis of disease-targeted imaging probes, with key features including synthetic flexibility, rapid synthesis, facile labelling, water solubility, and biocompatibility of the construct. Here, we used mechanical bonding to make a supramolecular rotaxane-based 89 Zr-radiolabelled mAb for PET imaging of the human hepatocyte growth factor receptor (c-MET) and evaluated the impact of the non-covalent design on the radiotracer pharmacokinetics in vivo.…”

The Role of Dethreading Process in Pseudorotaxanes and Rotaxanes towards Advanced Applications: Recent Examples

“…[1][2][3] Within the range of intertwined compounds, rotaxanes are postulated as ideal candidates for the design of molecular machines, developing applications in a wide range of fields, [4][5][6] such as catalysis, [7][8][9][10][11][12][13][14] materials science [15][16][17][18][19][20][21][22][23][24] or medicinal chemistry. [25][26][27] Usually, the design of these structures seeks the stability of the mechanical bond, thus preventing the dissociation of the different components in order to carry out a specific function. However, as it occurs in many biological processes, in which the mechanical bond is temporarily formed to undertake a precise function (such as the biological molecular machine processive catalysts), sometimes the design of these molecules requires the rational incorporation of certain functionalities which allow the dethreading of the counterparts by applying different stimuli.…”

Fluorinated [2]rotaxanes with spirofluorene motifs: a non-symmetric distribution of the ring component along the axle component

“…1,2 The potential applications of these MIMs in general and rotaxanes in particular in various fields like nanoelectronics, polymer chemistry, catalysis and medical science are continuously increasing their traction. [3][4][5][6][7] Accordingly, many synthetic methodologies like template synthesis, self-assembly, or metal mediated coupling reactions were developed to access these attractive targets through efficient ways. 8 In addition to their alluring structural and physio-chemical attributes, control of the distribution of components in rotaxanes has been studied thoroughly to understand their dynamic behavior and elaborated further to develop stimuli-responsive molecular systems.…”

“…1,2 The potential applications of these MIMs in general and rotaxanes in particular in various fields like nanoelectronics, polymer chemistry, catalysis and medical science are continuously increasing their traction. 3–7 Accordingly, many synthetic methodologies like template synthesis, self-assembly, or metal mediated coupling reactions were developed to access these attractive targets through efficient ways. 8…”