Abstract
We report the synthesis of M2NH3 which is a tetracationic analogue of our prototypical acyclic CB[n]-type molecular container M2. Both M1NH3 and M2NH3 possess excellent solubility in D2O and do not undergo intermolecular self-association processes that would impinge on their molecular recognition properties. Compounds M1NH3 and M2NH3 do, however, undergo an intramolecular self-complexation process driven by ion–dipole interactions between the ureidyl C=O portals and the OCH2CH2NH3 arms along with inclusion of one aromatic wall in its own hydrophobic cavity. The Ka values for M1NH3 and M2NH3 towards seven nucleotides were determined by 1H NMR titration and found to be quite modest (Ka in the 102–103 M−1 range) although M2NH3 is slightly more potent. The more highly charged guests (e.g. ATP) form stronger complexes with M1NH3 and M2NH3 than the less highly charged guest (e.g. ADP, AMP). The work highlights the dominant influence of the ureidyl C=O portals on the molecular recognition behaviour of acyclic CB[n]-type receptors and suggests routes (e.g. more highly charged arms) to enhance their recognition behaviour towards anions.
Highlights
Since the pioneering work of Pedersen, Lehn, and Cram more than 40 years ago the development of the field of supramolecular chemistry has witnessed the creation ever more complex receptor molecules whose structures are tailored toward specific molecular targets.[1]
We have reported the synthesis of the tetracationic analogue of M2 which we refer to as M2NH3
We find that both M1NH3 (250 mM) and M2NH3 (≥ 207 mM) possess outstanding solubility in D2O
Summary
Since the pioneering work of Pedersen, Lehn, and Cram more than 40 years ago the development of the field of supramolecular chemistry has witnessed the creation ever more complex receptor molecules whose structures are tailored toward specific molecular targets.[1]. M1 and its relatives have been used in a variety of applications including the solubilization of insoluble pharmaceutical agents and carbon nanotubes, the creation of sensing ensembles, and the in vivo reversal of neuromuscular block.[24,25,26] We have studied the influence of several structural variables (e.g. aromatic sidewall identity, solubilizing group identity (NH3+ versus OH versus SO3Na), and length of central glycoluril oligomer (monomer – tetramer)) on their function as solubilizing excipients for insoluble drugs.[24,25,26] Interestingly, in our study of the recognition properties of the cationic analogue of M1 (M1NH3, Figure 1) we found that the container is not a good host for cationic compounds due to self-complexation of the NH3+ arms at the ureidyl carbonyl portals, but displayed modest affinity toward adamantanecarboxylate (Ka = 678 M−1) in 20 mM sodium phosphate buffer at pH 7.4.26 it appeared that the cationic arms turned M1NH3 into an anion receptor.
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