Creating spaces for defined chemical interactions: a new phosphorus-based supramolecule to spot chirality

In a recent paper in the journal Angewandte Chemie, Prof. R. Boomi Shankar’s group at IISER Pune described the design and synthesis of an amino-phosphonium supramolecule for the chiral recognition of a variety of chiral compounds.

Chirality is a property wherein the mirror image of an object cannot be fully superimposed on the object. Chiral objects have a certain handedness or asymmetry in their structure--the kind seen in the shell of snails. Biological molecules such as DNA, peptides, and enzymes are chiral. The two forms of a chiral molecule, referred to as enantiomers, possess similar physical and chemical properties, but usually show different biological properties.

The practical consequences of such differences in a pair of nearly-identical molecules are intriguing, especially when we learn of examples where one of the enantiomers promotes health while the other leads to disease. This makes chiral recognition not only a fascinating problem in chemistry, but also an important technique with potential applications.

 

Watch here an explanatory video produced by the IISER Pune Science Media Centre on this work

Supramoleculear and cage-like molecules, carefully designed and synthesised by supramolecular chemists, are a recent addition to the toolkit of chiral recognition. The space within such self-assemblies and the chemical moieties of the framework that open into them, when planned strategically, can offer selective and non-covalent binding opportunities with one of the enantiomers.

This aids in spotting the differences between the enantiomers, separating and purifying the enantiomers, and carrying out specific reactions which are otherwise not possible in open spaces.

The central theme in Prof. Boomi Shankar’s group at IISER Pune has been to make phosphorus-based compounds for applications in supramolecular and materials science. Used in conjunction with palladium-based clusters and in native form in some instances, these compounds can create architectures in the form of cages with pockets, and have a wide range of applications in the industry and in synthetic organic chemistry laboratories.

In the present paper, the group described the design and synthesis of one such phosphorus-based compound—an aminophosphonium salt-- and demonstrated that the enantiomeric pair of this compound can tell apart chiral molecules. 

Each enantiomer of the pair contains four chiral α-methyl benzyl amino substituents around the phosphorus center and a chloride ion to restore the charge balance in the molecule. Through spectroscopy and crystallography, the team confirmed the enantio-enriched nature of these salts.

The composition of this aminophosphonium salt, with four amino protons, chloride anion, aryl rings from the benzylic groups, allows it to engage in various non-covalent interactions with a set of chiral organic molecules the team tested.

The team then probed the selectivity of binding using spectroscopy techniques such as proton-NMR or UV-Visible titrations. They found that several of the host-guest pairs had very high binding selectivity, depending on the nature of interactions between them. Among the pairs, the one with R-isomer of 1-cyclohexylethyl amine displayed a remarkably high selectivity value using the R-isomer of the aminophosphonium salt as the host.

Through theoretical calculations on the host-guest pairs' energy-optimized structures, the team attributes this high selectivity to multiple interactions such as H-bonding, ion-dipole, and π-π interactions.

Speaking on the novelty of this work, Prof. Boomi Shankar said, “In comparison with our host materials, the receptors reported so far in the literature suffer from their high cost, synthetic challenges owing to their larger structures, complex recognition mechanisms, limited functional group access, and in certain instances, low selectivity. Typical methods of chiral recognition involve complex techniques such as X-ray crystallography, 2D-NMR, and chemical derivatization. This report demonstrates a simple ¹H-NMR and low-cost UV-Visible spectroscopic methods to detect the recognition of analytes in solution without derivatization.”

The team believes that the findings of this report will subsequently motivate the search for small-molecule based assemblies for the separation of enantiomers and the development of low-cost separation technologies.

This research was supported by a grant from the Science and Engineering Research Board (SERB), Govt of India.

Article Citation:

Prabhakaran Rajasekar, Cavya Jose, Meghamala Sarkar, and Ramamoorthy Boomishankar (2021). Effective enantioselective recognition by chiral amino‐phosphonium salts.  Angewandte Chemie International Edition 60, 4023–4027.

 

- Article edited by Dr. Shanti Kalipatnapu, with inputs from Prof. Boomi Shankar's group

- Video produced by IISER Pune's Science Media Centre in partnership with the Research Communications Office