Linking two molecules to form a desired larger molecule routinely happens in chemistry labs, but sometimes it is not easy. The linking might require a lot of heat with undesirable side-effects or cannot be carried out in isolation, which, in turn, would produce undesirable by-products.  

Click chemistry, for which three scientists — Carolyn Bertozzi, Morten Meldal and Barry Sharpless — got the chemistry Nobel Prize for 2022, is a method of linking molecules in a practicable way. 

After Sharpless and Meldal, working separately, developed click chemistry in 2001, the field has grown, with applications in pharmaceuticals and material science, but has remained a phenomenon involving liquids.  

The Indian Institute of Science Education and Research (IISER), Thiruvananthapuramhas done some noteworthy work in click chemistry involving solids, which could give rise to a variety of new industrial applications. But first, how exactly does ‘click chemistry’ work? Suppose you want to link molecules A and B to make a larger molecule AB, and you find that A and B won’t link easily, you have a problem. But if you find two ‘complementary reactive groups’ (CRGs), say, x and y, which can be linked to A and B, your problem is solved. You link A to x and B to y and make them react, so that you have AzB, with the linker ‘z’ in the middle.   

In click chemistry, x and y are usually azide and alkyne. To put it simply, an azide is a functional group (molecule) of three nitrogen atoms, linked with double bonds; an alkyne is a functional group of two carbon atoms, hooked to each other with a triple bond. So, if A is linked to an azide and B to an alkyne, you can link A and B together using a triazole, the product of a reaction between azides and alkynes (examples of other CRGs that click with each other include thiol-alkene, diene-dienophile, and tetrazine-alkene).  

What happens to the azide and alkyne after the two molecules A and B are linked? Prof Kana M Sureshan of IISER, Thiruvananthapuram, explains thus: In the reaction, the azide and alkyne get converted to ‘triazole’ (a five-sided ring containing two carbon atoms and three nitrogen atoms), which bridges the two entities together. If an azide attached to an entity ‘A’ and an alkyne attached to an entity ‘B’ react, it gives a new molecule in which fragments A and B are bridged by the newly formed triazole-ring. So, there is no more azide or alkyne in the system after the reaction. The triazole cannot be got rid of; it is part of the new molecule synthesised.”  

The propensity of azides and alkynes to click together was discovered half a century ago by the German scientist Rolf Huisgen (who died at 99 in 2020), but the technique could not be used because it required 160 degrees C, at which temperature other problems arose.  Sharpless and Meldal, working separately, discovered in 2001 that the reaction can happen at room temperature, and in a better manner, with copper as catalyst — a reaction that is now famously known as ‘copper-assisted azide alkyne cycloaddition’. Bertozzi found a way of doing away with the toxic copper for bio applications, by ‘straining’ the alkyne into a ring — giving it energy like a spring — for the azide-alkyne cycloaddition reaction. This is immensely beneficial because, unlike other ways of linking two chemicals, the azide-alkyne method does not engender other competing reactions.   

IISER proves its mettle  

IISER has gone a step ahead, doing azide-alkyne cycloaddition in solid state. “Like Bertozzi’s strain-promoted azide-alkyne cycloaddition (SPAAC), our topochemical azide-alkyne cycloaddition (TAAC) requires no catalyst. This is achieved by organising azide and alkyne at a close proximity in the crystal lattice,” Sureshan told Quantum. In this crystal engineering, the designed molecules have to pack in such a way that the azide of one molecule and alkyne of another are placed close together, at a ready-to-react distance.  

Prof Sureshan’s team does polymerisation — making chains of monomers (identical molecules) — using TAAC. He explains: “We have designed monomers using carbohydrates, peptides and even nucleosides and polymerised them using our TAAC chemistry to get polysaccharide-mimics, protein-mimics, and DNA-mimics, respectively.”  

The excitement behind such polymerisation is that the result is crystalline polymers, which cannot be made by conventional methods. Crystallinity gives special properties to materials.  

Sureshan has achieved the synthesis of a crystalline material that can reversibly absorb water molecules from the atmosphere, making it a material that has huge potential for atmospheric water harvesting.  

IISER has synthesised several biopolymer-mimics, that have industrial applications. Right now, Sureshan is working on making bio-compatible materials for implants. A bone has a mesh of proteins into which inorganic phosphates are embedded, he explains. “We can use our chemistry to make protein-mimics as templates to embed phosphates.”  

Sureshan is also working on alkenes, instead of alkynes, which is possible in solid-state reactions. The result is ‘triazoline-linked polymers’, which are amenable to be worked on to yield a bouquet of functional polymers.  

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