Metal-free click polymerizations rewrite the rules of step-growth polymerization

For nearly a century, step-growth polymerization has lived under the shadow of the Carothers–Flory theory, which demands near-perfect stoichiometric balance between bifunctional monomers and conversion above 99 percent before useful molecular weights emerge. A new open-access review in Discover Chemistry by Lukmanul Hakim Samada and Amru Daulay of Indonesia’s National Research and Innovation Agency argues that click chemistry has quietly dismantled these classical constraints, opening a path toward sustainable, on-demand degradable plastics. The review systematically compares copper-catalyzed azide-alkyne cycloaddition (CuAAC), thiol-yne, and spontaneous amino-yne click polymerizations, presenting them as three generations of an evolving synthetic philosophy rather than isolated techniques.

The classical limitations of step-growth polymerization are well documented. Even minor stoichiometric imbalances, caused by monomer loss or side reactions, drastically reduce the number-average degree of polymerization. The most probable molecular weight distribution yields a dispersity approaching 2, with no built-in mechanism for narrowing it. Many reactive functional groups, such as amines and alcohols, interfere with catalysts or trigger unwanted side reactions, and conventional polycondensations often require extended reaction times, elevated temperatures, vacuum, or azeotropic distillation. Previous strategies to escape these limits include converting step-growth into chain-growth behavior by increasing end-group reactivity, as demonstrated by Yokoyama and Yokozawa, and Friedel-Crafts polycondensation approaches developed by Zou and co-workers that achieve molecular weight control without strict stoichiometric balance.

CuAAC, discovered independently by Sharpless and Meldal in 2002, represents the first generation of click polymerization. The accepted mechanism involves two copper atoms: copper first coordinates to the terminal alkyne and, after base-assisted deprotonation, forms a copper-acetylide complex in the rate-determining step with an activation energy of 50 to 70 kilojoules per mole. The azide then coordinates to a second copper atom in a bent geometry of roughly 120 degrees, the copper-acetylide attacks the terminal nitrogen to form a six-membered metallacycle, and ring contraction followed by protonolysis releases the 1,4-disubstituted 1,2,3-triazole product with greater than 99 percent regioselectivity. Ligands such as PMDETA and TBTA stabilize Cu(I) against oxidation, increase solubility, and prevent the formation of inactive clusters, while polar aprotic solvents like DMF and DMSO give the highest rates. El-Hamshary and colleagues showed that CuAAC click polymerization achieves more than 90 percent functionalization efficiency within four hours at room temperature, although metal residues exceeding 500 parts per million of copper remain a serious concern for biomedical applications.

Thiol-yne click polymerization, the second generation, eliminates the metal catalyst entirely. Under UV irradiation between 250 and 365 nanometers, the reaction proceeds through a radical chain mechanism: a photoinitiator such as DMPA undergoes homolytic cleavage to generate radicals, the resulting thiyl radical adds to the alkyne in an anti-Markovnikov fashion with an activation energy of 40 to 60 kilojoules per mole, and the vinyl sulfide radical abstracts a hydrogen from another thiol molecule to propagate the chain. Crucially, the vinyl sulfide intermediate still contains a double bond, and a second, slower thiyl radical addition follows, with the rate ratio between the first and second additions typically between 3 and 10. This sequential addition kinetics is a conceptual breakthrough, because it shows that rate differentiation enables controlled network formation with uniform structures and higher crosslink density than thiol-ene chemistry allows. The radical pathway produces anti-Markovnikov addition with 60 to 80 percent trans stereocontrol, since the trans isomer sits 5 to 10 kilojoules per mole lower in energy than the cis form.

For thick samples or large-scale production exceeding one kilogram, the UV requirement limits scalability, so the review highlights an alternative base-catalyzed pathway using organobases such as DMAP or triethylamine at 1 to 10 mole percent loading. Here the base deprotonates the thiol to form a thiolate anion, which adds to the electron-deficient alkyne via Michael addition, and the resulting vinyl sulfide anion abstracts a proton from another thiol to regenerate the thiolate. DMAP proves more effective than triethylamine because its conjugate acid is more stable, making it a better nucleophile. The base-catalyzed route works in open air and reaches 80 to 85 percent conversion, somewhat below the greater than 90 percent achieved under UV, but it avoids the oxygen exclusion that the radical pathway demands, since oxygen scavenges radicals and cuts reaction rates by 50 to 80 percent in air.

The third generation, spontaneous amino-yne click polymerization, requires no catalyst, initiator, or external energy input at all. Tang’s group demonstrated the synthesis of regio- and stereospecific poly(beta-aminoacrylate)s by reacting activated propiolates with aliphatic amines at room temperature. The mechanism, elucidated through DFT calculations and kinetic studies, begins when the amine lone pair attacks the beta-carbon of the electron-deficient alkyne, whose electron-withdrawing group lowers the LUMO energy from roughly minus 0.5 electronvolts for an unsubstituted alkyne to between minus 1.5 and minus 2.0 electronvolts. A zwitterionic intermediate forms and is stabilized by resonance, a fast proton transfer of only 10 to 20 kilojoules per mole occurs through a six-membered transition state, and tautomerization yields the enamine product with greater than 95 percent trans selectivity. The trans preference arises from minimized electrostatic repulsion in the zwitterionic intermediate and a thermodynamic advantage of 10 to 15 kilojoules per mole over the cis isomer. Reported activation energies of 35 to 45 kilojoules per mole are significantly lower than CuAAC’s 50 to 70, and electron-withdrawing groups increase reaction rates by 10 to 50 fold. The reaction reaches more than 95 percent conversion in 0.5 to 2 hours at room temperature in open air with a strict 1:1 amine-to-alkyne ratio and no excess required.

The reversible enamine bonds formed in amino-yne chemistry carry particular significance for materials design. Hydrogels produced through this route undergo reversible sol-gel transitions induced by pH, because the enamine bonds are acid-sensitive and preserve an equilibrium between amine, enamine, and aldehyde groups, suggesting applications in tissue engineering and stimuli-responsive biodegradable systems. Zhang’s group extended the chemistry to metallacycle-crosslinked supramolecular polymers with elastomer characteristics, enhanced mechanical strength, and self-healing behavior. The review also covers RAFT step-growth copolymers, which combine the functional group tolerance of controlled radical polymerization with step-growth versatility for drug delivery applications, and one-pot hyperbranched star copolymers synthesized by Bang and co-workers, who used rigorous mathematical derivation and proton NMR spectroscopy to quantify intramolecular cyclization defects in a single batch.

Perhaps the most consequential application discussed is the photodegradable precision polyketone. Commercial polyketones typically contain fewer than 5 ketone groups per 1000 methylene units, but ADMET step-growth polymerization can incorporate one ketone per 19th methylene unit, equivalent to 52 ketones per 1000 methylene units, with every ketone isolated from its neighbors by at least 18 methylene units. This regular spacing prevents crosslinking side reactions and ensures that Norrish type II cleavage occurs at every ketone, leading to complete backbone scission under appropriate conditions. The theoretical basis lies in orbital energetics: ketones exhibit a HOMO-LUMO gap of roughly 4.0 to 4.5 electronvolts, below the 4.5 electronvolt threshold needed for photochemical excitation, whereas esters exceed 5.0 and amides exceed 5.5 electronvolts, explaining why polyketones are photodegradable while polyesters and polyamides are not. These ADMET-derived polymers degrade under UV irradiation of at least 300 watts per square meter with half-lives of 7 to 20 days under accelerated conditions, and their glass transition temperature can be tuned from minus 20 to 150 degrees Celsius by varying monomer structure, from aliphatic to aromatic diamines.

Yet the review delivers a pointed caution on the popular claim of microplastic-free degradation. Complete backbone scission occurs only under controlled accelerated UV conditions with intensity of at least 300 watts per square meter, wavelengths of 254 to 365 nanometers, an aerobic atmosphere, and temperatures of at least 15 degrees Celsius, yielding small-molecule products such as aldehydes, ketones, and carboxylic acids with molecular weights below 1000 daltons. Under natural weathering, where UV intensities typically range from 10 to 50 watts per square meter, Norrish type II cleavage may be incomplete, potentially leaving higher molecular weight fragments that qualify as microplastics. Anaerobic environments such as marine sediments and landfills would substantially slow or prevent complete degradation, and comprehensive ecotoxicological testing of the degradation products according to OECD guidelines has not yet been performed. The authors conclude that regular chromophore spacing matters more than chromophore concentration for complete photodegradation, that metal-free click polymerizations achieve efficiency comparable to CuAAC while eliminating cytotoxicity, and that external energy input can be systematically reduced to zero through monomer electronic design. Before industrial adoption, however, natural weathering studies, standardized toxicity assays, and cost reduction strategies, including cheaper alternatives to Grubbs catalysts that currently exceed 500 dollars per gram, must take priority.

Subject of Research: Chemistry

Article Title: Thiol-yne and amino-yne click polymerizations advance step-growth polymerization toward sustainable and photodegradable polymers

Article References: Samada, L. H., & Daulay, A. (2026). Thiol-yne and amino-yne click polymerizations advance step-growth polymerization toward sustainable and photodegradable polymers. Discover Chemistry, 3(1), Article 434. https://doi.org/10.1007/s44371-026-00901-4

Image Credits: AI Generated

DOI: 10.1007/s44371-026-00901-4

Keywords: click chemistry, step-growth polymerization, thiol-yne, amino-yne, CuAAC, polyketones, photodegradable polymers, ADMET, microplastics, sustainable polymers, Norrish type II, green chemistry