Polymerization Unprecedented Acid-Promoted Polymerization and Gelation of Acrylamide: A Serendipitous Discovery Siew Yin Chan, [a, b] Shermin S. Goh, [b] Qingqing Dou, [b] Benjamin Qi Yu Chan, [b, c] Wee Sim Choo,* [a] David James Young,* [a, b, d] and Xian Jun Loh* [b, c, e] Abstract: Dilute acid polymerizes degassed, aqueous acryl- amide with concomitant gelation, without the need for added free radical initiator or cross-linking agent. This reac- tion is accelerated by sonication or UV irradiation, but inhib- ited by adventitious oxygen or the addition of a free radical inhibitor, suggesting an acid-accelerated free radical process. The resulting hydrogels are thixotropic in nature and partial- ly disrupted by the addition of chaotropic agents, indicating the importance of hydrogen bonding to the 3D network. This discovery was made while trying to prepare pectin-poly- acrylamide hydrogels. We observed that pectin initiated the gelation of acrylamide, but only if the aqueous pectin sam- ples had a pH lower than ca. 5. Hydrogels are cross-linked hydrophilic polymer-based materials with high water content and may absorb water up to thou- sands of times their dry weight. [1] They possess three-dimen- sional (3D) structures that resemble the extracellular matrix and have potential uses in biomedicine and personal care products. [2] Naturally derived polymers such as polysaccharides and proteins are of interest as components in hydrogels be- cause of their biocompatibility, biodegradability and potential for cell signalling. [3] However, naturally derived hydrogels are generally mechanically weak, can be inhomogeneous and are potentially immunogenic. [1] Synthetic hydrogels are generally stronger with tuneable degradation rates. [1, 3] Hydrogels com- bining the positive features of both would have potential for pharmaceutical, biomedical and personal care applications. We were therefore interested in the use of pectin as a natural polymer component for polyacrylamide hydrogels. Polyacrylamide is synthesized from acrylamide monomers by free radical polymerization, with or without added cross-link- ers. [4] While acrylamide is a neurotoxin, polyacrylamide is classi- fied as a safe material. The Food and Drug Administration (FDA) has approved of polyacrylamide as a denture adhesive, a polymer adjuvant for food treatment and a film former for the imprinting of soft-shell gelatin capsules if there is less than 0.2 % of acrylamide monomer content. The Cosmetic Ingredi- ent Review (CIR) Expert Panel also permits the use of polyacryl- amide containing less than 5 ppm acrylamide in cosmetic for- mulations. [5] Polyacrylamide gel is used extensively in biochem- istry, [6] biotechnology, [7] forensic science, [8] genetics, [9] microbiol- ogy, [10] molecular biology [11] and virology. [12] It is also used for wastewater treatment, [13] oil recovery, [14] papermaking, [15] dermal fillers, [16] personal care products [17] and for various bio- medical applications. [18] Commercial high molecular weight polyacrylamide is obtained from conventional radical polymeri- zation. [19, 20] It can be made in aqueous solution, [21] in emul- sions, [22] in polar organic solvents [19] or solvent-free in bulk. [23] Polymerization by redox- or photo-initiators is generally pre- ferred over the use of thermal initiators because the reaction can be initiated at lower temperatures with better conversio- n. [21a, 24] Some initiators such as 2,2’-azo-bis(isobutyronitrile) (AIBN) can be activated thermally or photolytically. [25] In a recent trend, redox-initiators have also been used as photo-ini- tiators. [26] The use of ammonium persulfate (APS) as an initiator, N,N’-methylenebis(acrylamide) (MBA) as a cross-linking agent, and N,N,N’,N’-tetramethylethylenediamine (TEMED) as a cata- lyst are a common combination that permits polymerization of [a] S. Y. Chan, Dr. W. S. Choo, Prof. D. J. Young School of Science Monash University Malaysia Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor (Malaysia) E-mail : choo.wee.sim@monash.edu dyoung1@usc.edu.au [b] S. Y. Chan, Dr. S. S. Goh, Dr. Q. Dou, B. Q. Y. Chan, Prof. D. J. Young, Prof. X. J. Loh Institute of Materials Research and Engineering (IMRE) Agency for Science, Technology and Research (A*STAR) 2 Fusionopolis Way, #08-01 Innovis, Singapore 138634 (Singapore) E-mail : lohxj@imre.a-star.edu.sg [c] B. Q. Y. Chan, Prof. X. J. Loh Department of Materials Science and Engineering National University of Singapore 9 Engineering Drive 1, Singapore 117575 (Singapore) [d] Prof. D. J. Young Faculty of Science, Health, Education and Engineering University of the Sunshine Coast Maroochydore, Queensland 4558 (Australia) [e] Prof. X. J. Loh Singapore Eye Research Institute (SERI) 11 Third Hospital Avenue, Singapore 168751 (Singapore) Supporting information and the ORCID identification number(s) for the au- thor(s) of this article can be found under: https://doi.org/10.1002/asia.201800552. Chem. Asian J. 2018, 13, 1797 – 1804  2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1797 Full Paper DOI: 10.1002/asia.201800552