Repeatable Perming via Thiol–Michael Click Reaction: Using Amide Derived from Maleic Acid and Cystine

Conventional perming relies on oxidative agents that significantly damage hair. The thiol-Michael click perming strategy derived from linear aliphatic diols and diamines has been developed to avoid oxidative damage, but lacks repeatable perming capabilities. In this study, a novel thiol-Michael click perming molecule was proposed for repeatable perming while avoiding oxidative damage. <i>N</i>,<i>N</i>'-bis(maleoyl)-l-cystine (MA2-CySS) was synthesized and characterized through Raman spectroscopy and ¹H NMR with MTT assay demonstrated no cytotoxicity up to 1000 μg/mL. Click reactivity analysis revealed that the reaction reached a plateau after 30 min, with alkaline pH and elevated temperatures significantly enhancing reactivity. MA2-CySS perming achieved efficiency comparable to oxidative perming, exceeding 1300% across three perming cycles. MA2-CySS perming significantly reduced both color change and cuticle damage, as demonstrated by color difference measurements and SEM, while maintaining superior mechanical properties as revealed by tensile property tests. Raman spectroscopy demonstrated that MA2-CySS perming better preserves hair keratin's secondary structure, maintaining superior <i>α</i>-helix content at 27.50% versus 24.35%, exhibiting higher disulfide bond retention at 85% versus 72%, and showing gauche-gauche-gauche to trans-gauche-trans conformational conversion at 9% versus 6%. This study demonstrates that repeatable perming via thiol-Michael click reaction represents a significant advancement in perming methodology.