Melatonin is an ancient molecule that can be traced back to the origin of life. Melatonin's initial function was likely that as a free radical scavenger. Melatonin presumably evolved in bacteria; it has been measured in both α-proteobacteria and in photosynthetic cyanobacteria. In early evolution, bacteria were phagocytosed by primitive eukaryotes for their nutrient value. According to the endosymbiotic theory, the ingested bacteria eventually developed a symbiotic association with their host eukaryotes. The ingested α-proteobacteria evolved into mitochondria while cyanobacteria became chloroplasts and both organelles retained their ability to produce melatonin. Since these organelles have persisted to the present day, all species that ever existed or currently exist may have or may continue to synthesize melatonin in their mitochondria (animals and plants) and chloroplasts (plants) where it functions as an antioxidant. Melatonin's other functions, including its multiple receptors, developed later in evolution. In present day animals, via receptor-mediated means, melatonin functions in the regulation of sleep, modulation of circadian rhythms, enhancement of immunity, as a multifunctional oncostatic agent, etc., while retaining its ability to reduce oxidative stress by processes that are, in part, receptor-independent. In plants, melatonin continues to function in reducing oxidative stress as well as in promoting seed germination and growth, improving stress resistance, stimulating the immune system and modulating circadian rhythms; a single melatonin receptor has been identified in land plants where it controls stomatal closure on leaves. The melatonin synthetic pathway varies somewhat between plants and animals. The amino acid, tryptophan, is the necessary precursor of melatonin in all taxa. In animals, tryptophan is initially hydroxylated to 5-hydroxytryptophan which is then decarboxylated with the formation of serotonin. Serotonin is either acetylated to N -acetylserotonin or it is methylated to form 5-methoxytryptamine; these products are either methylated or acetylated, respectively, to produce melatonin. In plants, tryptophan is first decarboxylated to tryptamine which is then hydroxylated to form serotonin.

The stimuli-responsive polypeptides have drawn extensive attention because of their promising applications in biotechnology considering their biocompatibility, biodegradability, and bioactivity. In this tutorial review, we summarize the most recent progress in this area, including thermo-, redox-, photo-, and biomolecule responsive polypeptides over the past decade. The design and synthesis of stimuli-responsive polypeptides will be briefly introduced. The correlation between the structure and properties, particularly the effects of polypeptide conformation, will be emphasized here. In addition, the applications of stimuli-responsive polypeptides in controlled drug release and tissue engineering are briefly discussed.

A series of new functional amino acids were prepared in high yield via thiol−ene Michael addition between L-cysteine and monomethoxy oligo(ethylene glycol) (OEG) functionalized methacrylates (OEG x MA) and acrylate (OEG x A). These OEGylated cysteine derivatives were converted into polymerizable N-carboxyanhydride (NCA) monomers using triphosgene. Subsequent ring-opening polymerization (ROP) of these NCA monomers gave a series of OEGylated poly-L-cysteine (poly-EG x MA-C or poly-EG x A-C) homopolypeptides. Depending on the length of OEG side chains, poly-EG x MA-C and poly-EG x A-C polypeptides displayed different solubility and secondary structure in water. More importantly, the obtained polypeptides can display reversible thermoresponsive properties in water when the x value is between 3 and 5. The synthetic strategy represents a highly efficient method to prepare nonionic functional polypeptides with tunable thermoresponsive properties.

Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, are a diverse class of compounds having complex structural features with many stereocenters.

The oxidation-responsive behaviors of OEGylated poly-L-cysteine homopolypeptides, that is, poly(L-EG(x)MA-C)n, were investigated. These poly-L-cysteine derivatives adopted mixed conformation in water, in which the β-sheet accounted for a significant proportion. Upon oxidation, the thioethers in polypeptide side chains were converted to polar sulfone groups, which triggered the secondary structure transition from β-sheet preferred conformation to random coil. Accordingly, the increase of side-chain polarity together with conformation changes increased samples' water solubility and cloud point temperature. Using mPEG45-NH2 as macroinitiator, we synthesized PEG45-b-poly(L-EG2MA-C)22 diblock copolymer via ring-opening polymerization (ROP) of L-EG2MA-C N-carboxyanhydride (NCA). The PEG45-b-poly(L-EG2MA-C)22 was able to self-assemble into spherical micelles in aqueous solution, and the micelles could undergo an oxidation-triggered disassembly due to the oxidation-responsive thioethers. Such a new class of oxidation-responsive polypeptides might provide a promising platform to construct inflammation targeting drug delivery systems.

The development of chemically recyclable polymers presents the most appealing solution to address the plastics' end-of-use problem. Despite the recent advancements, it is highly desirable to develop chemically recyclable polymers from commercially available monomers to avoid the costly and time-consuming commercialization. In this contribution, we achieve the controlled ring-opening polymerization (ROP) of biosourced δ-caprolactone (δCL) using strong base/urea binary catalysts. The obtained PδCL is capable of chemical recycling to δCL in an almost quantitative yield by thermolysis. Sequential ROP of δCL and L-lactide (L-LA) affords well-defined PLLA-b-PδCL-b-PLLA triblock copolymers, which behave as thermoplastic elastomers with excellent elastic recovery, tensile strength and ultimate elongation. The upcycling of PLLA-b-PδCL-b-PLLA to recover ethyl lactate and δCL with high yields is achieved by refluxing with ethanol and then distillation under reduced pressure.

Despite the great potential of biorenewable α-methylene-γ-butyrolactone (MBL) to produce functional, recyclable polyester, the ring-opening polymerization (ROP) of MBL remains a challenge due to the competing polymerization of the highly reactive exocyclic double bond and low-strained five-membered ring. In this contribution, we present the first organocatalytic chemoselective ROP of MBL to exclusively produce functional unsaturated polyester by utilizing a phosphazene base/urea binary catalyst. We show that delicate chemoselectivity can be realized by controlling the temperature and using selected urea catalysts. The obtained polyester can be completely recycled back to its monomer by chemolysis under mild conditions. Experimental and theoretical calculations provide mechanistic insights and indicate that the ROP pathway is kinetically favored by using urea with stronger acidity at low temperatures.

Over the past several years, organocatalyzed polymerization reactions have attracted considerable attention, and these efforts have led to major advances. A large number of organic compounds have been proven active for the polymerization of a large variety of monomers. In particular, phosphazene bases (PBs) are a family of extremely strong, non‐nucleophilic, and uncharged auxiliary bases, and have shown their remarkable potential as organocatalysts for the ring‐opening polymerization (ROP) of cyclic monomers. By deprotonation of weak acids or in combination with lithium cation, PBs significantly enhance the nucleophilicity of the initiator/chain‐end, thus allowing fast and usually controlled anionic polymerization. In this feature article, the recent advances in phosphazene‐catalyzed ROP of cyclic esters are summarized. This review is divided into three sections, including general features, design and synthesis, and catalytic applications. It aims to provide a critical analysis of PB‐mediated ROP systems and a useful guide for the further design of organocatalysts applied to polymer synthesis. An outlook is given at the end.