The most used reaction among the plethora of the thiol chemistry reactions in polymer science is the thiol-ene reaction, which is also considered a click reaction. The number of publications reporting the use of thiol groups or related to the synthesis and postpolymerization modification of polymers and materials with specific and advanced features is increasing rapidly. Indeed, thiol chemistry plays an important role in polymer science. Therefore, a good functional group, once added, should allow for a wide range of modifications and open the way to diverse applications: the great versatility of the thiol chemistry can ensure this flexibility. However, because of the reactivity of the polyester backbone, which can undergo hydrolytic degradation with a consequent drop in the molecular weight and change of the physical properties of the material, the controlled introduction of functional moieties requires some synthetic effort. Therefore, methods to integrate amino, carboxyl, hydroxyl, allyl and many other functionalities onto aliphatic polyester chains for fine-tuning of their physical and biological properties have been sought, and review papers are available in the literature.

Indeed, for applications in the biomedical field, such as tissue engineering and drug delivery, a functional group could provide an anchoring site for biologically active ligands, thus improving cell adhesion and function, or allow the preparation of degradable particles and polymeric networks with controlled dimension and function. The synthesis of polyesters susceptible to further modifications is highly desired since the presence of functional groups could allow for tuning the physical and mechanical properties, for example, the rate of hydrolysis, degree of crystallinity, melting point, glass transition temperature, and processability, as well as to improve hydrophilicity and biocompatibility. However, while their physical properties can be tailored via copolymerization, a major limitation toward application in new areas results from the lack of readily accessible side-chain functionalities. Īmong the degradable polymer classes utilized in the biomedical field, the aliphatic polyesters have a leading position. From the polymer chemistry standpoint, this customization means the designing of efficient synthetic approaches to the manipulation of the polymer structure, modulating the physical properties and integrating active tags that can foster cellular interactions. The results indicate that some aspects of the amide bond and proper distance between this amide and the thiol/thioester moiety are critical for activity of CoA ester-utilizing enzymes.The advancements in the use of degradable polymers in the biomedical field rely on the possibility of customizing the properties of the device to match the application needs. Analogues of several CoA thioesters in which the amide bond was replaced with a hemithioacetal linkage exhibited no measurable activity with the appropriate enzymes. An analogue in which an extra methylene group was inserted between the amide bond and the thiol group showed less than 4-fold diminished binding to the three enzymes but exhibited less than 1% activity relative to acetyl-CoA with carnitine acetyltransferase and no measurable activity with the other two enzymes. An analogue of acetyl-CoA in which this amide bond is replaced with an ester linkage was a good substrate for the enzymes carnitine acetyltransferase, chloramphenicol acetyltransferase, and citrate synthase, with K(m) values 2- to 8-fold higher than those of acetyl-CoA and V(max) values from 14 to >80% those of the natural substrate. Analogues of coenzyme A (CoA) and of CoA thioesters have been prepared in which the amide bond nearest the thiol group has been modified.

Thiol functional group