polymers Review Thiophene-Based Trimers and Their Bioapplications: An Overview Lorenzo Vallan 1,† , Emin Istif 2,† , I. Jénnifer Gómez 3,† , Nuria Alegret 4, * and Daniele Mantione 2, *   Citation: Vallan, L.; Istif, E.; Gómez, I.J.; Alegret, N.; Mantione, D. Thiophene-Based Trimers and Their Bioapplications: An Overview. Polymers 2021, 13, 1977. https://doi. org/10.3390/polym13121977 Academic Editor: Hiromasa Goto Received: 18 May 2021 Accepted: 12 June 2021 Published: 16 June 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Laboratoire de Chimie des Polymères Organiques (LCPO—UMR 5629), Université de Bordeaux, Bordeaux INP, CNRS F, 33607 Pessac, France;Lorenzo.Vallan@enscbp.fr 2 Department of Mechanical Engineering, Koç University, Rumelifeneri Yolu, Sarıyer, Istanbul 34450, Turkey; eistif@ku.edu.tr 3 Department of Condensed Matter Physics, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic; gomez.perez@ceitec.muni.cz 4 POLYMAT and Departamento de Química Aplicada, University of the Basque Country, UPV/EHU, 20018 Donostia-San Sebastián, Spain * Correspondence: nuria.alegret@ehu.es (N.A.); daniele.mantione@u-bordeaux.fr (D.M.) † These authors contributed equally to the work. Abstract: Certainly, the success of polythiophenes is due in the first place to their outstanding electronic properties and superior processability. Nevertheless, there are additional reasons that contribute to arouse the scientific interest around these materials. Among these, the large variety of chemical modifications that is possible to perform on the thiophene ring is a precious aspect. In particular, a turning point was marked by the diffusion of synthetic strategies for the preparation of terthiophenes: the vast richness of approaches today available for the easy customization of these structures allows the finetuning of their chemical, physical, and optical properties. Therefore, terthiophene derivatives have become an extremely versatile class of compounds both for direct application or for the preparation of electronic functional polymers. Moreover, their biocompatibility and ease of functionalization make them appealing for biology and medical research, as it testifies to the blossoming of studies in these fields in which they are involved. It is thus with the willingness to guide the reader through all the possibilities offered by these structures that this review elucidates the synthetic methods and describes the full chemical variety of terthiophenes and their derivatives. In the final part, an in-depth presentation of their numerous bioapplications intends to provide a complete picture of the state of the art. Keywords: conjugated polymers; polythiophenes; terthiophenes; thiophene trimers; biosensing; photosensitizers 1. Introduction Today, conductive polymers have become inalienable components of a wide spectrum of advanced technologies, including sensor and biosensors, batteries, solar cells, LEDs, and organic transistors [1–6]. Among conductive polymers, poly(3,4-ethylenedioxothiophene) (PEDOT) is undoubtedly the most widespread. In fact, a set of useful properties, such as high conductivity, superior photostability, low redox potential, transparency, and good processability, contributes to the exceptionality of this polymer [7]. Typically purchased as a water dispersion of PEDOT:PSS (poly(styrene)sulfonate), PEDOT is cheap and readily available for research purposes. As an alternative, PEDOT can be easily prepared by poly- merization from the EDOT monomer, allowing the preparation of films on a wide range of substrates. While for the above-mentioned reasons PEDOT was quickly establishing itself as the gold standard of conductive polymers, the progress in organic synthesis gradu- ally disclosed new possibilities for the easier preparation and modification of alternative thiophene-based structures, including thiophene and EDOT monomers carrying different functional groups. Therefore, a new research branch focused on the preparation of more Polymers 2021, 13, 1977. https://doi.org/10.3390/polym13121977 https://www.mdpi.com/journal/polymers