**4. Conclusions**

In this work, the synthesis of a nature-inspired antifouling compound (GAP) was optimized to maximize GAP production. GAP was obtained with the same purity as the previous methods and with better yields in only 1 h under MW irradiation. This more reproducible, feasible and greener synthesis will certainly allow an easier scale-up synthesis of GAP for future in situ studies and commercialization. MW irradiation is an established way to speed up chemical syntheses, and dominates the pharmaceutical industry, as it improves the homogeneity of the synthesis. Using a parallel scale-up approach, it is possible to achieve scalability for potential industrial adoption by using several vessels simultaneously. Furthermore, it is expected that this technology can increase the overall efficiency of organic synthesis in an environmental friendly way. On the other hand, the obtention of the raw material gallic acid, through the valorization of winery waste by a green extraction method, will also be considered in the future.

Additionally, the several analytical methods developed during this work, using ion pairing chromatography and WAX, provided important contributions to the analysis of sulfated and highly polar compounds in water.

Moreover, the potential of this very polar compound to be applied as an antifouling additive in polymeric coating systems has been proven by its successful immobilization in marine coatings, using a non-leaching strategy promoted by the incorporation of the TZA crosslinker. This triaziridine functional crosslinker reacted with the active hydrogen of the carboxyl function in the GAP structure, thus acting as a bridge molecule between the coating components and GAP. Furthermore, the GAP-based coatings seem to keep their bioactivity, at least regarding the fixation of mussel larvae. These results encourage further in situ studies with GAP as an AF additive in coatings, and an in-depth characterization of the final physical–chemical properties of coatings obtained.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1660-3397/18/10/489/s1, Table S1: Linear regression and sensitivity data, Table S2: Accuracy, intra- and inter-day variability (precision), Figure S1: Representative chromatograms of 200 μM of GAP obtained by conventional (green line) and new optimized synthesis (black line), Figure S2: DFT optimized structures of GAP and TZA (ADF/BP86/TZ2P), Figure S3: 1H NMR spectra of gallic acid persulfate (GAP, green line), triaziridine crosslinker (TZA, black line) and GAP–TZA derivative (brown line) in DMSO-*d6* at 293 K, Figure S4: 13C APT NMR spectrum of gallic acid persulfate (GAP) in DMSO-*d6* at 293 K, Figure S5: 13C APT NMR spectrum of triaziridine propionate crosslinker (TZA) in DMSO-*d6* at 293 K, Figure S6: 13C APT NMR spectrum of GAP–TZA derivative in DMSO-*d6* at 293 K, Figure S7: Representative PVC coated plates with commercial marine coatings, from left to right: PU (polyurethane-based control); GAP-CI/PU (PU-based coating containing chemically immobilized (CI) gallic acid persulfate, GAP; PDMS (polydimethylsiloxane-based control); and GAP-CI/PDMS (PDMS-based coating containing CI GAP. Figure S8: Representative chromatograms of 500 μM of GAP dissolved in UPW before and after being passed through the

cartridge, Figure S9: Representative chromatograms of 100 μM of GAP dissolved in UPW before and after being passed through the cartridge.

**Author Contributions:** Conceptualization, E.R.S. and M.C.-d.-S.; data curation, C.V.-B. and F.C.; formal analysis, C.V.-B., S.C. and M.J.C.; funding acquisition, M.C.-d.-S.; investigation, C.V.-B., F.C., B.P., J.R.A. and E.R.S.; methodology, E.S., M.M.M.P., V.V., J.R.A., E.R.S. and M.C.-d.-S.; project administration, M.C.-d.-S. and E.R.S.; resources, M.M.M.P., M.J.C., V.V. and E.R.S.; supervision, J.R.A., E.R.S. and M.C.-d.-S.; validation, C.V.-B. and F.C.; visualization, C.V.-B.; writing—original draft, C.V.-B., J.R.A., E.R.S. and M.C.-d.-S.; writing—review and editing, C.V.-B., E.S., M.M.M.P., M.J.C., V.V., J.R.A., E.R.S. and M.C.-d.-S. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by national funds through the Foundation for Science and Technology (FCT) within the scope of research unit grants to CIIMAR (UIDB/04423/2020 and UIDP/04423/2020), to BioISI (UIDB/04046/2020 and UIDP/04046/2020) and under the project PTDC/AAG-TEC/0739/2014 (reference POCI-01-0145-FEDER-016793) supported through national funds provided by FCT and the European Regional Development Fund (ERDF) via the Programa Operacional Factores de Competitividade (POFC/COMPETE) programme and the Reforçar a Investigação, o Desenvolvimento Tecnológico e a Inovação (RIDTI; project 9471).

**Acknowledgments:** C.V.B. acknowledges FCT for the scholarship SFRH/BD/136147/2018. E.R.S. thanks FCT for her work contract through the Scientific Employment Stimulus—Individual Call—CEECIND/03530/2018.

**Conflicts of Interest:** The authors declare no conflict of interest.
