Nature-Inspired Peptide Antifouling Biocide: Coating Compatibility, Field Validation, and Environmental Stability

Abstract

This study reports the development of a class of eco-friendly antifouling biocides based on a cyclic dipeptide scaffold, 2,5-diketopiperazine (2,5-DKP). The lead compound cyclo(N-Bip-l-Arg-N-Bip-l-Arg) (1) was synthesized in gram amounts and used to assess the compatibility with an ablation/hydration coating, efficacy against biofouling, and biodegradation. Leaching of 1 from the coating into seawater was assessed via a rotating drum method, revealing relatively stable and predictable leaching rates under dynamic shear stress conditions (36.1 ± 19.7 to 25.2 ± 9.1 ng–1 cm–2 day–1) but low or no leaching under static conditions. The coatings were further analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS), with 1 seen to localize at the surface of the coating in a surfactant-like fashion. When coatings were deployed in the ocean, detectable reductions in biofouling development were measured for up to 11 weeks. After this time, biofouling overwhelmed the performance of the coating, consistent with leaching kinetics. Biodegradation of 1 in seawater was assessed using theoretical oxygen demand and analytical quantification. Masking effects were observed at higher concentrations of 1 due to antimicrobial properties, but half-lives were calculated ranging from 13.4 to 16.2 days. The results can rationally inform future development toward commercial antifouling products.

Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry

“…Nonoptimized release profiles (or even a lack of release data) combined with limited insights into paint composition and compound distribution often make it challenging to explain why a promising lead from the laboratory fails to function in the field. Several of our lead compounds have been studied in the field, with greatly ranging results. , Both synthetic analogs of phidianidine and a lead 2,5-DKP were shown to display detectable reductions in biofouling development. The phidianidine analog efficiently prevented microfouling for up to 84 days (duration of the study) but with no effect against macrofoulers (Figure ).…”

“…After this time, biofouling overwhelmed the performance of the coating, consistent with leaching kinetics that suggest a rapid depletion of the active antifouling ingredient (Figure ). It is not unlikely that the performance of both could be significantly improved with optimized paint/coating formulations.…”

“…(Top) 2,5-DKP paint distribution studies. (Left) ToF-SIMS analysis of a 2,5-DKP specific signal in different coatings before and after leaching experiments for 45 days . After the release experiment, no antifoulant is found in the coating, which suggests a rapid release and/or a surface enrichment, supported by dynamic ToF-SIMS analysis (right image) illustrating the coating stratigraphy with a clear surface enrichment of the active component.…”

“…(Bottom) Standard evaluation of coated panels at static/tidal sea conditions illustrating the evaluation of two promising leads, a phidianidine analog and a potent 2,5-DKP. Neither lead performed effectively in the field, illustrating the challenges involved in going from laboratory screens to field trials and coating formulations. , Adapted with permission from ref and . Copyright (2020 and 2023) American Chemical Society.…”

Proof of Concept of Natural and Synthetic Antifouling Agents in Coatings

“…Pérez et al reported the isolation and AF activity evaluation of five natural alkaloids from trees of the Atlantic rainforest, namely olivacine (60), uleine (61), and N-methyltetrahydroellipticine (62) from Aspidosperma austral, and the furoquinoline alkaloids kokusaginine (63) and flindersiamine (64) (Figure 2) from Balfourodendron riedelianum [54]. Alkaloids 62 and 63 displayed the most active anti-settlement activity against mussel M. edulis platensis [54].…”