Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry.

ConspectusThe unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.6% of global carbon emissions, highlighting the global scale and the importance of this problem. Improved antifouling strategies to limit surface colonization are paramount for essential activities such as shipping, aquaculture, desalination, and the marine renewable energy sector, representing both a multibillion dollar cost and a substantial practical challenge. From an ecological perspective, biofouling is a primary contributor to the global spread of invasive marine species, which has extensive implications for the marine environment.Historically, heavy metal-based toxic biocides have been used to control biofouling. However, their unwanted collateral ecological damage on nontarget species and bioaccumulation has led to recent global bans. With expanding human activities within aquaculture and offshore energy, it is both urgent and apparent that environmentally friendly surface protection remains key for maintaining the function of both moving and stationary marine structures. Biofouling communities are typically a highly complex network of both micro- and macroorganisms, representing a broad section of life from bacteria to macrophytes and animals. Given this diversity, it is unrealistic to expect that a single antifouling "silver bullet" will prevent colonization with the exception of generally toxic biocides. For that reason, modern and future antifouling solutions are anticipated to rely on novel coating technologies and "combination therapies" where mixtures of narrow-spectrum bioactive components are used to provide coverage across fouling species. In contrast to the existing cohort of outdated, toxic antifouling strategies, such as copper- and tributyltin-releasing paints, modern drug discovery techniques are increasingly being employed for the rational design of effective yet safe alternatives. The challenge for a medicinal chemistry approach is to effectively account for the large taxonomic diversity among fouling organisms combined with a lack of well-defined conserved molecular targets within most taxa.The current Account summarizes our work employing the tools of modern medicinal chemistry to discover, modify, and develop optimized and scalable antifouling solutions based on naturally occurring antifouling and repelling compounds from both marine and terrestrial sources. Inspiration for rational design comes from targeted studies on allelopathic natural products, natural repelling peptides, and secondary metabolites from sessile marine organisms with clean exteriors, which has yielded several efficient and promising antifouling leads.

Probing the correlation between corrosion resistance and biofouling of thermally sprayed metallic substrata in the field.

The correlation between inherent corrosion resistance and biofouling was investigated for five different metallic coatings. Steel panels thermally spray-coated with either aluminium, Monel, bronze or different aluminium alloys were tested in controlled salt mist conditions and electrochemical corrosion tests and subsequently employed at sea. The biofouling of the panels was monitored at different depths (5, 10 and 15 m) at periods ranging from 5 to 12 months. The main macrofouling organisms were quantified and analysed using permutational multivariate analysis. The results indicate a significant difference in fouling pressure between depths and the geographic sites used. No statistically significant link between high corrosion resistance and lower biofouling pressure was observed, indicating that the main marine macrofoulers settled equally well on corrosion resistant and corrosion prone metallic surfaces. This work sheds light on biofouling of thermally sprayed metallic substrata and it characterizes and compares biofouling assemblages from different biogeographical regions in Europe.

Rheological, Mechanical and Morphological Characterization of Fillers in the Nautical Field: The Role of Dispersing Agents on Composite Materials.

Coatings have a fundamental role in covering the external surface of yachts by acting both as protective and aesthetic layers. In particular, fillers represent the essential layer from the point of view of mechanical properties and consist of a polymeric matrix, different extenders and additives, and dispersing agents, with the latter having the role to provide good extender-matrix compatibility. In the present work, the effects of dispersing agents with an ionic or steric action on the interactions between hollow glass microspheres and an epoxy-polyamide resin are evaluated. Un-crosslinked filler materials are studied via rheological tests, whereas the mechanical and morphological properties of the crosslinked samples are assessed. The results clearly indicate that steric dispersing agents provide a much greater compatibility effect compared to ionic ones, owing to their steric hindrance capability, thus leading to better-performing filler materials with a less-marked Payne effect, which is here proved to be an efficient tool to provide information concerning the extent of component interactions in nautical fillers. To the best of our knowledge, this work represents the first attempt to deeply understand the role of dispersing agents, which are until now empirically used in the preparation of fillers.

A new flow-through bioassay for testing low-emission antifouling coatings.

Current antifouling (AF) technologies are based on the continuous release of biocides into the water, and consequently discharge into the environment. Major efforts to develop more environmentally friendly coatings require efficient testing in laboratory assays, followed by field studies. Barnacles are important fouling organisms worldwide, increasing hydrodynamic drag on ships and damaging coatings on underwater surfaces, and thus are extensively used as models in AF research, mostly in static, laboratory-based systems. Reliable flow-through test assays for the screening of biocide-containing AF paints, however, are rare. Herein, a flow-through bioassay was developed to screen for diverse low-release biocide paints, and to evaluate their effects on pre- and post-settlement traits in barnacles. The assay distinguishes between the effects from direct surface contact and bulk-water effects, which are crucial when developing low-emission AF coatings. This flow-through bioassay adds a new tool for rapid laboratory-based first-stage screening of candidate compounds and novel AF formulations.

Affinity states of biocides determine bioavailability and release rates in marine paints.

A challenge for the next generation marine antifouling (AF) paints is to deliver minimum amounts of biocides to the environment. The candidate AF compound medetomidine is here shown to be released at very low concentrations, ie ng ml(-1) day(-1). Moreover, the release rate of medetomidine differs substantially depending on the formulation of the paint, while inhibition of barnacle settlement is independent of release to the ambient water, ie the paint with the lowest release rate was the most effective in impeding barnacle colonisation. This highlights the critical role of chemical interactions between biocide, paint carrier and the solid/aqueous interface for release rate and AF performance. The results are discussed in the light of differential affinity states of the biocide, predicting AF activity in terms of a high surface affinity and preserved bioavailability. This may offer a general framework for the design of low-release paint systems using biocides for protection against biofouling on marine surfaces.

The impact of coating hardness on the anti-barnacle efficacy of an embedded antifouling biocide.

The efficacy of antifouling coatings designed to minimise the release of biocide, either by embedded (non-covalent) or tethered (covalently bonded) biocides, relies on sufficient bioavailability of the active compound upon contact between the organism and the coating. This investigation is focused on whether coating hardness affects the efficacy of embedded coating systems. Two experimental, non-eroding and waterborne latex paint formulations composed mainly of polystyrene (PS) or polyvinyl versatate (PV) were chosen for their difference in mechanical properties measured in terms of Buchholz indentation resistance. Ivermectin was added to both formulations to a final concentration of 0.1% (w/v) and the steady state release rate was measured according to ISO 15181 at between 34 and 70 ng cm(-2) day(-1) for both formulations. Field trials conducted over 3 months showed significant differences in anti-barnacle efficacy between the formulations despite their similar release profiles. The softer PV coating showed complete anti-barnacle efficacy, ie no barnacles were detected, while the harder PS coating showed no efficacy against barnacle colonisation during the same time period. The results indicate a new antifouling strategy whereby a route of intoxication is triggered by the organism itself upon interaction with the coating and its embedded biocide. This finding opens new possibilities in controlling macrofouling by low emission antifouling coatings.

Multi-seasonal barnacle (Balanus improvisus) protection achieved by trace amounts of a macrocyclic lactone (ivermectin) included in rosin-based coatings.

Rosin-based coatings loaded with 0.1% (w/v) ivermectin were found to be effective in preventing colonization by barnacles (Balanus improvisus) both on test panels as well as on yachts for at least two fouling seasons. The leaching rate of ivermectin was determined by mass-spectroscopy (LC/MS-MS) to be 0.7 ng cm(-2) day(-1). This low leaching rate, as deduced from the Higuchi model, is a result of the low loading, low water solubility, high affinity to the matrix and high molar volume of the model biocide. Comparison of ivermectin and control areas of panels immersed in the field showed undisturbed colonisation of barnacles after immersion for 35 days. After 73 days the mean barnacle base plate area on the controls was 13 mm(2), while on the ivermectin coating it was 3 mm(2). After 388 days, no barnacles were observed on the ivermectin coating while the barnacles on the control coating had reached a mean of 60 mm(2). In another series of coated panels, ivermectin was dissolved in a cosolvent mixture of propylene glycol and glycerol formal prior to the addition to the paint base. This method further improved the anti-barnacle performance of the coatings. An increased release rate (3 ng cm(-2) day(-1)) and dispersion of ivermectin, determined by fluorescence microscopy, and decreased hardness of the coatings were the consequences of the cosolvent mixture in the paint. The antifouling mechanism of macrocyclic lactones, such as avermectins, needs to be clarified in further studies. Beside chronic intoxication as ivermectin is slowly released from the paint film even contact intoxication occurring inside the coatings, triggered by penetration of the coating by barnacles, is a possible explanation for the mode of action and this is under investigation.

Fibrinogen adsorption and conformational change on model polymers: novel aspects of mutual molecular rearrangement.

By combining quartz crystal microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance (SPR), the organic mass, water content, and corresponding protein film structure of fibrinogen adsorbed to acrylic polymeric substrates with varying polymer chain flexibility was investigated. Albumin and immunoglobulin G were included as reference proteins. For fibrinogen, the QCM-D model resulted in decreased adsorbed mass with increased polymer chain flexibility. This stands in contrast to the SPR model, in which the adsorbed mass increased with increased polymer chain flexibility. As the QCM-D model includes the hydrodynamically coupled water, we propose that on the nonflexible polymer significant protein conformational change with water incorporation in the protein film takes place. Fibrinogen maintained a more native conformation on the flexible polymer, probably due to polymer chain rearrangement rather than protein conformational change. In comparison with immunoglobulin G and albumin, polymer chain flexibility had only minor impact on adsorbed mass and protein structure. Understanding the adsorption and corresponding conformational change of a protein together with the mutual rearrangement of the polymer chain upon adsorption not only has implications in biomaterial science but could also increase the efficacy of molecular imprinted polymers (MIPs).