Electrochemical and Redox Strategies for the Synthesis of Catecholamine- and Dihydroxynaphthalene-Based Materials: A Comparative Review

Abstract

Melanins are multifunctional biopolymers with unique properties, ranging from UV and radiation protection to antioxidant activity and metal chelation, making them highly attractive for biomedical applications. Despite extensive research, the mechanisms underlying melanin formation remain only partially understood, and access to these biopolymers therefore relies on suitable molecular precursors. While most studies have focused on catecholamine-derived eumelanins such as 3,4-dihydroxyphenylalanine (L-DOPA) and dihydroxyindole (DHI), nitrogen-free precursors such as 1,8-dihydroxynaphthalene (1,8-DHN) are emerging as promising routes to allomelanins. To date, however, these two precursor classes have largely been investigated separately, limiting a broader understanding of structure–function relationships. This review aims to compare electrochemical and redox-based pathways to catecholamine- and DHN-derived materials, emphasizing both their common principles and distinctive features. By bridging these parallel research streams, we propose a methodological framework for guiding future research on melanin-inspired materials and bioelectrochemical technologies.

1. Introduction

Biomimetic concepts provide a powerful framework for designing nanomaterials by emulating nature’s strategies: restricted set of chemicals, multifunctionality and hierarchical organization [1]. Natural materials and tissues often display self-healing behaviors due to the dynamic nature of the interactions ensuring their cohesion. The wings of morpho butterflies or the lotus leaves constitute some prototypal examples. The Dynates Hercules beetle highlights how structural organization and melanin pigments can combine to yield adaptative optical and protective function. This beetle features a multilayered chitin cuticle architecture, conferring it with structural coloration, while an underlying melanin layer ensures broadband light absorption. Under dry atmospheric conditions, the cuticle produces iridescence, but in humid environments, water penetrates in between the chitin layers which become nearly transparent, allowing light to be absorbed by the melanin and thus enabling humidity-dependent color adaptation [2].

Melanins are indeed a class of ubiquitous polyphenolic pigments synthesized by a wide variety of animals, plants and fungi and are known for their antioxidant, metal-chelating, and semiconducting properties [3]. Remarkably, their redox activity can switch between pro-oxidant and antioxidant behaviors depending on environmental conditions such as the presence of metal cation or oxidative stress levels, making them particularly interesting for bioinspired materials [4]. In addition, their composition seems to be extremely close to the insoluble organic matter found in many chondrite type meteorites [5,6].

From a historical perspective, the word “melanin” was introduced by Berzelius in 1840 to describe black animal pigments [7]. Structurally, melanins are traditionally divided into three groups: nitrogenous eumelanins, sulfur-containing pheomelanins and nitrogen-free allomelanins [8]. Pheomelanins, not of concern in this review, are red–brown compounds predominantly found in animals and produced by the reaction of the amino acid L-cysteine with the first oxidation product of catecholamines to yield benzothiazine and benzothiazole which undergo further oxidation and crosslinking steps [9].

Allomelanins are nitrogen-free black pigments primarily found in fungi and obtained through the polyketide synthase pathway using DHNs as precursors [10,11].

In plants, polyphenols associated with transition metal cations are the major building blocks of melanins. Polyphenols are a class of molecules containing several phenols or hydroxylated phenols [12]. Such molecules are now intensively used as crosslinking agents [13,14] and adhesion promotors [15].

All types of eumelanins and allomelanins exhibit, to varying extents, a dark coloration that plays a role in photo and radioprotection [16,17]. The exact origin of this black chromophore remains unclear but is suspected to arise from a high degree of chemical disorder [18]. This dark coloration also explains their very low fluorescence quantum yield [19].

Interestingly, melanins are paramagnetic materials in direct relation with the redox reactions at their origin, leading to the formation of a fraction of semiquinone groups [20].

The actual incomplete knowledge about the formation mechanism of melanins can be found in other reviews [17] and will not be discussed in this article.

While most studies have focused on catecholamine-derived eumelanins such as L-DOPA, dopamine or 5,6-DHI, 1,8-DHN has emerged as a promising precursor for its deep black coloration and antioxidant properties.

Despite decades of research, melanin formation pathways remain only partially understood, limiting control over their synthesis. In this context, electrochemical methods offer unique advantages as they confine oxidation and polymerization to electrode surfaces, preventing monomer loss through precipitation, and enabling the direct deposition of functional melanin-based films on conductive substrates.

In this review, we aim to compare electrochemical and redox pathways to catecholamine- and DHN-based nanomaterials and films, with a particular emphasis on both shared principles and specificities (Figure 1).

Overall, this review article aimed to compare knowledge acquired in the field of catecholamine and DHN chemistry, with a common topic relying on the central, but not unique, role played by redox chemistry. The main aim was to illustrate the fact that all the methods employed are robust and easy to implement, explaining the success of this field in applied surface and in colloid science, but with a severe lack of fundamental knowledge in the reaction pathways underlying the formation of such materials. This gap between already developed (perhaps not optimized) materials and their fundamental knowledge lies probably in the materials’ heterogeneity and the absence of truly adapted characterization methods. It is an enormous challenge to investigate such research topics because they allow for investigating real natural materials with a kind of biomimetic approach, as already mentioned, but also to leave beaten tracks which allow for progress with confidence in the field of crystalline solids or polymeric materials. In catecholamine and DHN chemistry, only reasonable models [7,21] can be proposed, and it is our assumption that the comparison between both kinds of materials, identifying analogies and differences, may help to progress in their understanding.

Focus will be on electrochemical deposition, in addition to redox chemistry in solution, as a powerful strategy to form melanin-inspired films with tailored properties. We will hence expand the scope of previous reviews [21]. This work is organized into three sections: particles formation in solution, films obtained from precursors in solution and electrochemical deposition and characterization of melanin-based materials.

2. Solution Chemistry of Catecholamines and DHN for Material Engineering

2.1. Precipitates and Spherical Nanoparticles

The oxidation of dopamine and other catecholamines (as well as polyphenols) in solution allows for the production of insoluble and a priori useless precipitates. But various templating methods or the use of radical species enable the production of nanoparticles of controlled size and good colloidal stability [22]. Such aspects of controlled polydopamine (PDA) nanoparticles synthesis have already been reviewed [23]. It may not be excluded that the additives used during PDA synthesis provide some colloidal stabilization to the fundamental building blocks of eumelanin-like materials. Indeed, eumelanin from Sepia officinalis appears as a hierarchical material made from spherical aggregates of about 150–200 nm in diameter which seem to be constituted of smaller spherical nanoparticles [24].

The possibility to control the self-assembly of polydopamine to yield nanoparticles in the few nanometer range by oxidizing dopamine in the presence of proteins is of particular interest [25,26,27,28]. Short tripeptides containing tyrosine as a common amino acid also self-assemble in a sequence-specific manner under oxidative conditions [29]. These investigations, aiming to control the size and shape of eumelanin-like colloids, are intrinsically of biomimetic nature: natural eumelanins are almost always surrounded by protein shells, which also holds true for allomelanins [30]. In addition, boric acid can prevent the self-assembly of polydopamine by forming strong hydrogen bonds with adjacent hydroxyl groups that considerably hinder its further oxidation and allow for the control of particle size (at high boric acid/dopamine ratio) following a fixed oxidation time [31]. For instance, after an addition of a 20-fold excess of boric acid with respect to the initial concentration of dopamine, the size of the PDA particles is limited to 650 ± 50 nm after three hours of oxidation, whereas the particle size can exceed 1600 nm in the absence of boric acid, ultimately leading to precipitation [31].

DHNs can also undergo self-assembly or polymerization in oxidative conditions. Upon oxidation, using peroxidase or laccase as a catalyst, tandem mass spectrometry made it possible to show that 1,8-DHN dimers are linked through carbon–carbon bonds and not via ether bonds (namely C-O-C). However, the oxidation of 2,7-DHN yields C-O interring coupling [32].

On this basis, allomelanin nanoparticles were synthesized through the oxidation of 1,8-DHN in the presence of three oxidants: sodium periodate (NaIO₄), potassium permanganate (KMnO₄) and O₂ (the reaction being catalyzed by laccase). With NaIO₄, increasing the oxidant/1,8-DHN ratio reduced nanoparticle sphericity (as shown by transmission electron microscopy (TEM) and dynamic light scattering (DLS)) while enhancing oligomerization, evidenced by electrospray mass spectrometry after nanoparticle dissolution in acetonitrile [33]. The 1,8-DHN nanoparticles displayed higher antioxidant activity (measured by the discoloration of 2,2-diphenyl-1-picrylhydrazyl (DPPH)) per mass unit than PDA nanoparticles, and similar activity to ascorbic acid. This higher antioxidant activity has been confirmed by others [34].

Also, unlike PDA, the solid-state ¹³C nuclear magnetic resonance (NMR) spectra of allomelanins revealed the absence of aliphatic carbons, showing the integrity of the aromatic cycles during oxidation [33]. Finally, the allomelanin nanoparticles were internalized by neonatal human epidermal keratinocytes and displayed a strong reduction in the generation of reactive oxygen species upon irradiation [33].

In a similar investigation, 1,8-DHN-based nanoparticles were synthesized using hydrogen peroxide (H₂O₂) as the oxidant and peroxidase as a catalyst [35]. Their electron paramagnetic resonance spectra were investigated in the solid state and after redispersion of the particles in different ionic liquids. In the solid state, the g factor amounted to 2.0030, with a linewidth of 4.8 G, typical of carbon-localized free radicals. Signal broadening increased in the presence of ionic liquids, particularly those with low polarity and a strong hydrogen bond acceptor basicity [35]. It was concluded that the disassembly of allomelanin by ionic liquids, yielding the distribution of oligomers and inducing spin delocalization. As in the investigation published by Zhou et al. [33], the allomelanin particles displayed a higher antioxidant activity per mass unit than PDA nanomaterial made from L-DOPA. A similar electron paramagnetic resonance (EPR)-based investigation was performed on PDA. Similarly to DHN-based allomelanins, ionic liquids induced a disassembly of PDA (in this case, a PDA film dissolution and redispersion in the form of nanoparticles) but with a difference: a partial conversion of C-centered radicals to O-centered semiquinone radicals [36].

The obtained microstructures were also submitted to ammonia-induced solid-state polymerization [37], with the consequence of obtaining rigid particles with an important loss of crystallinity [38].

A very interesting study aimed to determine whether the degree of black coloration in a group of synthetic allomelanins derived from DHN isomers could be described as an emergent property related to redox disorder and thus considered an index of π-electron complexity. Among the molecules tested, 1,6-DHN and 1,8-DHN displayed a higher degree of polymerization (after oxidation) and electron spin density compared to other isomers, along with a darker coloration. The materials produced from these molecules also displayed higher spin densities (around 9 × 10¹⁸ g⁻¹) than DHI-based eumelanin even if their EPR spectra are very similar (Figure 2). These findings suggest that “blackness” is linked to high electron spin density and degree of polymerization, indicative of a higher oxidation state, and can, therefore, be seen as a primary indicator of π-electron complexity [39]. Unfortunately, but justified in the original article [39], some commercially available isomers of DHN, like 1,3-DHN, 1,5-DHN, 1,7-DHN and 2,3-DHN, have not been investigated. This could constitute an interesting perspective to get a better understanding of the redox properties of the DHN isomers in relation to their structure.

A common feature of catecholamine-based eumelanins and DHN-based allomelanins is the presence of small oligomers rather than high molecular weight polymers as evidenced by matrix assisted laser desorption–time of flight mass spectrometry [39,40]. Sepia officinalis-based eumelanins are rich in dihydroxyindole-2-carboxylic acid trimers, tetramers and pentamers [40], whereas 1,8-DHN-based allomelanins contain up to decamers [39].

Transient absorption spectroscopy and EPR spectroscopy enabled the investigation of the relaxation dynamics of 1,8-DHN-based nanoparticles produced by NaIO₄ oxidation after light absorption [41]. Following femtosecond irradiation, the material underwent rapid wavelength-dependent relaxation (hundreds of fs), followed by a much slower process (hundreds of µs) accompanied by increased EPR absorption and semiquinone radical formation. Irradiation also enhanced antioxidant activity, as shown by greater quenching of the DPPH radical [41].

2.2. Anisotropic Nanomaterials

Beyond obtaining spherical nanoparticles, efforts have been made to obtain anisotropic nanomaterials from both catecholamines and DHNs. In particular, the oxidation of dopamine in the presence of folic acid, able to form anisotropic hydrogen-bonded networks (Figure 3(Aa)), allows for the formation of PDA nanofibers (Figure 3(Ad,Ae)) [42,43]. The investigation of the role of other anisotropic molecules able to form hydrogen bonds with oxidized dopamine oligomers should be extended to get other kinds of morphologies for the obtained PDA.

Concerning the possibility of getting anisotropic nanomaterials from DHNs, the 2,2′, 2,4′ and 4,4′ isomers were synthesized, dissolved in acetonitrile and self-assembled upon dialysis against ultrapure water for two days. The 2,2′ and 2,4′ isomers yielded spherical particles in the few hundred nanometer diameter range (Figure 3(Ba,Bc,Bd)). However, the 4,4′ dimer self-assembled in crystalline platelets of 5 to 10 µm in length and 1 to 2 µm in thickness (Figure 3(Ba,Bb)). The self-assembly process was performed by either slow or fast water addition to the acetonitrile solution of the 4,4′ dimer, yielding, respectively, ordered or disordered ellipsoidal particles with an identical crystal structure [38]. The change in material morphology as a function of the water addition rate was rationalized by considering the location of water molecules within the crystal structure. Specifically, water forms hydrogen bonds between adjacent layers of the self-assembled 4,4′-DHN dimers along the [100] direction. The platelet shape of the 4,4′ dimer-based crystal is also directly related to a high dihedral angle (108°) between the two naphthalene rings. Consequently, the hydroxyl groups are oriented in opposite directions which is favorable for an anisotropic self-assembly process. Note that the self-assembly of the DHN dimers was performed in the absence of oxidizing conditions. The obtained nanostructures are hence only due to non-covalent interactions. Even if such materials are not obtained via redox chemistry, they display potentially redox properties. These include antioxidant activities, the possibility to induce metallic cation reduction and hence post-functionalization with nanoparticles. These properties may also depend on particle shape and porosity.

2.3. Porosity Control

Concerning DHN-based colloids, MacCallum et al. [44] demonstrated that porous allomelanin nanoparticles (AMNPs) in the 100 nm size range can be synthesized through the oxidative polymerization of 1,8-DHN (Figure 4A).

Depending on the aging process after a 24 h NaIO₄ oxidation (in a water/acetonitrile mixture) and methanol etching, three distinct types of AMNPs could be produced. Spherical allomelanin nanoparticles (S-AMNPs), characterized by a smooth surface and uniform density, were obtained via the spontaneous self-assembly of allomelanin dimers, trimers and oligomers in solution (Figure 4(Aa–Ae)). After 24 h, these S-AMNPs could be etched with methanol (MeOH) to produce hollow nanoparticles (H-AMNPs, Figure 4(Af–Aj)) composed of a hollow core surrounded by a dense shell. Further aging and MeOH etching yielded lacey nanoparticles (L-AMNPs, Figure 4(Ak–Ao)), characterized by a higher surface area and more intricate internal architecture.

DLS measurements revealed hydrodynamic diameters of 154 nm for S-AMNPs, 184 nm for H-AMNPs, and 150 nm for L-AMNPs.

The porosity of the nanoparticles was assessed via nitrogen physisorption at 77 K. Two main pore sizes, approximately 6 Å and 12 Å, were observed across all AMNP types but L-AMNPs had a significantly higher pore volume (0.6 cm³/g) compared to S- and H-AMNPs (both around 0.35 cm³/g). The transition from S-AMNPs to H-AMNPs, and finally to L-AMNPs has been explained by the interpretation of small-angle X-ray scattering data: the dissolution of the particles in the core leaves some porosity, and the leached material redeposits on the shell of the particles [44].

This porosity, combined with the presence of surface hydroxyl groups, suggests a strong potential for ammonia capture and storage. Indeed, ammonia adsorption isotherms at 298 K evidenced strong interaction between NH₃ and AMNPs, making them promising candidates for air filtration applications.

AMNPs also exhibited carbon dioxide/methane (CO₂/CH₄) selectivity comparable to that of metal–organic frameworks (MOFs), highlighting their potential for CO₂ separation from natural gas [44].

In addition, the nanoparticles demonstrated toxin adsorption capabilities toward diazinon and paraoxon (Figure 4B), two common pesticides used as analogs for warfare nerve agents.

To evaluate their protective potential, porous AMNPs were applied as coatings on nylon–cotton (NYCO) fabric and tested for their ability to inhibit the permeation of dimethyl methylphosphonate (DMMP), a sarin gas simulant. Fabrics coated with H-AMNPs and L-AMNPs showed significantly better performance compared to those treated with S-AMNPs, 1,8-DHN monomers, or untreated controls. Importantly, these coatings did not impede water vapor transmission, suggesting that comfort of the fabric was not altered. This ability to block DMMP transport positions AMNPs as promising candidates for use as functional dyes in protective uniforms [44].

Finally, AMNPs were compared to allomelanin ghost microstructures derived from fungal cells that naturally produce DHN. These melanized hollow shells were found to be relatively non-porous compared to AMNPs. However, they surprisingly exhibited better adsorption of both diazinon and paraoxon than S- and L-AMNPs, though not as effective as H-AMNPs [44].

All these findings highlight the versatility and functional potential of artificial allomelanin nanoparticles. By tuning their morphology and porosity through controlled aging and methanol etching, it is possible to produce nanostructures with tailored properties for specific applications. The hollow and lacey variants show, for example, strong promise for use in air filtration, gas separation, and protective coatings [44].

Allomelanin particles can hence be made porous through a single change in solvent. This does not seem to be the case for PDA and other catecholamine-based particles. Indeed, PDA nanoparticles have been prepared using NaIO₄ as the oxidant [23], but the influence of prolonged incubation in ethanol on their porosity has not been investigated to our knowledge. To make such materials porous, templating methods are required. The PDA of varying thickness is deposited on a sacrificial template, which is subsequently dissolved in an appropriate solvent; making it a complex process requiring many centrifugational purification steps to remove the core dissolving solvent [45,46]. The reasons why DHN-based materials obtained via oxidation are more porous and less stable upon a change in solvent than their catecholamines counterparts remain to be investigated. At this stage, we make the assumption that DHN-based oligomers are more crowded than catecholamine-based materials, which can potentially form linear oligomers [3].

To our knowledge, no attempts were made to investigate the influence of surfactants, proteins or other templating agents on the formation of DHN-based materials.

3. Solution Oxidation for Film Formation from Catecholamines and DHNs

3.1. Deposition from Solution Under Oxidizing Conditions

Catecholamine-based films can be deposited on almost all known substrates, including metals, oxides, and polymers from a catecholamine containing solution in the presence of an oxidant. The first and most frequently used oxidant is the oxygen naturally dissolved in water [47]. Polydopamine films are constituted by a mixture of polymeric species, probably of low molecular weight as in melanins, and by self-assembled subunits such as (dopamine)₂-DHI [48]. π–π [49] and cation–π interactions play an important role in stabilizing the structure of the resulting films or particles [50].

Such melanin-like coatings can be obtained from a vast repertoire of catecholamines, including dopamine [47], norepinephrine [51] and L-DOPA [52]. The final thickness of the coatings, their chemical composition and their properties depend on the nature of the catecholamine and the used oxidant [53,54,55], but also on the nature of the substrate [56] in a subtle and yet not completely understood manner. The standard redox potential of the used oxidant plays a major role in the oxidation of dopamine, in the kinetics of film deposition and in the structure of the obtained films: among the investigated oxidants, NaIO₄ and CuSO₄ + H₂O₂ allow for getting the thickest coatings. These strong oxidants not only speed up the oxidation of dopamine and the subsequent deposition process [54,55] but also induce a significant increase in the O/C ratio in the films (as determined by X-ray photoelectron spectroscopy), meaning increased oxidation of the film with the occurrence of some possible muconic cleavages [55]. Noteworthy, the strongest investigated oxidant, ammonium persulfate (E° = 2.12 V vs. the normal hydrogen electrode) was less efficient in the PDA film deposition than NaIO₄. This was explained by the fact that persulfate has to undergo decomposition in hydrogenosulfate which acts as the effective oxidant [55]. Hence, the oxidation of dopamine is kinetically limited in these conditions.

Of particular interest is the possibility to form similar films from either pure dopamine solutions [57,58] or from dopamine–polymer blends [59,60] at the water–air interface (using different kinds of oxidants) but in the absence of solution agitation. Indeed, strong shear forces are sufficient to break the self-assembled nanostructures at the water–air interface. To our knowledge, the film deposition at the water–air interface from 1,8-DHN solutions has not yet been investigated or reported.

However, not all catecholamines enable film deposition under oxidizing conditions: 5,6-DHI, the final oxidation product of dopamine before its oligomerization, oxidizes spontaneously and rapidly but without film formation [61]. This important result suggests that the early steps of dopamine oxidation play an important role in the deposition of PDA.

When dopamine is modified with electron-withdrawing groups on its aromatic cycle, like nitro groups, the film formation is almost completely inhibited [62].

Even if intensive research efforts have been devoted to the reaction mechanism leading to PDA and other catecholamine-related films and materials, many details remain unknown due to the difficulty of a full characterization of such amorphous and insoluble materials [63,64].

The application fields of those catecholamine-based versatile coatings have been widely reviewed [17,47] and are not the scope of this article.

In sharp contrast to catecholamines, when catechols and small polyphenols are exposed to sufficiently strong oxidants in the presence of substrates, the catechol undergoes oxidation in solution as expected from thermodynamic considerations, leading to precipitation or nanoparticles formation rather than film deposition. However, this ability to form films can be restored by adding a diamine like hexamethylenediamine (HMDA) to the catechol containing solution. Prototypal examples concern film formation from gallic acid [65], pyrocatechol [66] and caffeic acid [67] solutions in the presence of HMDA. As a control, when HMDA is acetylated, no film formation is found in the presence of oxygen at pH 9 [68]. In this context, DHNs also undergo solution oxidation to yield nanomaterials, but do not form any coatings on the walls of the reaction beaker or on immersed substrates. It may be of interest to investigate the possibility to deposit 1,8-DHN based films in the presence of HMDA and other diamines with variable spacers. One may anticipate that the quinones obtained during the oxidation process will undergo nucleophilic addition or Schiff base formation by one of the amino groups from the diamine, the other nucleophilic center remaining available for addition on a neighboring oxidized DHN, ensuring crosslinking [13] and subsequent film deposition.

Interestingly, multifunctional coatings can be obtained in the presence of an appropriate oxidant and blends of polyphenols and catecholamines [69]. In some cases, the two components acted in a synergistic manner, to yield thicker coatings than catecholamines alone, but in other instances, they acted antagonistically [69]. Much more research is clearly required to build up films from catecholamine–catechol blends.

The oxidation of 1,8-DHN in the presence of solid surfaces does not lead to film deposition in a way similar to catechol and other derivatives of phenol but in marked contrast with most of the investigated catecholamines. To our knowledge, DHNs blended with diamines have not yet been explored for their film forming ability. This constitutes an important perspective in this research field.

As a marked counterexample, large and hydrolysable polyphenols like tannic acid form spontaneously nanometer thick coatings on almost all kinds of materials in absence of any oxidation process [70]. This probably originates from a positive cooperation between a large number of small gallic acid moieties which individually display only weak adsorption affinity on surfaces.

3.2. Coordination-Driven Self-Assembly with Polyphenols

Coordination-driven (with Fe³⁺ and Cu²⁺) self-assembly with polyphenols constitutes a versatile surface functionalization method [71]. It allows for the synthesis of hollow capsules after dissolution of the template on which the coordination driven self-assembly was performed [72]. In such deposition processes redox chemistry, namely partial reduction of the metallic cations and partial oxidation of the polyphenols compete and complement with coordination-driven mechanisms. The direct incorporation of metallic cations in the coatings will enlarge their application fields with respect to purely polyphenol-based coatings, particularly for antimicrobial properties.

To our knowledge, DHNs have not yet been used in combination with transition metal cations to yield conformal coatings. Investigations in this direction should be performed because of the potential coordination chemistry of DHNs, particularly the DHNs with vicinal hydroxyl groups.

3.3. Ammonia-Induced Solid-State Polymerization Deposition

Ammonia-induced solid-state polymerization (AISSP) deposition has been shown to be successful for DHI [73] and 1,8-DHN [37], contrarily to oxidative deposition from solution (Section 3.1), which was inefficient for both compounds. AISSP consists of spin-coating a solution of the target molecule, drying the resulting film and exposing it to an ammonia flow (as a catalyst) in the presence of air as the oxidant (Figure 5). Unlike dopamine oxidation, this process yields coatings without monomer loss. The final coating thickness is dictated by the characteristics of the initial spin-coated precursor film.

Nylon membranes coated with 1,8-DHN allomelanin using the AISSP deposition were used for the elimination of the toxic methylene blue dye both in batch and in-flow conditions. The maximal adsorption capacity of the 1,8-DHN-based film was 262 mg/g, in probable relation to the porous nature of the coating [74]. This AISSP produced allomelanin coating did not show delamination from the nylon support and could be regenerated up to seven times in methylene blue adsorption–desorption cycles without loss in removal efficiency [74].

4. Electrochemistry of Catecholamines and DHNs

4.1. Deposition by Cyclic Voltammetry (CV) or Chronoamperometry (CA)

The passivation of electrodes used for sensing-specific solutes in the presence of phenols and polyphenols has been established for a long time [75] and constitutes a major drawback for such applications. However, if the electrodeposition is carried out on purpose from solutions of pure catecholamines or polyphenols, it constitutes an efficient functionalization method by allowing for the deposition of conformal films without the loss of building blocks due to precipitation in solution. Indeed, in electrochemical deposition, the oxidation process and upcoming chemical mechanisms are restricted at the electrode or film surface.

Since then, numerous studies have focused on the electrochemical deposition of eumelanin precursors, mostly dopamine (Figure 6A) [76,77,78,79,80,81], but also polyphenols [82,83] for which significant insights into the deposition mechanism are known [84,85].

The electropolymerized films obtained from either catecholamines or polyphenols are usually very thin (nanometers to tens of nanometers), with one noticeable exception: the films obtained through the CV deposition of 3-amino-L-tyrosine (Figure 6B,D) [86].

Interestingly, the CV deposition of dopamine was compared to that of L-DOPA, 5-hydroxytryptophan (5-HTP) and adrenaline on indium–tin oxide and gold working electrodes in deoxygenated 25 mM Tris buffer at pH 7.4. The thickness and the stability (tested through up to 1000 CV cycles in the presence of potassium hexacyanoferrate) of the PDA-based films were found to be higher than those based on L-DOPA and 5-HTP. CV performed with adrenaline did not result in any film formation. This finding was related to the presence of a secondary amine in this later compound whereas the other investigated catecholamines contained a primary amino group, able to easily undergo a nucleophilic addition on the quinone groups obtained through electrochemical oxidation [79].

The PDA films obtained through CV (in deoxygenated Tris buffer at pH = 8.5) were compared to films deposited from dopamine solutions in the presence of dissolved oxygen at the same pH: the former were found to be permeable to hexacyanoferrate anions up to a film thickness of 30 nm above which they suddenly became impermeable, whereas the latter reached an impermeable state at a much lower thickness of 5–10 nm [77]. The permeability of all this PDA-based films is higher for the positively charged hexaamineruthenium (II) than for the negatively charged hexacyanoferrate owing to their negative charge at the pH of the experiment. Overall, these observations can be explained by the pH-dependent charge of PDA (its isoelectric point is close to 4.5 [87]) and the resulting Donnan potential of the films, but also by a difference in their porosity, which remains to be quantified.

Catecholamines and 1,8-DHN display markedly different behaviors when the CVs are performed at different potential sweep rates. The deposition of dopamine-based films on electrodes is totally inhibited when the potential sweep rate is higher than 10–20 mV.s⁻¹ whereas the deposition of 1,8-DHN-based films can be performed up to 1000 mV.s⁻¹ even if the deposition rate (and the resulting film thickness after a given number of CV cycles) decreases with the potential sweep rate [88]. Indeed, the CVs of dopamine at high potential sweep rate display an almost reversible character, meaning identical oxidation peak and reduction peak currents. This can be explained by the fact that fully oxidized dopamine, namely dopaminequinone, can undergo intramolecular cyclization through the unprotonated amino group (absent in 1,8-DHN) only if the lifetime of this oxidation product is long enough. When its reduction is faster than the nucleophilic addition (and hence cyclization), reversible redox behavior but no subsequent non-electrochemical pathways will be observed [89].

CV experiments performed at different pH values in dopamine solutions suggest that the oxidation process involves two electrons and the concomitant loss of two protons, hence an electron–proton-coupled mechanism [76,78]. However, the formation of semi-quinones during the oxidation process may also play an important role as exemplified for similar materials produced by oxidation in solution [36]. No such experiments, performed at different pH values, have been performed up to now with 1,8-DHN and constitute an imperative research goal.

Dopamine has also been electropolymerized with pyrrole [90] to yield electrically conductive films, a specific property of polypyrrole but not of polydopamine.

The cyclic voltametric oxidation of 1- and 2-naphtol on platinum working electrodes induces electrode passivation in a solvent-dependent manner, with only minimal electrode passivation observed in acetonitrile [91].

Up to very recently, functional electrodeposited films of 1,8-DHN had not been explored. Such films were deposited from a 1 g.L⁻¹ solution of 1,8-DHN in a 50/50 mixture of sodium acetate buffer (50 mM) and ethanol (70%), using CV on gold-coated slides at scan rates of 20, 200, and 1000 mV/s (Figure 6C) [88]. CA was also used to get films from 1,8-DHN solutions.

Surprisingly, the resulting coatings were thick (several hundred nanometers after 25 CV cycles and up to 1.3 µm after 100 CV cycles with a potential sweep rate of 20 mV.s⁻¹, Figure 6E), despite the material’s insulating behavior suggested by electrochemical impedance spectroscopy. Nevertheless, the films were semipermeable to two redox probes (hexaammineruthenium (III) chloride and potassium hexacyanoferrate), indicating a certain level of porosity as in the case of PDA electrodeposited films [77].

Contact angle measurements revealed a hydrophilic nature across all scan rates, and the films remained stable in aqueous environments for at least 15 days. Raman, infra-red and X-ray photoelectron spectroscopy analysis suggested that the monomers were assembled by both covalent C–C bonds and non-covalent interactions, likely involving hydrogen bonding between unoxidized -OH groups and π–π interactions. However, these techniques did not allow for the determination of the polymerization degree, which has been shown to reach 21 when 1,8-DHN is oxidized in solution [39].

CV curves of the deposited films showed a broad oxidation peak, indicating an electroactive behavior with some possible applications as supercapacitors. Additionally, the DPPH assay confirmed strong antioxidant activity, which appeared to increase almost proportionally with the film thickness, in agreement with an important porosity (remaining to be quantified). In addition, the coatings inhibited the growth of two Pseudomonas aeruginosa strains in comparison to pristine gold electrodes, suggesting antibacterial properties which yet need to be confirmed with other bacterial strains.

Finally, 1,8-DHN-based films electrodeposited at 200 mV.s⁻¹ could be detached from the electrode surface and exhibited an elastic modulus of approximately 700 MPa, as measured by Strain Induced Elastomer Buckling Instability for Mechanical Measurements (SIEBIMM) [88]. Combined with their other functional properties, this mechanical resilience points to potential applications as filtration membranes (as in [74] for AISSP produced films) and tissue engineering. It should be noted that very thin electropolymerized PDA films (tens of nanometers in thickness) can also be easily detached from their supporting electrode using the same lift-off technique applied to 1,8-DHN-based films [80]. These findings point to an interesting common feature between PDA and 1,8-DHN-based electrodeposited films: both exhibit a high mechanical toughness and could be used as filtration membranes.

In conclusion, the electrodeposition of 1,8-DHN onto gold electrodes yields thick, insulating, yet electroactive, porous films that demonstrate strong antioxidant and antibacterial properties with the benefit of being produced under green chemistry conditions. To our knowledge, aside from conductive polymers, only one similar example has been reported in the literature, describing an increase in the oxidation–reduction current with the number of potential sweep cycles, finally leading to thick coatings: the electrodeposition of 1,2-dihydroxybenzene on platinum electrodes in boron trifluoride diethyl etherate [84]. In this case, the resulting film displayed an electrical conductivity of 9.16 × 10⁻⁴ S.cm⁻¹ at 292.4 K. Contrarily to the electrodeposited film from 1,8-DHN, the electrodeposited material obtained from 1,2-dihydroxybenzene could be solubilized in the de-doped state and in polar solvents (dimethylsulfoxide, tetrahydrofuran and ammonia). This allowed for its characterization by solution state ¹H and ¹³C-NMR spectroscopies [84], which showed that the branching occurred in positions 4 and 5 of the benzene ring. When 1,2-dihydroxybenzene is deposited by CV (at a 20 mV.s⁻¹ potential sweep rate) on amorphous carbon electrodes in the presence of 50 mM sodium acetate buffer, some crystalline domains appeared in the films with lattice spacings close to graphene oxide [92].

Figure 6. (A) Successive CVs of dopamine on a glassy carbon electrode at pH 7.0. The arrows indicate the current evolution upon increasing the number of CV cycles. Reproduced from [78] with authorization from Wiley Interscience. (B) Successive CVs (at a potential sweep rate of 10 mV.s⁻¹) of 3-amino-L-tyrosine on gold coated glass slides in the presence of 100 mM phosphate buffer at pH = 7.0. Reproduced from [86] with authorization from Wiley VCH. (C) CVs of 1,8-DHN (1 mg.mL⁻¹ in the presence of sodium acetate 50 mM + 70% ethanol (1:1 v/v)) on gold electrodes at three different potential sweep rates: 20, 200 and 1000 mV.s⁻¹. The full lines represent the first CV cycle whereas the dashed lines represent the 5th CV cycle. The arrow indicates the evolution of the CVs when the potential sweep rate is increased. Reproduced from [88] with authorization from the American Chemical Society. (D) Mass changes as recorded by electrochemical quartz microbalance during the deposition by CV of dopamine (grey line), norepinephrine (blue line) and 3-amino-L-tyrosine (orange line). Reproduced from [86] with authorization from Wiley VCH. (E) Thickness of 1,8-DHN based films obtained by CV as a function of the number of CV cycles after 25 (orange symbols and line) and after 100 CV cycles (purple symbols and line). Reproduced from [88] with authorization from the American Chemical Society.

Figure 6. (A) Successive CVs of dopamine on a glassy carbon electrode at pH 7.0. The arrows indicate the current evolution upon increasing the number of CV cycles. Reproduced from [78] with authorization from Wiley Interscience. (B) Successive CVs (at a potential sweep rate of 10 mV.s⁻¹) of 3-amino-L-tyrosine on gold coated glass slides in the presence of 100 mM phosphate buffer at pH = 7.0. Reproduced from [86] with authorization from Wiley VCH. (C) CVs of 1,8-DHN (1 mg.mL⁻¹ in the presence of sodium acetate 50 mM + 70% ethanol (1:1 v/v)) on gold electrodes at three different potential sweep rates: 20, 200 and 1000 mV.s⁻¹. The full lines represent the first CV cycle whereas the dashed lines represent the 5th CV cycle. The arrow indicates the evolution of the CVs when the potential sweep rate is increased. Reproduced from [88] with authorization from the American Chemical Society. (D) Mass changes as recorded by electrochemical quartz microbalance during the deposition by CV of dopamine (grey line), norepinephrine (blue line) and 3-amino-L-tyrosine (orange line). Reproduced from [86] with authorization from Wiley VCH. (E) Thickness of 1,8-DHN based films obtained by CV as a function of the number of CV cycles after 25 (orange symbols and line) and after 100 CV cycles (purple symbols and line). Reproduced from [88] with authorization from the American Chemical Society.

Very thick films can be obtained from the CV deposition of pyrrole [93,94], aniline and thiophene owing to their conductive behavior. The question then arises if the very thick allomelanin films obtained by CV and by CA are the result of their intrinsic electrical conductivity or to their porosity. This property, already evidenced for allomelanin nanoparticles [44], may enable the diffusion of 1,8-DHN monomers from the solution close to the electrode surface where oxidation, further polymerization and self-assembly may occur. The deposited film would then swell and allow for further film deposition. Such a hypothetical mechanism needs, of course, to be validated on an experimental basis, using for instance electrochemical quartz crystal microbalance. Such an intrinsic porosity of electrodeposited 1,8-DHN-based films may be exploited in real world technologies for water filtration purposes. Indeed, the DHN films could be electrodeposited on porous metallic meshes providing some functionality in terms of pollutant retention without reducing the water flux across the designed filtration grid.

Surprisingly, among the possible DHN isomers, only 1,8-DHN has been tested for the possibility to produce films via electrodeposition. Hence, a huge effort should be dedicated to comparing the different DHN isomers. In the case of catecholamine, comparative studies have already been performed between closely related molecules [79] and it appeared that dopamine and 3-amino-L-tyrosine [86] are the best candidates for conformal film deposition by CV. It has to be noted, however, that electrodeposited films from 2,6-dihydroxynaphthalene have been shown to be efficient sensing platforms for peroxynitrite [95]. The numerous sensing possibilities of electrodeposited PDA materials have already been reviewed [81] and will, therefore, not be discussed here.

4.2. Electrochemical Tools to Investigate Melanins’ Redox Properties

From a totally different approach, sepia (obtained from the oxidation of 5,6-dihydroxyindole-2-carboxylic acid) and fungal melanin (probably based on 1,8-DHN) were integrated in electrode deposited hydrogels to probe their ability to give electrons or to retrieve them after diffusion of redox mediators in the composite material. The dual redox activity of those melanins was related to their antioxidant or pro-oxidant activities [96,97,98]. The incorporation of melanins in hydrogels allowing for the diffusion of redox mediators enables the mimicry of the indirect electron transfer processes occurring in biological systems. The simultaneous incorporation of graphene and black soldier fly melanin in these hydrogels made it possible to mimic direct electron transfer processes in the sense that graphene served to “wire” the electrode surface with the melanin particles [99]. Such investigations using hydrogel immobilized eumelanins or allomelanins may offer interesting perspectives for energy storage applications. Indeed, many experimental data showed the possibility to use melanins as supercapacitors owing to their intrinsic dual electron acceptor–electron donor ability [100,101].

5. Discussion and Conclusions

Catecholamines, polyphenols and DHNs are biomolecules enabling the straightforward and eco-friendly synthesis of nanomaterials and films. Among the latter category of materials, the films can be produced either via the electrochemical deposition or AISSP. Besides this common behavior, catecholamine- and DHN-based materials differ by several points:

(i)

Catecholamine-based eumelanins have been much more investigated than DHN-based allomelanins, since research interest on the latter has arisen only within the past decade.

(ii)

DHNs, like most of the polyphenols (tannic acid being a noticeable exception [70]), cannot be deposited directly from solution whereas most of the catecholamines (DHI being an exception [61]) allow for film formation on the surface of almost all known materials in the presence of a strong enough oxidant.

(iii)

Concerning the synthesis of nanomaterials, DHNs seem to offer a much greater versatility than catecholamines. Except at very low precursor concentrations, the solution oxidation of catecholamines (and of catechols) induces precipitates. To obtain nanomaterials from catecholamines and catechols, templating agents such as proteins or boric acid, must be added at sufficiently high molar ratios. In contrast, the oxidation of 1,8-DHN leads to nanoparticles in a one-step process [44]. In addition, the porosity of the 1,8-DHN nanoparticles can be easily tailored post-synthetically by solvent treatment with methanol. On the other hand, obtaining porous capsules from PDA is much more complex for it requires PDA deposition on a sacrificial template followed by dissolution of the core with an appropriate solvent [45,46].

(iv)

Regarding film electrodeposition, which requires a conductive substrate, extensive data exists for catecholamines and catechols. Among DHN isomers, to our knowledge, only 1,8-DHN [88] and 2,6-DHN [95] have been investigated. For 1,8-DHN, it was shown that the intrinsic limitation of catecholamine–catechol-based films, namely fast passivation of the electrode by thin films, can be easily overcome in a potential sweep rate dependent manner. Indeed, at potential sweep rates as low as 20 mV.s⁻¹ films of up to 1.3 µm in thickness can be obtained in a one-pot process after 100 CV cycles on gold working electrodes. Lower potential sweep rates should be investigated in the future with the possibility to get even thicker films but at the cost of longer electrodeposition time.

The major attributes of melanin materials based on catecholamines and 1,8-DHN are summarized in Figure 7.

In a more explicit manner, the principal engineering attributes of eumelanins and allomelanins are summarized in

Table 1. Main engineering possibilities of catecholamine- (leading to eumelanins) and DHN- (leading to allomelanins) based materials.

	Catecholamine	DHN
Spherical nanoparticles	Requires templating molecules [23].	[33]
Anisotropic nanomaterials	PDA nanofibers in the presence of folic acid [42,43].	5 to 10 µm length platelets from the 4,4′-DHN dimer [38].
Porous nanomaterials	Requires sacrificial cores as templates for deposition [45,46].	Easy to proceed by single solvent change after the synthesis [44].
Paramagnetic properties	[35,36]	[39,41]
Versatile film deposition on solid substrates from solution using oxidants	One step process [47] for almost all catecholamines (with DHI as an exception [61]) on almost all kinds of substrates but with some surface specific effects [56].	Not possible. Should be tested in the presence of amines since cathechols mixed with diamines yield films in the presence of an oxidant [66,67,68].
AISSP deposition	From DHI [73].	From 1,8-DHN [37] and from its dimers [38].
Electrochemical deposition by CV and CA	[76,77,78,79,80,81,89]	[88]
Electrochemical sensing on films (and gels) incorporating melanins	[98,101]	[98]

with some relevant (but not exhaustive) references used in this article.

Overall, it appears that eumelanins (obtained from the oxidation of catecholamines) and allomelanins (obtainable from the oxidation of DHNs, but not exclusively [21]) can be used as nanomaterials (and are indeed used by living organisms in that from) or engineered to films. Film formation can be achieved via the AISSP method (applicable to both catecholamines and 1,8-DHN), by direct deposition from solution in the presence of an oxidant (limited to catecholamines as primary or secondary amines are required) and by electrochemical deposition. This latter deposition method, even if it requires a conductive substrate, seems to be the most versatile with respect to the target molecule: catecholamines, polyphenols or 1,8-DHN. From this perspective, it is mandatory to investigate the possibility of depositing films from the different isomers of DHN and derivatives such as naphtoquinones. Such investigations would allow for the comparison of solution redox chemistry, where the structure–property relationships have been investigated for some DHNs [39], and interfacial redox chemistry. It is not excluded that the non-electrochemical crosslinking steps following the initial oxidation will proceed according to different reaction mechanisms when the species are restricted to an interface rather than free to diffuse in solution.

It is apparent that the amount of available literature on the redox chemistry of catecholamines is much larger that on the redox chemistry of DHNs. This comes most probably from the much longer period of interest in the former molecules than in the later ones. The fact that the oxidation of the DHNs in solution does not directly yield to coatings, as is the case for many catecholamines, may constitute a limit (to potentially be overcome) of DHNs. But the apparent large versatility in the control of DHN-based nanostructures constitutes a major motivation to investigate the redox chemistry and subsequent self-assembly of DHNs.

Overall, the nanomaterials obtained by the controlled oxidation of catecholamines and DHNs may offer fascinating opportunities in biomaterials science (as antioxidants, photothermal agents and antimicrobials) and even more so in bioelectronics, in energy storage and conversion processes, as already suggested [17,101]. Achieving this potential would require a stronger research focus on DHN-based allomelanins, which offer greater tunability than the corresponding catecholamine-based eumelanins, except for their inability to directly form films in the presence of an oxidant.