Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial. Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation. Generally, melanin is classified into five typeseumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelaninbased on the various chemical precursors used in their biosynthesis. Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified. Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins. In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melaninbased materials, while the synthetic analogues of other melanins have received far less attention. In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine. We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure−function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials.

Allomelanin is a type of nitrogen-free melanin most commonly found in fungi. Its existence enhances resistance of the organisms to environmental damage and helps fungi survive harsh radiation conditions such as those found on spacecraft and inside contaminated nuclear power plants. We report the preparation and characterization of artificial allomelanin nanoparticles (AMNPs) via oxidative oligomerization of 1,8-dihydroxynaphthalene (1,8-DHN). We describe the resulting morphological and size control of AMNPs and demonstrate that they are radical scavengers. Finally, we show that AMNPs are taken up by neonatal human epidermal keratinocytes and packaged into perinuclear caps where they quench reactive oxygen species generated following UV exposure.

Human hair is naturally colored by melanin pigments, which afford myriad colors from black, to brown, to red depending on the chemical structures and specific blends. In recent decades, synthetic efforts have centered on dopamine oxidation to polydopamine, an effective eumelanin similar to the one found in humans. To date, only a few attempts at polydopamine deposition on human hair have been reported, and their translation to widespread usage and potential commercialization is still hampered by the harsh conditions employed. We reasoned that novel, mild, biocompatible approaches could be developed to establish a metal-free route to tunable, nature-inspired, long-lasting coloration of human hair. Herein, we describe synthetic and formulation routes to achieving this goal and show efficacy on a variety of human hair samples via multiple spectroscopic and imaging techniques. Owing to the mild and inexpensive conditions employed, this novel approach has the potential to replace classical harsh hair dyeing conditions that have raised concerns for several decades due to their potential toxicity.

Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find artificial allomelanin analogues exhibit high intrinsic microporosity and describe an approach for further increasing and tuning that porosity. Notably, the synthetic method involves an oxidative polymerization of 1,8-DHN in water, negating the need for multiple complex templating steps and avoiding expensive or complex chemical precursors. The well-defined morphologies of these nanomaterials were elucidated by a combination of electron microscopy and scattering methods, yielding to high-resolution 3D reconstruction based on small-angle X-ray scattering (SAXS) results. Synthetic allomelanin nanoparticles exhibit high BET areas, up to 860 m 2 /g, and are capable of ammonia capture up to 17.0 mmol/g at 1 bar. In addition, these nanomaterials can adsorb nerve agent simulants in solution and as a coating on fabrics with high breathability where they prevent breakthrough. We also confirmed that naturally derived fungal melanin can adsorb nerve gas simulants in solution efficiently despite lower porosity than synthetic analogues. Our approach inspires further analysis of yet to be discovered biological materials of this class where melanins with intrinsic microporosity may be linked to evolutionary advantages in relevant organisms and may in turn inspire the design of new high surface area materials.

Recent reports suggest that next-generation hair dyes might take inspiration from the natural pigment melanin. In humans, melanin imparts color to hair and skin and acts as a natural sunscreen and radical scavenger, thereby protecting lipids and proteins from damage. The most commonly employed synthetic mimic of melanin is polydopamine, and its successful deposition on human hair was recently reported. Herein, we describe an enzymatic approach to synthetic melanin for dyeing human hair in a process that closely mimics part of natural melanogenesis. This chemoenzymatic method avoids the addition of a base and enables the implementation of several monomers beyond dopamine, including tyrosine, tyramine, and their derivatives. Critically, the enzyme provides a milder process for producing coated hair fibers than conventional chemical hair dyeing methods. In addition to providing natural coloration, these coatings have the potential to act as protective sunscreens that prevent photodamage of the inner hair fibers during exposure to sunlight. The protocols developed herein represent a mild and efficient route to nature-inspired multifunctional coatings. Such materials are promising candidates for artificial hair pigmentation and, more generally, could find extensive application as functional fiber coatings.

Commonly known as a skin pigment, melanin has a vital role in UV radiation protection, primarily acting as a radical scavenger. However, a lesser known natural property of melanin, observed in some melanized organisms, is its capacity to adsorb toxins, including metals and organic molecules. Inspired by this, we set out to generate a synthetic porous melanin that would pave the way to enhancing the natural adsorbent properties of melanin and melanin-like materials. Here, we developed a method for the synthesis of porous polydopamine-based melanin utilizing a mesoporous silica (MS) nanoparticle template and characterized its physical properties. Through the oxidative polymerization of dopamine, followed by the etching of silica, we generated synthetic porous melanin (SPM) with the highest measured surface area of any known polydopamine-based material. The prepared SPM was effective for the uptake of various gases and organophosphate toxins, with the material exhibiting high selectivity for CO 2 over CH 4 and high potential for ammonia capture. Given the demonstrated advantages provided by synthetic porous melanin and melanin's role as an adsorbent in nature, we anticipate the discovery of porous analogues in biological systems.

Melanin is a class of ubiquitous, heterogeneous, polymeric pigments. One of the most unusual features of melanin is the presence of stable persistent radicals, which has been reported to relate to ionizing radiation protection, including X-rays and gamma rays. In this work, we aimed to increase the radical content by introducing nitroxide radicals into synthetic melanin nanomaterials. Nanoparticles (NPs) were prepared by copolymerization of a stable radical modified monomer with the monomer dopamine. The radical content increased to 1 order of magnitude higher than that of the conventional melanin-like material, polydopamine. These radical NPs can enter human epidermal keratinocytes and form perinuclear caps, mimicking natural melanin synthesized by melanocytes. We demonstrated that these NPs display protective properties by scavenging reactive oxygen species, one of the most important biological effects of ionizing radiation exposure. This finding may have potential application for materials capable of mitigating side effects of clinical radiation therapy.

Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.