Repairing hair, with the help of chemistry

Hair-care products rarely get shout-outs from Nobel Prize winners. But two-time chemistry laureate K. Barry Sharpless called the hair repair brand Olaplex the most interesting company, other than his own, that is based on the click chemistry that he and coworkers developed around the turn of the century—work that won Sharpless his second Nobel, in 2022.

Sharpless made the remark during his acceptance address for the 2019 Priestley Medal, a major award that recognizes achievement in chemistry. The prize is given by the American Chemical Society, which also publishes C&EN but is not involved in editorial decisions.

It’s quite the nod for a hair company, but perhaps deserved, since many personal care chemists credit Olaplex for creating a whole new category of ingredient: hair repair bond builders. Since Olaplex launched, many other companies have seized the opportunities in hair repair created by harsh shampoos, damaging color treatments, and safety concerns over formaldehyde, an ingredient in some hair products.

The biggest driver for hair repair and reconstruction products is the popularity of dyed hair, according to Jess Driver, a color stylist and hair educator at Flaunt Hair Boutique in Baltimore. Bright, bold, frequently changing color has moved from the fringe to the mainstream.

Most color treatments start with a bleach based on hydrogen peroxide and ammonia, Driver says. “I think we’re seeing this huge push in the reconstructive market because so many people are using so much more bleach on their hair over and over again, and that is by far the most chemically damaging product that we use in the hair salon,” she says. Stylists and customers are also ditching the conventional hair repair method, keratin treatment, because it uses the toxic chemical formaldehyde to fuse proteins.

To understand hair damage and repair, you need to understand the chemistry of hair. It is a natural fiber, a complex and intentional biological structure made of a protein called keratin. Like any peptide or protein, keratin is a long polymer chain of amino acids. The amino acids are held together by permanent covalent bonds known as peptide bonds.

The amino acid chains coil up into springy fibrous helices. Disulfide bridges, another type of permanent covalent bond, link individual keratin molecules to form long fibers. The bridges are tough and chemically similar to the direct sulfur-sulfur bonds that vulcanize rubber. But peroxides, ammonia, and heat can break those S–S bonds, and there isn’t a good way to restore them.

The keratin fibers wind together in the inner part of the hair, the cortex, gripping one another with flexible hydrogen and ionic bonds. Melanin and other pigment molecules, including artificial hair colors, nestle up among the fibers of the cortex, Driver says.

Most bond-building hair-care ingredients focus on protecting or repairing covalent bonds, especially the disulfide bridges, because breaks there rob hair of its strength and bounce. Transient hydrogen and ionic bonds break and reform easily by design, especially in the presence of water, limiting their utility as a handle for hair repair.

Outside the cortex is a scaly exterior called the cuticle, which is also made mostly of keratin but is formed into scales instead of fibers. On its outside face, the cuticle has a hydrophobic lipid coating that makes it water resistant. On its inside face, lipoproteins glue the scales to the keratin fibers underneath.

Damage can happen at any of these structural levels. Olaplex’s main innovation is bis-aminopropyl diglycol dimaleate, a molecule that uses click chemistry to create a patch between the two ends of a broken disulfide bridge. Dean Christal, a personal care entrepreneur, founded the company in 2014 to commercialize chemistry developed by Eric Pressly and Craig Hawker at the University of California, Santa Barbara.

The company has had a dramatic decade. It spent 3 years fighting L’Oréal in patent courts over the personal care giant’s use of another molecule, maleic acid, to protect disulfide bonds during color treatments. The dispute ended in 2019, when a Delaware jury ruled that L’Oréal had stolen the patented chemistry and ordered it to pay Olaplex $91 million in damages.

A few months later, the private equity firm Advent International purchased Olaplex for $1.4 billion. The brand continued to grow, adding more products in hair repair and hair protection. In 2021, Olaplex went public with a stock offering that valued the company at around $14 billion.

Business has been rocky recently. A group of women who blamed Olaplex for hair loss sued in early 2023. Their claims were dismissed, but the possibility of more litigation has been a drag on the company’s stock, which currently trades at about 8% of its original price.

Another challenge for Olaplex is that the company’s success has drawn competition. Olaplex reported about $60 million in profit last year, well short of the $247 million and $221 million it brought home in 2022 and 2021, respectively.

The biggest name stealing Olaplex’s thunder is K18, which is also a hair repair brand built around an ingredient that bridges broken disulfide bonds. Rather than a small organic molecule, K18’s key ingredient is a peptide roughly 13 amino acids long. The firm launched a salon product in 2020 and made it available to consumers in 2021.

When disulfide bonds are broken, keratin fibers are less able to support one another, and that can lead to breaks in their peptide-bond backbones. K18’s patents describe peptides with up to five cysteines, the same amino acid that provides the sulfur in disulfide bridges. The firm says that each of its peptides binds multiple sites on the keratin it encounters, adding strength that a single disulfide patch can’t match.

That claim is backed up by informal online consensus that K18’s effects last longer than Olaplex’s. Driver tentatively agrees, with the caveat that she can’t know how well customers take care of their hair between visits. Also, she says, “even if you know exactly how all of the chemicals work in the process, everybody’s hair is completely different. A different size, a different shade, a different amount of pigment, a different thickness of cuticle.”

Olaplex has answered such competition with ingredients that protect disulfide bonds during bleaching and formulations that penetrate farther into the cortex.

Today, K18 and Olaplex are the biggest names in a field that is getting crowded. The biotechnology firm Caregen has a peptide-based bond builder with the cryptic name DR. CYJ iDR/pDR; the high-end brand Living Proof has a product it says works on covalent, ionic, and hydrogen bonds all at once; and Pressly, no longer with Olaplex, launched a bond-builder company in 2022 based on bis(2-ethylhexyl) maleate.

Bond builders can repair and prevent some of the damage done to disulfide bridges between fibers in the hair’s inner cortex, Driver says, which is important for people who color their hair over and over again. But there’s arguably a bigger opportunity to treat the outer layer, the cuticle, which could use support on nearly every head.

In healthy hair, the cuticle lies flat. When bleaches or shampoos strip off the lipids and lipoproteins, the scales lift up or even come right off. At the macroscale, a roughened cuticle means frizzy hair that tangles easily.

Flattening and restoring the cuticle is usually all that is needed for people who don’t color their hair or use other intense chemical treatments. “A lot of times when people think that their hair is damaged, it’s really just dry,” Driver says. When the cuticle isn’t lying flat, it also isn’t sealing in water.

Like bond builders, cuticle coatings are a competitive category. The ingredient maker Sharon Personal Care offers Sharohyal Moringa, which combines the sugar polymer hyaluronic acid with peptides extracted from Moringa seeds. Several chemical makers offer guar hydroxypropyltrimonium chloride, a modified polysaccharide that forms a thin film on the cuticle.

Silicones have been a stalwart ingredient for smoothing and sealing rough cuticles, but they’ve fallen out of favor over concerns about their biodegradability. Some silicones also build up, Driver says, eventually forming “a waxy coating on the hair that makes it feel rough and tangled.”

The chemical company Syensqo recently launched Dermalcare Avolia MB, a blend of avocado oil and an ester called isoamyl laurate. Oils and esters are established conditioning agents, but Syensqo says this particular pairing yields performance on par with that of silicones. The trick is to isolate each strand within a light layer of product, according to Jean-Guy Le-Helloco, the firm’s vice president for home and personal care.

Despite personal care chemists’ efforts, newer disulfide bond repairers and cuticle coatings aren’t as effective as the keratin treatment made popular by the brand Brazilian Blowout. It goes beyond coating by adhering new keratin scales to the outside of the cuticle using formaldehyde, which covalently cross-links protein chains at lysine residues. The hair ends up smoother and straighter, so keratin treatments are also popular with people who want to get rid of their curls.

“The way keratin treatment works is it coats the outside with heat-activated proteins that when you hit it with that hot iron, it basically hardens and solidifies and creates a new cuticle around the hair,” Driver says.

The treatment patches holes and adds new layers, but it’s harsh. “We would flat iron that hair at 450 degrees to create the chemical reaction,” Driver says. That kind of heat—about 230 °C—easily vaporizes formaldehyde, making the treatment abrasive for everyone in the room. “If somebody was doing it in the salon, even with the ventilation on and the doors open, you could see a haze, and it would sting,” she says.

Beyond its unpleasantness, formaldehyde is also toxic. The US Environmental Protection Agency says it causes cancer. On March 15, the agency proposed bans that would eliminate it from most industrial and consumer uses.

Avoiding formaldehyde takes chemical savvy, Driver says. Flaunt, the salon where she works, is formaldehyde-free. But that means scouring labels for formaldehyde synonyms, including methylene glycol, formalin, methylene oxide, formic aldehyde, methanal, oxomethane, and oxymethylene. It also means watching out for formaldehyde-releasing chemicals such as timonacic acid, which is also called thiazolidinecarboxylic acid.

Hair repair continues to attract new chemical ideas. One is from the synthetic biology start-up Curie Co, which recently launched an enzyme that catalyzes the formation of new peptide bonds, a reaction the firm says is gentler and more targeted than what’s offered by the formaldehyde-based keratin treatment.

CEO Erika Milczek says offering an enzyme instead of a stoichiometric reagent gives Curie Co an edge. “Quite frankly, it just comes down to cost,” she says. Formaldehyde is consumed in the cross-linking reaction; its carbon atom gets incorporated into the new bond. Because Curie Co’s product is a catalyst, each molecule should instead be able to make hundreds or even thousands of new bonds, helping it compete in terms of cost in use.

Milczek says potential customers are evaluating samples of the product, called Curamina, and test formulations are showing decreased frizz and enhanced color retention at concentrations between 1 and 4%.

Driver is glad to have better options in her work and that even more are on the way. In addition to bond builders, salons can offer keratin treatments that contain glyoxylic acid instead of formaldehyde. Researchers are still debating the chemical mechanism behind glyoxylic acid products. But the products do seem to smooth hair, Driver says, even if they take longer and suppress curls less than formaldehyde options do.

“Getting anything that could be potentially hazardous out of the salon is a big push for a lot of companies,” she says. Customers want to walk out of a salon feeling good about their choices, Driver says. “Hair is kind of a luxury industry at its core.”