Indigo: from blue jean dyes to next generation medicine
by Dennis Chung-Yang Huang in Chemistry

Many shades of indigo photoswitches

Indigo is a dye that has been used for thousands of years. It's unique properties suggest that it could help pharmaceutical drugs respond to light and only activate in specific parts of the human body. Dennis Chung-Yang Huang explains 'indigo photoswitches' and its potential application in chemotherapy.

Dennis Chung-Yang Huang

Dennis Chung-Yang Huang

Dennis has recently completed the postdoctoral research stay at Humboldt-Universität zu Berlin, where he developed a new class of indigo photoswitches.  His research interests include synthetic organic chemistry, transition metal catalysis, and molecular photoswitches. Outside of chemistry, his two greatest passions are playing softball and watching movies.

Are you wearing blue jeans today? If so, then you’re carrying around one of the most ancient dyes known in human history: indigo.

With its early usage dated back to more than 6000 years ago, indigo has served as an important dye across numerous civilizations and geographical regions. Back in the old days, indigo was extracted and processed from plants, mainly from one called Indigofera tinctoria, primarily grown in India (hence the name, indigo). However, following the advent of blue jeans, the natural supply could no longer satisfy the growing demand of this blue dye, so it soon became imperative to produce indigo industrially.

In the late 19th century, German chemist Adolf von Baeyer developed several ways of synthesising indigo that became the foundation of today’s dye manufacturing. In fact, he was awarded a Nobel Prize in Chemistry in 1905 for his contribution to organic dye chemistry. To date, several thousand tons of synthetic indigos are being produced annually.

Now, the good old Indigo dye leads a completely new life. But before jumping right into it, we need to first explain another concept: photochromism. “Photo” means light and “chrom” means colour, so this term refers to a peculiar phenomenon where something changes colour under light in a reversible manner, so that it can return to its original colour when the light is turned off or when the light of a different wavelength is applied. Perhaps the most well-known application of photochromism is the photochromic sunglasses that darken outdoors under the sunlight and revert back to being colourless indoors. Generally speaking, photochromism indicates that an object has two states, like the colourless and darkened sunglasses, that are interconvertible by light.

Separation of different indigo-based photoswitches

This two-state process is just like switches that we use in daily life: it’s like switching a machine on and off, or a lightbulb, or a water faucet. What makes photochromism special is that it’s light who does the “switching”. For this reason, we call these objects photoswitches. Photoswitches offer scientists a powerful tool for controlling molecular processes: light is non-invasive in many experiments of interest, and its properties can be precisely adjusted with ease (thanks to advances in optical technologies!).

Researchers also take advantage of the differences between the two states of photoswitches to make exciting new discoveries. For example, scientists blended azobenzenes, a common type of photoswitch, with liquid crystals, producing a thin film that bends or stretches depending on the type of light shined onto it.

Right now, scientists are considering another exciting application of photoswitches in the field of medicine. Their goal is to address the side effects of chemotherapy such as nausea and hair loss, which result from the unselective toxicity of drugs targeting both cancer cells and normal tissue. The idea is to design a drug that is normally inactive and can only be activated on demand in the human body by light. This approach would allow physicians to “switch on” drugs selectively at the location where the tumors reside. When the drug leaves the tumor cells, it will automatically deactivate and thus pose no threat to healthy cells. This concept, now termed photopharmacology, is related to so-called photodynamic therapy, where high-energy oxygen species are “switched on” by light around the tumor cells.

However, in order for the drugs to be activated inside the human body, light needs to penetrate people’s skins and tissues to reach them. Obviously, light doesn’t really go through human bodies (that’s why you don’t look transparent under the sun). But it turns out that certain wavelengths, such as red and infrared light, can reach inside your body more deeply than others. Try holding a laser pointer behind your palm, and you will see some red light leaking through your skin. To this end, photoswitches that can be switched on by red or infrared light are ideal for this application, in addition to their benefit of being lower in energy and thus less harmful to human bodies.

And here’s where indigo comes in! (Did you really think I’d forgotten?) Since it’s a blue dye, indigo naturally absorbs red or reddish light. You see, indigo itself doesn’t actually undergo photoswitching, which is a good thing because no one wants their blue jeans to be changing colour under sunlight (hello, million dollar idea).  However, after some simple modifications to its chemical structure, we can actually make indigo into a photoswitch that can change colour under the influence of red light.  Depending on their chemical structure, these aesthetically appealing molecules can appear anywhere from red, pink, blue or green, which makes working with them extremely fun! Aside from being pretty and originating from dirt-cheap starting materials, one advantage of photoswitches based on indigo is that by switching them, we can dramatically change the spatial arrangement of atoms within the molecules.  More specifically, you are able to move two parts of the molecules from totally far away to right next to each other.  This character can potentially be very attractive in photopharmacology, for example, by designing drug molecules that are active only when two components are close in proximity.

In fact, we’ve known about indigo photoswitches for more than 50 years, but they have so far received much less attention than other classes of photoswitches. This may be because of their distinct photochemical properties, such as how quickly the switched state returns to the original state. Scientists are currently working on addressing these issues while finding novel applications. We hope to one day teach old dogs new tricks, or in this case, shine new light on old dyes!

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