How creating a microscopic saddle can unlock the ‘pigments of life’

1 Feb 2018

Image: sharon kingston/Shutterstock

Two studies have independently achieved major chemistry breakthroughs, including how to reconfigure the ‘pigments of life’.

Two teams of researchers from Trinity College Dublin (TCD) have recently made major breakthroughs in the field of chemistry, potentially opening new doors to drug developers and cancer researchers.

The first of the breakthroughs was achieved by a team led by Prof Mathias O Senge that discovered how to reconfigure porphyrins – the ‘pigments of life’ – which have long held untapped potential as useful players in the fields of cancer therapy, solar energy and materials science.

Porphyrins are organic compounds responsible for the green colour of leaves and the red colour of blood. All of their functionality is based along the same core chemical structure: four smaller rings connected to one larger ring, with a little cavity in the centre.

So, in order to carry out their typical functions – such as photosynthesis or carrying oxygen in blood – they host different ‘guest metals’ that include magnesium, iron, cobalt and nickel in the centre of the molecule.

Each of the different metals set off a different function referred to as a metalloporphyrin, which can perform some remarkable functions once pushed beyond its normal limits.

In a paper published to ChemComm, the five researchers discovered that by overcrowding the large porphyrin ring, they could force it to turn inside out and change into a shape similar to a saddle. This enabled the team to exploit the special properties of the formerly inaccessible core.

“Soon, we hope to tailor porphyrins according to specific requirements and use our rational design approach for various applications in chemistry, biochemistry, physics and beyond,” Senge said.

Thinking inside the box

The second of the discoveries helped to solve a decades-old challenge involving the development of new tools for a synthetic molecule known as a cubane.

Widely used in the pharma industry, cubane molecules consist of eight carbon atoms arranged at the corners of a perfect cube. They have proven very difficult to handle in terms of their reactivity, despite their simplicity in shape.

But now, in a paper published to the international journal Chemistry – A European Journal, the team of researchers, also led by Senge, revealed how it discovered how to circumvent the inherent reactivity of the cubane core through a process of filling the empty cubane toolbox.

This allowed the team to establish new connections and craft important residues onto the cubane scaffold, opening up possibilities for drug developers to create new, more diverse therapeutics from cubane and its derivatives.

Ironically, Senge said, he was impressed that his students decided to ignore his advice and think ‘inside the box’.

“We have a structurally unique building block which has been neglected by the majority of synthetic chemists up to now, precisely because this cube is so difficult to work with,” he said.

“However, with great risk comes great reward. I am delighted with our present success and intrigued about the avenues it will open in fields ranging from new drug discovery to 21st-century computer chip generation.”

Colm Gorey was a senior journalist with Silicon Republic