Building a better vitamin: Antioxidant structure

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  • Published: Sep 15, 2014
  • Author: David Bradley
  • Channels: X-ray Spectrometry
thumbnail image: Building a better vitamin: Antioxidant structure

Radical idea

Synthesis, spectroscopic characterization, crystal structure, DNA interaction study and in vitro biological screenings of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid

Researchers have synthesized the antioxidant compound 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid and obtained a crystal structure. The molecule has comparable antioxidant activity comparable to that of vitamin C, ascorbic acid, as well as demonstrable antitumour activity.

Muhammad Siraj ud-Din, Nooruddin, Saqib Ali and Shahan Zeb Khan of the Quaid-i-Azam University, in Islamabad, Pakistan, Vickie McKee of Loughborough University, Leicestershire, UK and Khan Malook of the University of Peshawar, also in Pakistan, explain in the journal Spectrochimica Acta Part A how they have carried out a elemental analyses, obtained a single crystal X-ray structure and undertaken Fourier transform infrared, proton and carbon-13 nuclear magnetic resonance spectroscopy on an intriguing small molecule.


The compound is, they demonstrated stabilised by short intramolecular OAH---O hydrogen bonds within the molecule while the crystal structure reveals intermolecular NAH---O hydrogen bonds forming zigzagging chain links between molecules in the crystal giving rise to a dendrimer-like structure. Such a dendrimeric packing arrangement is important to research in pharmaceuticals because it can act as a tool for drug delivery where the molecules insert into DNA base pairs while interacting via the intercalative mode. Such a property points to a possible explanation for antitumour properties as such intercalation damages DNA and would prevent target cancer cells from replicating successfully.

Carboxylic acids, of which this compound is an example, are widespread in industry, in food production, pharmaceuticals, surfactants, detergents so-called "green" solvents. They represent a vast realm of organic chemistry ranging from the simplest, formic acid, commonly released by ants when they bite and used in chemical manufacturing to the highly functionalized structures such as the present example and many others used as pharmaceuticals, for instance.

Acid comments

This particular carboxylic acid can offer up its electrons to free radicals and as such it has antioxidant properties in the body that on a par with the well-studied and vital ascorbic acid, more commonly known as vitamin C. The search for potent antioxidants to be used in dietary supplements and functional food in a quest to ward off cancer and degenerative diseases triggered or exacerbated by free radicals and other oxidizing agents in the body is ongoing, although not without controversy. Natural plant chemicals, phytochemicals have been demonstrated as having anticancer properties as well as seeming to reduce the risk of cardiovascular disease and even slowing the aging process. Whether or not we need to supplement our natural intake from fruit and vegetables is a different matter, after all, antioxidant overload might also mop up useful free radicals that are the first line of chemical defence against invading pathogens.

However, more specialized antioxidants that would be needed at lower dose and also have additional direct benefits might be useful nevertheless. Sirajuddin and colleagues report details of their compound's interactions with DNA, its cell-killing, cytotoxic and antitumour properties as well as its prowess as an antioxidant, as demonstrated by reaction with the model free radical 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in which it quenches the radical at lower concentration than is needed with vitamin C.

"The synthesized compound may well be a useful pharmaceutical," Siraj ud-Din told SpectroscopyNOW. "However for it to have a market value, the compound will need to be tested in industry to confirm its properties," he adds.

Related Links

Spectrochim Acta A Mol Biomol Spectrosc 2015, 143, 244-250: "Synthesis, spectroscopic characterization, crystal structure, DNA interaction study and in vitro biological screenings of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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