Stability of Organic Molecules: Lessons from Vitamin C

The stability of organic (carbon-based) molecules is an interesting and challenging topic as there are many different types of functional groups, molecular configurations, and molecular collisions to consider. Research on the stability of ascorbic acid (Vitamin C) and other vitamins demonstrates which factors to consider when it comes to the preservation of carbon-based molecules. Ascorbic acid is a very important but very unstable organic molecule which is characteristic of the class of organic molecules we know as vitamins (Fig. 1).

Figure 1: Ascorbic Acid, better known as Vitamin C, is an unstable organic molecule that is highly water soluble.

Vitamin stability has been studied for decades under a variety of storage conditions, and it is interesting to see how chemical manufacturers address long term stability issues. As stated on the website of DSM (a chemical company located in the Netherlands): “The vitamin manufacturing industry has developed products of high purity and quality, with improved stability, high bioavailability and optimum handling and mixing properties…. However, when dealing with complex and reactive compounds such as the vitamins, no product form can offer complete and unlimited protection against destructive conditions, excessive periods of storage or severe manufacturing processes. The individual feed manufacturer must take responsibility for assuring customers that vitamins have been stored, handled and added to feeds in an optimum manner and that vitamin levels are routinely monitored for quality assurance.”

Temperature, water content, pH, oxygen levels, light (type/intensity), catalysts (metals like Fe, Cu, etc), inhibitors, chemical interactions, energy (heat), and time are all factors that affect the stability of organic molecules. Double bonds and other functional groups are susceptible to rearrangements and reactions that vary with these conditions and is why organic chemistry textbooks are so thick! Vitamin C is somewhat stable in a dry, powdered form but dilution in water greatly accelerates the transformation of ascorbic acid into a biologically unusable form. Low pH’s can slow this degradation but at neutral to higher pH, dilute solutions of vitamin C can degrade very quickly. Every organic molecule has its own conditions of stability. In general, UV-light and oxygen are constantly attacking these molecules and rearranging their structures into molecular configurations unsuitable for their original purpose. Water speeds the degradation. This is why many vitamins and pharmaceuticals are packaged in thick, dark containers with desiccants.

Eliminating water, oxygen, and energetic radiation (gamma, x-ray, UV, visible) can greatly extend and preserve organic molecules which is why some biomolecules can be preserved for longer periods of time when embedded in crystalline or amorphous solids like amber or stone. Scientists have tried to mimic natural means to preserve biochemical molecules through the use of sugars like trehalose. Trehalose can help enzymes and proteins preserve their activity when lyophilized (freeze-dried) together. Other sugars and polyols have been explored as a partner chemical that provides many hydrogen bonding sites that stabilize the complex 3-D structure of proteins, enzymes, and nucleic acids in the absence of water but trehalose seems to be one of the best.

Water Bears (tardigrades) (Fig. 2) have been in the news lately because new information about their genome relating to their ability to survive harsh conditions such as absolute zero, vacuum of space, and high temperatures around volcanoes was recently published.

Scanning electron microscopy images of the extremotolerant tardigrade, Ramazzottius varieornatus, in the hydrated condition (a) and in the dehydrated state (b), which is resistant to various physical extremes. Scale bars, 100 μm. From Hashimoto et al., 2016, Nature Communications, 7, 12808 (Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License).

The November 7, 2016 issue of Chemical & Engineering News featured this recent research as it interests chemists and engineers who are trying to find innovative ways to preserve unstable carbon-based molecules of life: “Although commonly found in moss and lichens, tardigrades are truly aquatic animals, requiring a film of water surrounding their body to take in oxygen and expel carbon dioxide. Without water, they dry out, practically cease metabolism, and curl up into a sturdy desiccated form called a tun. It is the tun state that enables tardigrades to withstand many extremes. And then if they return to water, they bounce right back.” It is believed that tardigrades produce various “dry-tolerant proteins” that “are intrinsically disordered in water but develop secondary structures in the dehydrated state that allow them to stabilize DNA, proteins, and cell membranes.”

Carbon-based chemistry in living systems is constantly under thermodynamic and kinetic distress from heat, light, radiation, oxygen, water and other reactive chemicals that limits their longevity. This is to say nothing of the enzymatic biological attacks from the microbial world that slice-and-dice organic chemicals in an effort recycle them for their own energetic requirements. The same flexibility that allows living systems to constantly recycle and renew carbon-based materials are the same mechanisms that inhibit long term stability.

Ryan T. Hayes is a Ph.D. chemist (Andrews University) studying how to preserve vitamin C and other biomolecules through the use of spherical nanopolymers called dendrimers.