Not many people realize this, but oxygen can be very toxic to human cells. Although we normally think of oxygen as being a life-sustaining gas, chemists like myself who have studied the electronics of oxygen molecules realize that there are multiple forms which oxygen can adopt. One of them is called “triplet oxygen”, and it’s the normal, healthy oxygen gas which we all need for respiration. It’s called a triplet state because two of the electrons in the molecular orbitals have identical spin states. Rules exist to govern the behavior of electrons, but unlike scientific laws, rules can be (and often are) broken. If the oxygen molecule is transported into a higher energy state, the two electrons can adopt a flipped orientation so that the two spins are opposite. This is called “singlet oxygen”, and it’s much more reactive than triplet oxygen.
Most molecules exist predominantly in the singlet state. For most compounds, the singlet state is more stable and therefore lower in energy. Oxygen is an exception to this rule, and so the more reactive, more energetic state is the singlet state. While normal triplet oxygen can be bubbled through organic solutions without much reaction, singlet oxygen has extra energy and is less stable; it undergoes all manner of reactions with it’s surroundings. The driving force is the extra stability it can gain by undergoing a reaction and then falling back down to the lower energy triplet state. In bodily tissues, oxygen plays a central role in providing energy to the cells but in it’s singlet state, it can wreck havoc. Cellular damage rapidly mounts as different components become oxidized until finally the cell cannot be repaired and it dies.
As a synthetic organic chemist who’s interested in photochemistry, I’ve been aware of this potential “dark side” to oxygen. I’ve used singlet oxygen to perform a wide range of chemical oxidations. It’s preparation normally requires a photosensitizer – a compound which absorbs light energy and transfers it to a nearby oxygen molecule, which bumps the electrons into the more reactive singlet state. The potential always existed in my mind for somehow generating singlet oxygen inside the body in order to selectively eradicate diseased cells. I was therefore very interested in a recent article published in Molecular Pharmaceutics, which is a journal published by the American Chemical Society. The researchers describe how they prepared nanoparticles out of a mixture of porphyrin compounds and polyacrylamide, which is a polymer that is compatible with human tissues.
The porphyrin units used by the British chemists were similar to those that are present in light-harvesting plant components. The researchers prepared tiny particles of polyacrylamide that were embedded with the porphyrins, which were then dispersed in a water solution. Adding this solution to a dish of colon cancer cells resulted in an incorporation of the particles into the structure of the tumor. The particles were tiny enough that they could penetrate the outer walls of the cancer cells, where they lie dormant, waiting to be signaled by incoming light. Exposing the cells to a laser light triggered the reaction, which used the energy from the laser irradiation to power the porphyrin sensitizers. These then transferred the energy to oxygen molecules present in the cells, kicking them into the singlet state. This (suddenly toxic) oxygen then rapidly killed the tumors through oxidative damage to the cellular components. This type of approach is very exciting to me as an organic chemist, because it shows how a careful arrangement of innocuous small molecules and inert polymers can (under the right conditions) become incredibly toxic to cancerous growths. I’m convinced that organic chemists have a central role to play in cancer treatment, and this publication was a step in the right direction.
The source of this article can be found at:
Lowry, A., et al. “Poly(acrylamide) nanoparticles as a delivery system in photodynamic therapy”. Molecular Pharmaceutics, 2011, 8, 920-931.