Dr. Albert Szent-Gyorgyi, the brilliant scientist who won the Nobel Prize in 1937 for his discovery of vitamin C, also advanced what I would call a true theory of life in two of his last publications. Szent-Gyorgyi (1978, 1980) asserted that energy exchange in the body can only occur when there is an imbalance of electrons among different molecules, assuring that electron flow must take place. Natural electron donators give up electrons to natural electron acceptors. Szent-Gyorgyi maintained that dead tissue had a full complement of electrons, a state in which no further exchange or flow of electrons could take place.
Another way of viewing this is that brisk electron flow and interchange equals health, impaired or poor electron flow and interchange equals disease, and cessation of flow and interchange equals death. Vitamin C, as the premier antioxidant in the body, is perhaps the most important ongoing electron donor to keep this electron flow at optimal levels.
Oxidation involves the loss of electrons, and an antioxidant counters this process by supplying electrons. Although vitamin C is the most important antioxidant in the body, there are many different antioxidants present in the body, and many of them work to keep the more important antioxidant substances in the body in the reduced state, which allows the donation of electrons. For example, vitamin E is an antioxidant that is fat soluble, which is important in allowing it to be the primary antioxidant present in the lipid-rich cell membranes of the body. Vitamin C, which is water soluble, helps to recharge oxidized vitamin E in those cell membranes back to the electron-rich reduced form. Even though vitamin C is not the primary antioxidant in the cell wall, it plays a vital role in maintaining the optimal levels of the metabolically active antioxidant, vitamin E, at that site.
It appears, then, that the local loss of electrons (oxidation) represents the primary degeneration, or metabolic breakdown, of the tissue or chemical substance losing the electrons. An antioxidant can serve to immediately restore this loss of electrons, resulting in a prompt "repair" of that acutely oxidized tissue. Also, an antioxidant can often neutralize the oxidizing agent before it gets a chance to oxidize, or damage, the tissue initially.
Joseph Weiss discovered in 1942 (3) that in certain molecular complexes an electron can go spontaneously from one molecule (the donor) to another (the acceptor), a reaction hc called "charge transfer." Weiss worked with complexes formed by strongly oxidizing and reducing agents. Later, attention was given to charge transfer in which the energy of light moves electrons from one molecule to another. This was called a "weak transfer" to distinguish it from the "strong" transfer studied by Weiss, in which the transfer was spontaneous. R. S. Mulliken cleared up the quantum mechanics of these reactions (4) and systematized them. He preferred the name "DA
[donor-acceptor] interactions" to "charge transfer."
Though in several instances DA interactions between biological substances have been produced in vitro, the idea of charge transfer found no real place in biology. Strong charge transfer could play no role because the presence of strong oxidizing agents is incompatible with life, and we have no light in our body to move electrons (except in the eye and skin). So charge transfer remained, for the hiologist, more or less a chemical curiosity.
Using the method of electron spin resonance (5). I could show that even molecules with low reactivity, which play a major role as metabolites or hormones, can give off a whole electron, forming a free radical; this suggested that charge transfer may be one of the most common and fundamental biological reactions. Such considerations led to the study of the nature of the various donor and acceptor atomic groups.
Donor and Acceptor Groups
The cell has a rich source of transferable electrons in its nitrogen, sulfur, and oxygen atoms, which all have pairs of "lone" electrons-electrons which do not take part in bonding and are thus available for transfer.
The surrounding world can be divided into two parts: alive and inanimate What makes the difference is the subtle reactivity of living systems. The difference is so great that it is reasonable to suppose that what underlies life is a specific physical state, the living state'.
Living systems are built mainly of nucleic acids and proteins, The former are the guardians OF the basic blueprint while the business of life is carried on by proteins. Proteins thus have to share the subtle reactivity of Living systems. A closed- shell protein molecule, however, has no electronic mobility, and has but a low chemical reactivity. Its orbitals are occupied by electron pairs which are held firmly. The situation can be changed by taking single electrons out of the system, This unpaired electrons, leaves half-occupied orbitals with positive electron holes, making the molecules into highly reactive paramagnetic free radicals, The reactivity of the system depends on the degree of its electronic desaturation. Electrons can be taken out of protein molecules by electron acceptors' in charge transfer'. When life began, our globe was covered by dense water vapor. There was no light and no free oxygen. Electron acceptors could be made out of trioses by concentrating their carbon atoms as carbonyls at one end of the molecule. The resulting methylglyoxat is a weak acceptor which made a low level of development possible. When light appeared, free oxygen was generated by the energy of photons. Oxygen is a strong electron acceptor. Its appearance opened the way to the present level of development. The transfer of electrons from protein to oxygen is effected by a complex chemical mechanism which involves ascorbic acid,
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CHARGE TRANSFER AND PERMITTIVITY
Electrons can be taken out of molecules by other molecules by means of charge transfer'. If two molecules are held close together so that their orbitals overlap, the two form a single electronic system in which the electrons can rearrange themselves. If an electron in molecule A can decrease its free energy and increase its entropy by going over to molecule B, it will tend to do so, leaving its own molecule behind with a positive charge. Molecule A; becomes a donor, while the acceptor' molecule B acquires a negative charge. The transfer of a whole electron to another molecule, where it stays put, is a rare event which occurs only in strong' charge transfer.
What mostly will happen is that the transferred electron or electrons oscillate between the two molecules. Depending on various factors the oscillating electrons may not divide their time equally between the two molecules but may spend, say, 1% more on A than on B. It is customary to say, in such a case, that only one hundredth of an electron has been transferred. Such a partial transfer of electrons may play a very important part in biology and contribute to the subtle adjustment of biological reactions. It may have also a major importance for the mechanism of evolution.*
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The creation of life demanded donors' and acceptors'. How do we find them? The universe has been transformed into one coherent system by the periodic chart of atoms of Mendeleev, the top rows of which are reproduced in Fig. 2. Where do donors and acceptors fit into this system? As we all know, this chart, which contains all the elements, consists of horizontal and vertical rows. Each horizontal row begins and ends with a noble gas. The noble gases are the most stable ones, and all physical systems tend to acquire stability. So all elements tend to resemble a noble gas by having the same number of electrons in their outermost shell. The elements on the right side of the chart have less, those on the left side have more electrons than the nearest noble gas; and so the former tend to take up electrons and the latter tend to give off electrons. Thus the former become electron acceptors, the latter electron donors. According to the table the best acceptors are fluorine and the other halogens. In fact, they are too strong as acceptors to be used by life, so for a good biological acceptor we have to turn to the next column, headed by oxygen, the universal biological acceptor. The energy driving life is derived from the transfer of an electron from hydrogen to oxygen.