[galpinj]

Hey everyone,

I've been going crazy trying to better understand some basics of chemistry, and I'm hoping someone here can enlighten me. I think I have a pretty good understanding of redox reactions and electronegativity, but I can't consolidate some basic ideas.

I was looking at how NAD+ gets reduced into NADH by different oxidizing agents. For example, ethanol can get oxidized to ethanal, at which point a hydride (H-) ion will be transferred over to NAD+. In this example, the hydrogen atom is attached to a carbon, which is (slightly) more electronegative than hydrogen. What causes the hydrogen to take both electrons in this instance? And, on a more conceptual level, what is the determining force behind an atom keeping both electrons, losing both electrons (homolytic vs heterolytic breaks)? I can't seem to understand what causes the elements to behave one way or another.

Furthermore, a different hydrogen (on the hydroxide of the ethanol) also drops a hydrogen ion, but this time as an H+, thus creating a negative Oxygen ion that double bonds with carbon. Why does the hydrogen drop like this? What is the advantage of giving up the hydrogen and forming a double bond with carbon? From what I understand, oxygen would have more control of the electrons shared with hydrogen than those shared with carbon, so wouldn't OH be more stable?

This link from Khan Academy shows the ethanol -> ethanal reaction. Again, this is just one of many examples I have run into. I can't understand why the molecule makes these changes, and what is the underlying force.

https://www.khanacademy.org/test-prep/mcat/chemical-processes/alcohols-and-phenols/v/biologic-redox-reactions-of-alcohols-and-phenols?v=0w96SqrvVjw

[thetada]

First up, I wouldn't call these basics.

In terms of the driving force of these situations, it's all about the thermodynamics. From my 4th ed copy of Biochemistry by Stryer: "A thermodynamically unfavourable reaction can be driven by a thermodynamically favourable one." For example, we summarise the process of photosynthesis as the combination of carbon dioxide and water to produce glucose. Bubbling CO₂ through water will not make glucose, becuase it is thermodynamically unfavourable. In fact, plants harvest energy from the sun, which powers a huge series of interrelated reactions, each of which relies on catalytic enzymes. So the plants achieve the thermodynamically unfavourable production of glucose, by breaking it down into a series of thermodynamically favourable steps.

I was looking at how NAD+ gets reduced into NADH by different oxidizing agents. For example, ethanol can get oxidized to ethanal, at which point a hydride (H-) ion will be transferred over to NAD+.

A species is reduced by a reducing agent, not an oxidising agent. As you note, ethanol is oxidised into ethanal, meaning that NAD+ is the oxidising agent. Meanwhile, as NAD+ is reduced, ethanol is the reducing agent.

And, on a more conceptual level, what is the determining force behind an atom keeping both electrons, losing both electrons (homolytic vs heterolytic breaks)?

This is not the difference between homolytic and heterolytic. Both of the examples you mention are heterolytic, because the atoms between which the bond is cleaved end up with different numbers of electrons (2 electrons with one atom, 0 with the other). Homolytic fission is what happens during radical reactions, which is when the cleaved atoms get one electron each from the bonding pair of electrons.

In this example, the hydrogen atom is attached to a carbon, which is (slightly) more electronegative than hydrogen. What causes the hydrogen to take both electrons in this instance?

We ought to consider the reaction in tandem with the enzyme alcohol dehydrogenase, which acts as a catalyst. The active site of the enzyme has a coordinated Zn²⁺ ion. The positive zinc ion is attracted to the partially negative oxygen atom in the ethanol. Various deprotonation events take place in the enzyme, which culminates in the deprotonation of the hydroxyl hydrogen atom. All of this sets the scene for the hydride transfer from the deprotonated ethanol to the positively-charged NAD+. Interestingly, my copy of Stryer says the "NAD+ accepts a hydrogen ion and two electrons, which are equivalent to a hydride ion." This suggests that the two electrons do not, in fact, come from the bonding pair of the cleaved bond. Honestly, I don't know.

The reaction is complicated but ultimately, it's all about electrons being transferred from electron rich areas to electron poor areas. Although the hydroxyl-bonded carbon atom in the ethanol has a partial positive charge, the NAD+ has a full positive charge, which will be more attractive to electrons, so we can rationalise the transfer of the bonding electrons in that sense. However, that's a simplification of a far more elaborate process.

I recommend that you consider the oxidation of alcohols and the reduction of aldehydes / ketones / carboxylic acids with inorganic reagents, like the oxidising agent potassium dichromate and the reducing agent sodium borohydride. These will have simpler mechanisms that should be more readily comprehensible.

[Babcock_Hall]

It is thermodynamically favorable for NADH to reduce ethanal, and that is what happens in yeast.  On the other hand, ethanol gets oxidized in our bodies to ethanal, and then this aldehyde gets further oxidized (one type of biochemical coupling is removal of a product).  The catalyst is alcohol dehydrogenase in either organism.  Most reactions of biological importance involving NAD/NADH are hydride transfers.  However, there are a few instances in which radical chemistry occurs.

[galpinj]

Thank you so much everyone,

I should have double checked my question before posting, as it seems I made a few slip-ups. Your explanation really helps thetada, and I will try to find the textbook you outlined to get some more information. Regarding homolytic and heterolytic cleavages, I meant to ask what causes an atom (like hydrogen) to keep none, one, or both electrons; however, your explanation regarding NAD+ charge and, especially, the positive charge of cofactors like Zinc seems to explain why two electrons were taken with the hydrogen in this instance. You really helped to explicate why the molecule would undergo this reaction.

Thank you

[Enthalpy]

Just as a short comment, I wouldn't try to apply thermodynamics to photosynthesis, because photoreactions are very far from thermodynamic equilibirum.

[thetada]

Happy to help galpinj

Enthalpy, I'm very interested by your comments. It might have been better if I'd referred to the light-independent reactions involved in the photosynthetic production of glucose. One thing interests me though, life is generally considered to be far from equilibrium, but we assign free energy changes to the various biochemical processes that combine to effect it. Are you saying that thermodynamic principles are limited in what they can usefully say about photosynthesis, or that application of the principles is invalid?