Anslyn pp. 259 – 296


p. 259 — Looking forward to seeing how the pKas of the following
Acetylene 25
NH3 33
Di-isopropyl amide 35
Toluene 40
Benzene   43 (50 C1070)
Methane  48
Butane 50

     are actually defined. 

    1 proton in a liter of water from H-A would only have a pKa of only 16 or so. 

p. 260 — I’ve always thought that the terms acid/base conjugate acid/conjugate base was meaningless, and a source of unnecessary confusion .  All 4 are in equilibrium and what you call each of the 4 moieties depends on where (out of equilibrium) you start. 

p. 261 — Note that Ka as defined in equations 5.7 is really a dissociation constant (Kd) as defined in the previous chapter. 

p. 263 — Ah the Henderson Hasselbalch equation — important in med school, if not medicine itself.  The body maintains blood pH in a very narrow range (7.36 – 7.44) because blood is so highly buffered (hopefully A & D will talk about this).  No they don’t. Buffer is not even in the index.  So I will.  

I don’t know if people still do titrations with a beuret, but if you have done one, you know how infinitesmal the amount of acid you have to add to get a color change at the critical point.  To change ph 7.36 to 7.44 to 7.36 takes under 10 microMoles of protons.   Metabolizing glucose (neutral) to CO2 (acid when dissolved in water) happens all the time in the body.  It gets worse when oxygen isn’t around for the final steps, and lactic acid is produced.  This is why anoxic patients are so acidotic.

Anyway, suppose you add 100 milliMoles of an acid whose pKa is around 7 to water.  It then takes 100 milliMoles of acid to change pH by one unit.  That’s what buffers are all about, and the body is full of them. 

p. 266 — “Therefore, now, new acidity scales are needed, giving a measurement of the effective ability of the concentrated solution to donate protons to an organic compound, just as the pH is the ability of a dilute acid solution to donate protons” — should add “to water”.

p. 267 “too weak of a base” — Oh, well, Anslyn teaches in Texas.  They seem to be teaching him. 

p. 273 — Nice to see some actual values for pKa’s inside proteins.  However the reference is 19 years old.  Isn’t there some more recent data?  Describing how the pKas were determined would be interesting.

p. 274 — Gas phase ‘acidities’ seem to be a rather bizarre construct.  They do tell you something about anion stability. 

p. 276 — So that’s how they determine pKa’s over 16 ! !  It reminds me of the distances scales astronomers use, the farther out you go, the more assumptions you must swallow.  Parallax is pretty straightforward, then come Cepheid variables, red shifts and on and on. 

p. 284  “The princple  influence is the hybridization of the carbon.”  Who learned you,  boy ! 

p. 286 — The structures shown for glutamic acid, aspartic acid, lysine and arginine are worthy of my first organic chemistry textbook circa 1957 — English and Cassidy.

p. 287 — Hoogsteen hydrogen bonding between A and C requires that the cytidine be protonated.  As the pH is lowered below 7 (to pH 5 and 6), triple helical DNA formation is enhanced.   Very nice — didn’t know this. HoweverI doubt that this occurs in vivo.  The body keeps pH very tightly controlled.   You’re practically dead when blood pH goes below 7.0.  However some compartments of the body (think gastric acid in the stromach with its pH of 1) have low pH.   The pH of the cytoplasm of cells is between 7.0 and 7.4, that of the nucleus is held to be .3 – .5 pH units higher (http://jcs.biologists.org/content/109/1/257.short) so it’s unlikely that this is relevant physiologically, fascinating though it is. 

p. 288 — Nice discussion of Lewis acid/base, vs. electrophile/nucleophile.  However, Clayden somewhere gave the example of an anion R2N:- which was a great base, but a lousy nucleophile because it was so sterically obstructed.

p. 289 — Good to see the correlation between polarizability and softness of the nucleophile — I don’t think Clayden ever said so. 

p. 291 — second paragraph second to last line ‘nuclephilic’
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