Category Archives: Anslyn & Doughterty

The new Clayden pp. 1134 – 1168

1135 — Mnemonic for nucleoTide vs. nucleoSide.  A nucleoTide has Three things — base + sugar + phosphate.  A nucleoside has only 2 — base + sugar.

1136 — Interesting idea of ATPylating a metabolic intermediate to make it more reactive — just like Tosylating an alcohol.  For lots more on ATP — see

Even though the post is over 2 years old it gets hits every day.  One fact to whet you interest — we make (and consume) half our body weight of ATP every day [ Nature vol. 417 p. 25 ’02 ] 

1136 — What is supercritical CO2 using to extract caffeine from coffee.

1136 — Excellent explanation of why S-adenosyl methionine (SAM) forms so easily — S being a soft nucleophile attacking at a primary carbon attached to a good leaving group (triphosphate).  A similiarly good explanation of why the methyl group of SAM is also attacked by many nucleophile metabolic intermediates to methylate them. 

1137 — It’s worth noting the way the sequence of bases on a single strand of DNA or RNA is read (by us).  The example shows two adenosine and a thymine linked together.  The sequence given is read as AAT, where the first letter has the phosphate on the 5′ and the last has it on the 3′.  Always read 5′ to 3′.    When DNA is copied, the coding strand is read this way which probably gave rise to the convention. 

1138 — There are other ways to G, A, T, C to pair with each other.  Look up Hoogsteen base pairing, and G quartet. 

1138 — Although DNA is more chemically stable than RNA, the current thinking is that life arose in an ‘RNA world’ with RNA acting to both store information, and to act as enzymes (RNAase P is the first known example of an enzyme whose active site is made entirely of RNA). 

1139 — No question that cyclic AMP is an important biological messenger (an undefined term which should have been), but so is cyclic guanosine monophosphate (cGMP). 

1138  The ribosome as the most elaborate structure in the universe.  Here’s some elaboration.  The hydrogen atom has a molecular mass of 1 Dalton.  The ribosome contains  about 4500 nucleotides (base + sugar + phosphate) and 50 proteins with a molecular mass of 2.5 megaDaltons.  The average mammalian cell contains 10,000,000 ribosomes. 

1141 I can’t believe a British textbook didn’t mention of James Lind when discussing scurvy.  He kneweth not vitamin C but by supplying limes to sailors, brought scurvy to an end in the British fleet.  It’s where the term Limey comes from.  

1143 — Sad that that a huge opportunity was missed to explain why glucose rather than most of the other 2^4 possible stereoisomers is used in cellular biochemistry.  It’s right there at the top of the page.  See if you can figure out why — answer at the bottom of the post. 

1145 — Med students love mnemonics.  The one for alpha and beta orientation at the 1 carbon of glucose is very good.  Alpha should stand for above, beta for below, but just the opposite occurs. 

1145 — While sulforaphane may reduce the risk of prostate cancer, it probably does so by decreasing androgen levels.  This may explain why vegetarian men are such wimps.  For details see —

1148 — The kink in oleic acid produced by the cis double bond is crucial for membrane function.  It essentially prevents the hydrocarbon tails of the saturated fatty acids found there, from perfectly aligning with each other and forming a liquid crystal.  This would cause all sorts of permeability and ridigity problems for the cell (since it is bounded by a lipid membrane). 

1153 Nice discussion of why thiol esters are so labile and why the body uses them. Ditto for why histidine is so often found at catalytic sites. 

1154 Be careful with pyruvate kinase.  The nomenclature is tricky.  There is a huge amount of organic chemical work being done to develop inhibitors of protein kinases, as they have been successfully used to treat cancer (Gleevec, imatinib).  Our genome codes for some 518 protein kinases (out of about 20,000 protein coding genes).  Protein kinases are enzymes which put phosphate on other proteins.  Pyruvate kinase is just the reverse, it takes phosphate from phosphoenolpyruvate and puts it on adenosine monophosphate form adenosine diphosphate. 

1161 — Again note that all the double bonds in the unsaturated fatty acids and polyunsaturated fatty acids (PUFAs) found in the body and shown here, are cis, for the same reason as given earlier (p. 1148)

p. 1162 — The acylation of acetyl coenzyme A with carbon dioxide is a rather remarkable reaction as CO2 is pretty inert.  More should be made of this fact. 

p. 1167 — Nice to see where the 4 membered ring in pinene (and other terpenes) comes from. 

At the end of the chapter several books are cited for more in the way of biochemistry.  I’d like to put in a plug for Voet’s biochemistry (full disclosure:  Don and I were good friends in grad school).  It’s a book for chemists and the pictures are great.  I don’t know that the others are inferior. I will say that I found Lehninger horribly dull.  If you want to see how dull Biochemistry was in the 50’s and 60’s, go to the library and look at Fruton and Simmonds. 

Answer — all substituents coming off the 6 membered ring are equatorial (except from #1 which can vary)

The end (of my reading of) Anslyn pp. 1000 –> End

No question, Anslyn & Dougherty “Modern Physical Organic Chemistry” is a great book and a labor of love.  Now that I’ve read the whole thing (not as well as I might have since I stopped doing the problems midway through in order to finish it in 2011) here are a few general comments to start off. 

l. It is extremely well written.

2. There should be an errata list.  They just incorporate known errors in the next printing.  For my thoughts on this see —

3. It would be nice, when referring to figures, equations, sections more than 100 pages back, to put in the actual page where they are found.  It would save a lot of time for those of us with less than an eidetic memory.

4. As mentioned early on, Tom Lowry told me a few years ago, that he thought Physical Organic Chemistry had died in the USA.  The book makes a strong argument that it is alive and well, because its ideas and techniques are  being applied to new areas undreamed of 50 years ago – photochemistry, solid state, conducting polymers, etc. etc.

5. All the beautiful electron pushing and orbital diagrams seem to come to a screeching halt when applied to organometallic chemistry, which has revolutionized synthetic organic chemistry, and which, to my view, along with NMR (and possibly computational organic chemistry) are the most significant new developments in organic chemistry in the last 50 years.

6 It must have been a labor of love.  Thanks for writing it.  My (sometimes snarky) comments are written in the hopes of making of making future editions even better.

A whiff of physics and mathematical idealization is seen right off — an infinitely long, perfectly linear, defect free — polyene.  Reminds me of the ‘consider a spherical cow’ of the old joke.  Chemists just don’t think this way.  

p. 1010 — “Organic students generally come away from introductory courses viewing benzene as the prototype conjugated pi system with all C-C bond lengths equal.”  I sure did.   Most neutral closed shell pi systems show alternating bond lengths. 

p. 1014 — What is 1 electronVolt in terms of the wave length of electromagnetic radiation?  I had to look it up — a wavelength of 4000 Angstroms has an energy of 3.1 electronVolts.  

p. 1017 — I love the retro Diels Alder approach to polyAcetylene — it’s so clever.  

p. 1022 — Thanks for clearing up the terminology concerning magnetism (ferro-, ferri-, antiferro- etc. etc.) and letting us know that there are 14 different kinds of it.

p. 1024 — Unfortunately, I found  the discussion of negative spin densities incomprehensible.

p. 1027 — There is no section 14.7.5

p. 1030 — Superconductivity is Newton’s first law of motion in action.   These’s guys are chemists not physicists. Hopefully they’ve talked to the physicists at Cal Tech and Austin (where numerous Nobelists reside) to make sure their explanation of superconducitivity is correct.  It’s the best I’ve seen.  I just hope it’s correct.  What starts the electrons all moving in the same direction in the first place? 

p. 1035 — Second harmonic generation has found great use in neuroscience.  Good to see organic chemists have helped.  Here is an example —       [ Proc. Natl. Acad. sci. vol. 103 pp. 786 – 790 ’06 ] Second harmonic generation (SHG) is used to measure membrane potential in dendritic spines.  (Dendritic spines are so tiny (on the order of a micron — that it is impossible to stick an electrode across its membrane without wrecking it).   SHG linearly depends on the electric field, which makes it suited to image membrane potential.   (ibid p. 3124 – 3129) — it can measure membrane potential in living cells with a spatial resolution of 1 micron and a time resolution of 1 milliSecond.  

      An important advantage of SHG for membrane potential recording is that the signal emanates from only properly oriented dye molecules in the plasma membrane.  Randomly oriented dye molecules bound to nearby intracellular or extracellular components don’t contribute.  Thus the signal response isn’t degraded by background as it is for fluorescence.  The signal response to changes in membrane potential is linear (as it is with fluorescence).    The problem is that there is damage produced by the light used (they either have to use a lot of light or a lot of dye to get a usable signal).

Anslyn pp. 935 – 1000

The penultimate chapter of Anslyn is an excellent discussion of photochemistry, with lots of physics clearly explained but it leaves one question unanswered which has always puzzled me.  How long does it take for a photon of a given wavelength to be absorbed .  On p. 811 there is an excellent discussion of the way the quantum mechanical operator for kinetic energy (-hBar/2m * del^2) is related to kinetic energy.  The more the wavefunction changes in space, the higher the energy.  Note that the wavefunction applies to particles (like protons, neutrons, electrons) with mass.

Nonetheless, in a meatball sort of way, apply this to the (massless) photon.  Consider light from the classical point of view, as magnetic and electrical fields which fluctuate in time and space.  The fields of course exert force on charged particles, and one can imagine photons exerting forces on the electrons around a nucleus and  changing their momentum, hence doing work on them.  Since energy is conserved (even in quantum mechanics), it’s easy to see how the electrons get a higher energy as a result.  The faster the fields fluctuate, the more energy they impart to the electrons.

Now consider a photon going past an atom, and being absorbed by it.  It seems that a full cycle of field fluctuation must pass the atom.  So here’s a back of the envelope calculation, which seems to work out.  Figure an atomic diameter of 1 Angstrom (10^-10 meters).  The chapter is about photochemistry, which is absorption of light energetic enough to change electronic energy levels in an atom or a molecule.  All the colored things we see, are colored because their electronic energy levels are absorbing photons of visible light — the colors actually result from the photons NOT absorbed.  So choose light of 6000 Angstroms — which has a wavelength of 6 * 10^-7 meters.

In one second, light moves 3 * 10^8 meters, regardless of how many many wavelengths it contains. If the wavelength were 1 meter it would move past a point in 1/3 * 10^8 seconds But wavelength of the visible  light  I chose is 6 * 10 ^-7 meters, so the wavelength moves past in 6*10^-7/3 * 10^8 = 2 x 10^-15 seconds, which (I think) is how long it takes visible light to be absorbed.  Have I made a mistake?  Are there any cognoscenti out there to tell me different?

That was a classical way of looking at it.  Now for the bizarrity of quantum mechanics.  How does the wavelength of the photon get sucked up by something 1/6000th of itself, particularly when there are probably at least 10^9 atoms in a volume 6,000 on a side?  It gets worse with NMR, because the radioWave absorbed by a nucleus is 1 meter, and the nucleus is 10^-4 the size of an atom.  Essentially I’m asking about the collapse of the wavefunction of a photon (assuming they have one?).


p. 936 — “We show wavelength in the condoned (italics) unit of nanoMeter  . . . “  It may be condoned, but this chemist thinks in Angstroms, and my guess is that most chemists do, because atomic radii and diameters are small numbers in Angstroms, not fractions of a nanoMeter.

p. 939 — “Absorption of two photons or multiple photons . . . does not occur, execpt with special equipment . . . “  True enough, but the technique is now widely used in biologic research.   This is not new      [ Nature vol. 375 pp. 682 – 685 ’95 ] In contrast to conventional microscopy, two long wavelength photons are simultaneously absorbed in two photon fluoresence microscopy (multiphoton microscopy)   < [ Science vol. 300 p. 84 ’03 — actually within a few femtoSeconds — I thought simultaneity was asking too much > and combine their energies to excite a fluorophore not normally absorbing at this wavelength.  This permits the use of infrared light to excite the fluorophore. By using low energy (near infrared) light rather than higher energy visible light photons, light induced degradation of biological samples is minimized.  

p. 939 — Manifold probably really refers to the potential energy surface associated with the different energy levels, rather than the numeric value of the energy level. 

p. 940 — Look at transition dipoles very hard if you want to understand Forster resonance energy transfer (FRET), whch is widely used in biology to determine how proteins associate with each other. 

p. 944 — How in the world did they get enough formaldehyde in the excited state to measure it — or is this calculation? 

p. 947 — Nice exposition on GFP (Green Fluorescent Protein) which has revolutionized cellular biology.   But the organic chemist should ask themselves, why don’t chemical reactions between the hundreds of side chains on a protein happen all the time?  For more on this point see

p. 951 — How do you tell phosphorescence from fluorescence — the lifetime for phosphorescence is much longer (.1 – 10 seconds), but is this enough. 

p. 970 — The chemistry of photolyases, which repair thymine photodimers is interesting.  Here’s a bit more information.        [ Proc. Natl. Acad. Sci. vol. 99 pp. 1319 – 1322 ’02 ] Enzymes repairing cyclobutane dimerase are called photolyases.  The enzymes contain a redox active flavin adenine dinucleotide (FAD), and a light harvester (a methenyltetrahydrofolate < a pterin > in most species).    It has been proposed that the initial step in the DNA repair mechanism is a photoinduced single electron transfer from the FAD cofactor (which in the active enzyme is in its fully reduced form — FADH-) to the DNA lesion.  The extra electron goes into the antibonding orbital of one of the C C bonds of the dimer.  (The electron donated is on the adenine of FADH).  The entire process takes less than a nanoSecond.   Electron transfer to the dimer takes 250 picoSeconds.  The dimer then opens within 90 picoSeconds and the electron comes back to the FADH cofactor in 700 picoSeconds.  This all happens because the dimer has been flipped out of the DNA into a binding pocket of the photolyase (how long does this take?).

       Interestingly, photolyases use less energetic light than the natural absorption of thymine dimers (2500 Angstroms).   Photoexcitation of the enzyme culminates in electron donation from the excited state flavin directly to the thymine dimer. 

p. 973 –> The photochemical reactions are impressive synthetically, and represent a whole new ball game in making fused rings.   The synthesis of cubane is impressive, and I wouldn’t have though quadricyclane could have been made at all. 

p. 980 — Caged compounds and their rapid release in incredibly important in biological research, particularly brain research.  Glutamic acid, is the main excitatory neurotransmitter in brain, and the ability to release it very locally in the brain and watch what happens subsequently is extremely useful in brain research.  

p. 987 — Sinbce the bond dissociation energy of O2 is given (34 kiloCalories/Mole) and C=O bonds are stated to be quite strong, why not just say the BDE of C=O is 172 KCal/M? 

p. 992 — Good to see Sam Danishevsky has somethng named for him.

Anslyn pp. 877 – 934 (Pericyclic reactions)

Everything is crystal clear, and not much to comment about.  

p. 900 — Interesting to see the semi-empirical and ab initio approaches disagreeing on the pericyclic transition states and the explanation for the difference.  This sort of stuff always bothers me about ‘black box’ approaches.  It’s clear that next year. I’m going to make a big effort to really understand computational organic chemistry and molecular dynamics simulations, particularly the latter, since all sorts of conclusions are reached using them in protein folding, drug protein interactions, ion channel and enzyme mechanisms, etc. etc. For a current example see  [ Neuron vol. 72 pp. 713 – 720 ’11 (December) ] where simulations are used to figure out how an ion channel in the membrane of all our neurons looks in the resting state.  Venoms and other poisons target these channels showing how crucial they are for life itself.  For how ion channels are related to a disease I battled:  epilepsy see

        How many grains of salt should I take reading these papers?  The many posts by Curious Wavefunction about computational chemistry are well worth reading (particularly his caveats), but all this takes me back to the days in neurology when we had precious little data, but would quote what various eminent authorities had to say about a given clinical issue.  It was like quoting scripture, hardly scientific, but it provided a certain comfort.  I’m presently in the same boat with the various computational approaches.  A&D are very good about their limitations, and what they sweep under the rug, but I’m going to try to go under the hood with Cramer’s book — “Essentials of Computational Chemistry”.  New Year’s resolution #1.   The part I dipped into concerning secular equations was quite clear. 

p. 907 — The power of theory !  The relative stability of Dewar benzene — trapped in a kinetic prison whose origin is orbital symmetry — it’s this sort of thing that makes the practical man (who has seen many theories come and go) sit up and take notice.  Dewar benzene was made in ’63 probably before the theories in this chapter were extant — was the relative stability a surprise?

The synthesis of Dewar benzene is given on p. 970 — giving a great proof of what photochemistry allows you to accomplish.

p. 910 — Nice to see the mechanism of action of the enediyne antibiotics. However, it isn’t clear (in this text) how they cleave DNA, although the diradical should be reactive as hell.  One mechanism I’ve read about is that they may remove hydrogen atoms from deoxy ribose in the DNA backbone (probably after intercalating with DNA).   More likely (to me) the diradical intercalates with the aromatic nitrogen bases of the DNA and raise hell with them. 

p. 924 — Nice to see a mechanism by which hydroperoxides form with a double bond present.  Quite important in biology.  All sorts of fatty acids in cellular membranes have cis double bonds (so they don’t pack well, which has the effect of liquifying the membrane).  The mechanism explains why these double bonds cause trouble.  The biophysics explains why they have to be where they are. 

End of Chapter — Despite all the cleverness expended on molecular orbitals where carbon is involved, there was nothing in this chapter concerning organometallics, which appear to have revolutionized synthetic organic chemistry in the past 50 years.   Look at Fig 12.17 p. 744 — allylic alkylation appears to involve a pericyclic reaction as do others. 

Anslyn pp. 807 – 876 (Chapter 14)

p. 807 “Most chemists think about bonding improperly”  — What an opening salvo for this Chapter — “Advanced Concepts in Electronic Structure Theory”.  I think A&D’s reasons for this are correct (at least for me).  They can be found on p. 813 (see the note) and p. 838 (ditto)

p. 808 — “These wavefunctions contain al the observable information about the system.”  — A huge assumption, and in fact a postulate of quantum mechanics.  OK, actually, since QM has never made an incorrect prediction. 

p. 809 — “In classical mechanics, the forces on a system create two kinds of energy — kinetic and potential”.  Hmm.  How does force ‘create’ energy?  It does so by doing work.  Work is force * distance, and if you do a dimensional analysis, you find that force * distance has the dimensions of kinetic energy (mass * velocity^2) — It’s worth working through this yourself, if you’ve been away from physics for a while.  Recall that potential energy is the general name for  energy which has to do with location relative to something else.

After reading Lawrence Krause’s biography of Feynmann (which goes much more into the actual physics than other biographies including Gleick’s), I cracked open the 3 volumes of the Feynmann lectures on physics and have begun reading.   It’s amazing how uncannily accurate his speculations were. particularly about things which weren’t known in the 60’s  but which are known now.  

       Feynman lists 9 types of energy (lecture 4 page 2)  
  l. gravitational (a type of potential energy)
  2. kinetic
  3. heat
  4. elastic
  5. electric
  6. chemical
  7. radiant (??)
  8. nuclear
  9. mass 

      He says that we really don’t know  what energy is (even though we know 9 forms in which it appears) just that it’s conserved.  Even so, the conservation law allows all sorts of physics problems to be solved.  To really get into why energy is conserved, you have to read about Noether’s theorem — which I’m about to do, using a book called “Emmy Noether’s Wonderful Theorem” by Dwight E. Neuenschwander.

      Later (Lecture 4 page 4) Feynmann defines potential energy as  the general name of energy which has to do with location relative to something else. 

p. 809 — The QM course I audited 2 years ago, noted that the Schrodinger equation really can’t be derived, but is used because it works. However,  the prof then proceeded to give us a nice pseudo-derivation based on the standard equation for a wave propagating in space and time, Einsteins E = h * nu, and De Broglie’s  p = h/lambda, and differenating the wave equation twice with respect to position, then twice with respect to time and equating what he got.   

However, to get the usual Hamiltonian, he had to arbitrarily throw in a term for potential energy (because it works).  

p. 810  “The energy E is simply a  number”  — should have said “The energy E is simply a real  number” which is exactly why the complex conjugate must be used.  If you really want to know what’s going on see — the 10 articles in the category == Linear Algebra Survival Guide for QM.

p. 811 – 812 — The qualitative discussion of the Laplacian is great — it also explains why higher frequency light has higher energy.  Worth the price of the book.  Localizing an electron increases its energy by the Heisenberg uncertainty principle, which was the reasoning I’d grown up with.  

One point for the unitiated (into the mysteries of quantum mechanics) to consider.  “The more nodes an orbital has, the higher is its energy.  Recall from Chapter 1 that nodes are points of zero electron density, where the wavefunction changes sign.”    Well, a point of zero electron density, or a point at which the wavefunction equals zero, means the electron is never (bold) found there.  So why is the probability of finding an electron on both sides of the node not zero.  You need to abandon the notion that an electron has a trajectory within an atom.  Having done so, what does angular momentum mean in quantum mechanics? 

p. 813 — Interesting that the electrostatic arguments for bonding (shielding nuclei frm each other, etc. etc. which I’ve heard a zillion times) are incorrect.  This probably explains the opening salvo of the chapter. (See also the note on p. 838).

p. 814 — “This is the fundamental reason that a bond forms; the kinetic energy of the electrons in the bonding region is lower than the kinetic energy of the electrons in isolated atomic orbits”  — this is because the wave function amplitude changes less between the nuclei.  However, since we’ve had to abandon the notion of a trajectory — what does kinetic energy actually mean in the quantum mechanical situation (see note on pp. 811 – 812).

p. 814 — “The greater the overlap between to orbitals the lower the kinetic energy”  — to really see this you have to look at figure 14.6 on p. 813 — The greater the overlap, the shallower the  depression of the wave function amplitude between the nuclei, which implies less change in amplitude with distance, whch implies a smaller Laplacian (a second derivative) and less kinetic energy for the electrons here.  So this is why overlapping atomic orbitals result in lower kinetic electron energy at sites of overlap    e. g. why bonds form (bold).  Great stuff ! ! ! !

      Continuing on, the next paragraph explains where Morse potentials (p. 422) come from, and why populating antisymmetric  orbitals causes repulsion (the change in orbital sign increases the Lagrangian greatly along with it the electron kinetic energy, despite the fact the the potential energy of the antisymmetric orbitals is favorable for keeping the atoms close — e.g. bonding).   

p. 815 — What does the Born Oppenheimer approximation (which keeps internuclear distances fixed) do to the calculation of vibrational energies — which depend on nuclear motion?    The way the energy of the solutions of the Schrodinger Equation using the BO approximation is gradually approached (moving the nuclei around and calculating energy) clearly won’t work for CnH2n+2 with n > 2. There will be more than a single minimum.  What about a small protein?   Clearly these situations the Born Oppenheimer approximation is hopeless.  Because of the difficulty in understanding A&Ds discussion of the secular equation (see comments on p. 828), I’ve taken to reading other books (which have the advantage of devoting hundreds of pages to A&Ds 60 to computational chemistry), notably  Cramer’s “Essentials of Computational Chemistry”  — He notes that lacking the Born Oppenheimer approximation, the concept of the potential energy surface vanishes.

p. 816 – 817 — Antisymmetric wave functions and Slater determinants are interesting ways to look at the Pauli exclusion principle.  The Slater determinant is basically a linear combination of orbitals — why is this allowed?  — because the orbitals are the solution of a differential equation, and the differential of a sum of functions is the same as the sum of differentials of the functions and orbitals are the solution to a differential equation.  

p. 823 — What’s a diffuse function?  Also polarization orbitals strike me as a gigantic kludge.  I suppose the proof of the pudding is in the prediction of energy levels, but there appear to be an awful lot of adjustible parameters lurking about.  

p. 824 — “the motions of the electrons are pairwise correlated to keep the electrons apart” — but electrons don’t really have trajectories — see note on pp. 811 – 812.  I got all this stuff from Mark P. Silverman “And Yet It Moves” Chapter 3

p. 824 — “the c(i)’s are incrementally changed until capital Psi approximates a correlated wavefunction.”  More kludges. 

p. 825 — Nice to see why electron correlation is required, if you want to study Van der Waals forces between molecules,  The correlation energy could be considered a intramolecular Van der Waals force.  

What is a single point energy? — I couldn’t find it in the index.

p. 826 — The descriptions of the successive kludges required for the ab initio approach to orbitals are rather depressing.  However, there’s no way around it.   You are basically trying to solve a many body problem when you solve the Schrodinger equation.  It’s time to remember what a former editor of Nature (John Gribbin) said “It’s important to appreciate, though, that the lack of solutions to the three-body problem is not caused by our human deficiencies as mathematicians; it is built into the laws of mathematics “

p. 828 — I was beginning not to take all this stuff seriously, until I found that the Hartree Fock approach produces results agreeing with experiment.  However, given the zillions of adjustable parameters involved in getting to any one energy, it better produce good results for n^2 molecules, where n is the number of adjustable parameters.   Fortunately, organic chemistry can provide well over n^2 molecules with n carbons and 2n+2 hydrogens. 

p. 828 — The discussion of secular determinants and the equations leading to them is opaque (to me).  So I had to look it up in another book “Essentials of Computational Chemistry” by Christopher J. Cramer (2nd Edition).  Clear as a bell (although, to be fair, I read it after slowly going through 20 pages of A&D), and done in 10+ pages (105 –> 115).

     Along these lines, how did the secular equation get its name.  Is there a religious equation? 

What can you do with an approximate wavefunction produced by any of these methods.  The discussion in A&D so far is all about energy levels.  However, unlike wavefunctions, operators on wavefunctions are completely known, so you can use them to calculate other properties (Cramer doesn’t give an example).  

     p. 830 – 831 — Even so, given the solutions of the secular equation for a very simple case, you see why the energy of a bonding orbital is less than two separate atomic orbital — call the amount B (for bonding). More importantly the energy of  the antibonding oribtal his greater than the two separate atomic orbitals by a greater amount than B — explaining why filling a both a bonding and the corresponding antibonding orbital results in repulsion.  This is rule #8 the rules of Qualitative Molecular Orbital theory (p. 28).

p. 834 — An acronym festival — CNDO, INDO, PNDO, MINDO 1- 3, AMI, PM3 etc.  at least they tell you that they aren’t much used any more.  

It’s amazing that Huckel theory works at all, ignoring as it does electron electron repulsion. 

p. 836 — If everything in Density Functional Theory (DFT) depends on the electron density — how do you ever find it?   Isn’t this what the wavefunctions which are the solutions to the Schrodinger equation actually are?  I’m missing something here and will have to dig into Cramer again. 

p. 838 — Most energy diagrams of molecular orbitals made from two identical atomic orbitals have the bonding and antibonding orbitals have them symmetrically disposed lower and higher than the atomic orbitals.  This is from use of the Huckel approximation, which simply ignores overlap integrals.  The truth is shown in the diagram on p. 831. 

p. 838 — Another statement worth the price of the book — the sigma amd pi orbitals are of opposite symmetry (different symmetry) and so the sigma and pi orbitals don’t mix.  The sigma electrons provide part of the potential field experienced by the pi electrons.  

p. 839 — Spectacular to see how well Huckel Molecular Orbital Theory works for fulvene — even if the bonding and antibonding orbitals are symmetrically disposed. 

p. 841 — Fig. 14.13 — I don’t understand what is going on in part B in the two diagrams where not all the atoms have an associated p orbital. 

p. 843 — With all these nice energy level diagrams, presumably spectroscopy has been able to determine the difference between them, and see how well the Huckel theory fits the pattern of energy levels (if not the absolute values). 

p. 846 — Table 1.1 should be table 1.4 (I think)

p. 849 — How in the world was the bridged [10] annulene made?

p. 853 — Why is planar tetracoordinate carbon a goal of physical organic chemistry?   The power of the molecular orbital approach is evident — put the C’s and H’s where you want in space, and watch what happens — sort of like making a chemical unicorn.  Why not methane with 3 hydrogens in an equilateral triangle, the carbon in the center of the triangular plane, and the fourth hydrogen perpendicular to the central carbon?   

Dilithiocycloproane has been made — presumably as a test bed for MO calculations, being able to predict something is always more convincing of a theory’s validity than justifying something you know to be true. 

p. 854 — What are the observations supporting the A < S ordering of molecular orbitals in 1, 4 dihydrobenzene?  The arguments to rationalize the unexpected strike me as talmudic, not that talmudic reasoning is bad, just that no one calls it scientific.

p. 856 — Good to see that one can calculate NMR chemical shifts using ab initio calculations (hopefully without tweaking parameters for each molecule).  Bad to see that it is too complicated to go into here.  More reading to do (next year) after Anslyn (probably Cramer), with a little help from two computational chemist friends.  

p. 858 — How in the world did anyone ever make Coates’ ion?  

p. 861 — Have the cyclobutanediyl and cyclpentanediyl radicals ever been made?

p. 863 — “Recall that the 3d orbitals are in the same row of the period(ic) table as the 4s and 4p orbitals’ — does anyone have an idea why this is so?  Given the periodic table, the 4s orbitals fill before the 3d, which fill before the 4p (lowest energy orbital fill first presumably).  The higher energy of the 4p than 3d may explain by d2sp3 orbitals are higher in energy than the leftover 3d orbitals — d(xy), d(yz) and d(zx).  Is this correct?  However the diagram in part B. of Figure 14.33 on p. 864 still shows that (n+1)s is of higher energy than nd, even though the periodic table would imply the opposite. 

       It’s not clear why the t(2g) combinations of d(xy), d(yz) and d(zx) orbitals don’t interact with the 6 ligand orbitals, since they are closer to them in energy.  Presumably the geometry is wrong?  Presumably d(z2) and d(x2 – y2) are used to hybridize with the p orbitals because they are oriented the same way, and d(xy), d(yz) and d(zx) are offset from the p orbitals by 45 degrees.  Is this correct? 

        This is the downside of self-study.  I’m sure a practicing transitional metal organic chemist could answer these questions quickly, but without these answers it’s back to the med school drill — that’s the way it is, and you’d best memorize it.

p. 865 — Frontier orbitals have only been defined for the Huckel approximation at this point — the index has them discussed in the next chapter.  On p. 888 they are defined as HOMO and LUMO which have been well defined previously. 

p. 866 — The isolobal work is fascinating, primarily because it allows you to predict (or at least rationalize) things.

This section does elaborate a bit on organometallic  bonding details, lacking in chapter 12.  However, no reactions are discussed, and electrons are not pushed.  Perhaps later in the book, but I doubt it.

It’s clear from reading chapter 12 that organometallics have revolutionized synthesis in the past 50 years. I’ll need to read further next year, in order to reach the goal of enjoying new and clever syntheses as they come out.

Does anyone out there have any thoughts about Cramer’s book? Any recommendations for other computational chemistry books? I’ve clearly got to go farther.

Merry Christmas and Happy New Year

Chemistry helps you understand group theory and not vice versa

Back in the day, we were told that group theory was important in quantum mechanics, because it simplified the Schrodinger equation, and ultimately the interpretation of spectra.  We really didn’t get into groups in the graduate QM course I took in ’61, but were told to look at Weyl’s book “The Theory of Groups and Quantum Mechanics” which didn’t get into representation theory until p. 120 after a lot of linear algebra and physics.  What chemist had the time? I didn’t.

In retirement, I’ve indulged my taste for math, and audited a graduate algebra course, which had a fair amount of group theory, but no representation theory.  In addition the instructor dumped all over chemistry and physics as part of his schtick of being a pure mathematician.  He avoided all applications to chemistry.  He did hold up for derision a book written by a chemist with several large groups explicitly written out.

So now that I’m reading chemistry again and am up to Ch. 14 of Anslyn and Dougherty  on computation of orbitals, I thought it was time to give group theory another shot.

The postulates of group theory really couldn’t be simpler, and as you delve into the subject, it’s amazing how much structure can arise from them.

Here they are.

A group is just a set G, which can be finite or infinite.  Chemical symmetry uses only finite sets, but in physics groups with an infinite number of elements are possible.

Just one operation is defined on G.  It is a binary operation, which is to say it takes any 2 elements of the group, and produces a third element of the group.  Examples include addition and multiplication, which take any two numbers and give you a third.    In mathematical terms, the operation is said to be closed.  Call the operation *.

* : G x G –> G ;

* : g *  h |–> i, where g, h and i are elements of G not necessarily distinct.

There is only one other requirement on the operation.  The operation must be associative — so that given 3 elements of the group, the order on which you subject them to the group operation doesn’t matter.  e.g.

a * (b * c) = (a * b) * c ; where you do the operation inside the parentheses first

The group must have one special element (usually called e for the German einheit meaning identity), but 1 will do.

For any element of a of the group 1 * a = a * 1 = 1

Lastly, every element of the group must have an inverse (written a’ ) such that

a * a’ = 1  and a’ * a = 1, so 1 is its own inverse, and other elements can be as well.

So the positive integers are NOT a group under addition (no inverse).  The integers are not a group under multiplication ( 0 has no inverse).

That’s all there is to it.  Yet the classification of all finite groups took 30 years, and 10,000 pages in journals, and people aren’t really sure they’ve got it done. The classification of the quasithin groups (don’t ask) was the subject of a 1221 page paper.

Representation theory is the correspondence of the elements of a group  to a set of matrices.  The group operation of a representation is always matrix multiplication.  You can find a gentle introduction to matrices in the 9 posts  in the category —

The math books don’t have any chemistry, and while groups are worth studying for their own sweet selves, I want to see what they offer the chemist (well, more realistically- HOW they offer what they do to the chemist).  So I’ve begun reading “Molecular Symmetry” by D. J. Willock.  Lots of chemical structures, schematic diagrams (some not particularly intuitive), and an approach to groups through symmetry.

What is really exciting about all this, is that chemistry lets you explore the structure of groups by moving a molecule around so that it superimposes on itself.  The book shows how the set of symmetry operations you can perform on a molecule form the elements of a group (showing that the elements of a group aren’t limited to just numbers).   The group operation is simply doing one symmetry operation after another. So instead of screwing around with matrices, which have no visual content (although their effects do), you can play around with simple molecules like water, ammonia, benzene and watch a group in action.

Technically what you are really doing when you do this is looking at what is called a group action — the action of a group on another set (e.g. the distribution of a collection of atoms in space in this case).  But, to my mind it’s really a way (and a better one) of representing a group.  Water is an example of the Viergruppe (4 group), which has only 4 elements.  The instructor said it’s a very strange group.

Parenthetically it is worth noting that Slater (of the Slater orbitals, and Slater determinant of quantum mechanics) hated groups — calling them the gruppenpest.  Anslyn has a lot about both in  pp. 817 – 822.

It’s too early to fully recommend the book, but the first 50 pages are quite fine.  Stay tuned

Anslyn pp. 753 – 806

p. 755 — Interesting how differently medicine characterizes value distributions.  Consider one distribution of polymer weights given here — 10, 10, 10, 10, 10, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000.  Medicine is interested in 15,000 which one might call the median weight.  Translate this into cancer survival, with a more reasonable distribution of numbers say 3, 10, 12, 13, 13, 14, 16, 20, 25, 36, 60.  The median suvival in months is what medicine (and patients) want to know.   The outliers of 3, 60 screw up the average, but roughly half of patients will live less than 14 months and half live more — with one or two lucky ones living 3 or more years.  Patients also want to know about the longest survivors, because it might be them.  Patients with amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) are always told about Stephen Hawking, who has lived nearly 5 decades rather than 5 years with the disorder. 

p. 756 — I suppose there wasn’t time or space to chemically describe just what a leucine zipper actually is, but it’s a beautiful thing, and the hydrocarbon side chain of leucine (CH2-CH- (CH3)2) is the tooth of the zipper.  For a picture see    Leucine zippers are common in proteins binding DNA, and zips them together allowing combinatorial binding of adjacent DNA sequences.  

p. 757 — Poor explanation of gel permeation chromatography (GPC).  Polymers of a size fitting into the pore size of the column spend more time in the column and are eluted last.  Not explained is how larger polymers get through the column at all.  They get through because the column is packed with beads with pores of a certain size.  Polymers not entering the pores of the beads, flow around (italics) the beads and are eluted faster.  

p. 763 –>  The stuff on dendrimers is interesting, particularly the two ways of making them and the interior holes they contain.  People are trying to find uses for them in drug delivery, particularly against cancer. You can link multiple copies of a drug to the outside of a dendrimer if the periphery is of the correct chemistry (this is polyvalency, a term from immunology).  This is important particularly for work involving the immune system as all antibodies are polyvalent. 

p. 775 — Nice to see how derivatives of buckyballs are made.  I wouldn’t have thought that Diels Alder would work with C60, as it seems so complete.  The disparity in lengths between the 6 – 6 bonds (at 1.38 Angstroms nearly the classic 1.34 of ethylene and still close to that of benzene at 1.40) and 6 – 5 bonds (1.45 — nearly the classic 1.54 for an sp3 – sp3 carbon carbon bond).  Do the ring currents on one side of the buckyball cancel those on the other.  

p. 776 — (n/2 – 10) should be (n/2) – 10

p. 778 — Any idea why SH is attraced to gold (as opposed to OH, NH, CH, PH, SiH)?  Clearly true as in OH (CH2)n SH, only the SH bonds to gold. 

p. 778 – 779 — An opportunity was missed to show how putting a small hole in the class slide allows you to form a lipid bilayer (exactly two lipid layers thick), and use it to study permeability, ion transfer, etc. etc. 

p. 792 — Why not just give the O-H bond strength (119 kiloCalories/mole) instead of saying that it’s very strong? 

p. 796 — What is methyaluminoxane ?

p. 799 — Group transfer polymerization is truly beautiful chemistry.   How did Webster ever find it?

The big enchilada chapter is coming up, and is the reason I’ve read the book sequentially so far.  Hopefully I’ll understand sophisticated molecular orbital theory \ along with molecular dynamics, and most importantly,  the limitations of both after I’ve read it.  I’ve never trusted molecular dynamics simulations of proteins, membranes, ion channels  etc. etc., not because I think their wrong, but because of the possibility of tweaking parameters to get what you want.   Hopefully the next chapter will give me the chops to read books on computational organic chemistry, articles on protein folding.  A big order but A&D have been great so far.

Anslyn pp. 705 – 752

The chapter on organometallic chemistry is the only chapter of Anslyn and Dougherty so far that I’ve found disappointing. Perhaps because it’s the subject I’ve known the least about, and needed the greatest help.  However, It leaves out a lot of basic explanations (if such exist).  For more detailed whining see although there is plenty in this post.

p. 707 — I’ve never understood why the 4s energy level is lower than the 3d, or the 5s than the 4d etc. etc.  Any explanations out there? 

p. 707 In the CH3Mn(CO)5 compound CH3 is said to give 7 electrons, when in fact it is giving 1.

p. 709 — Can more than 1 dz2-like orbital be formed?  Interesting that it can be formed along any axis.  

p. 710  — “All metals have characteristic oxidation states” . . . . ” We do not discuss in length, the origin of these oxidation states.”  Well, why not?  What is physical organic chemistry for?  This makes their discussion of organotransition chemistry seem like medical school — we don’t know why it is the way it is just suck it up and memorize.  The ability to explain things from a few fairly simple principles is one of the reasons I love organic chemistry (along with its great diversity of molecules).  It would be great to know why and how Fe likes to sit inside a porphyrin ring in hemoglobin and why it binds oxygen and carbon monoxide.  Apparently this book has no intention of telling you. 

p. 711 “These subtle deviations from standard geometries (trigonal bipyramid, octahedral, tetrahedral, square planar, square pyramidal) are not dominant factors influencing reactivity”  Why aren’t they?  Altering carbon carbon geometry certainaly alters reactivity.  The book is silent.  It seems to me this is something a physical organic chemistry textbook should tell you.


p. 712 — Why an orbital should be raised in energy if it lies along the bond to a ligand to a metal is unclear and actually counter intuitive — in carbon chemistry, good orbital overlap lowers the energy of the molecule.  I looked crystal field theory up in Crabtree — ligands are considered as having negative charge, and this would raise the energy of a filled d orbital — but what if the orbital is empty?

p. 714 — Stabilized cyclobutadiene — wow !  When did this happen.  Are the CC bonds of the cyclobutadiene inthe Fe(CO)3 complex all the same length? 

p. 715 — Any ideas as to why Mg, Zn, Zr, Sn, B, Al, Li are the elements involved in transmetallation?  Interestingly only Zn, and Zr are actually transition metals.  Seems like its back to med school — see above. 

p. 715 — The definition of metathesis  “the pair wise interchange of two ends of two bonds” is nearly incomprehensible as is the example.   The later discussion of metathesis is too brief to be helpful.

p. 719 — A diagram with d orbitals in it at last.  Everything so far (and up to p. 745) is just lines between metal and ligand.  Not terribly informative. 

p. 721 — A great example of a reaction impossible in ‘classic’ organic chemistry (I think), oxidative insertion of a metal, resulting in its insertion in a sp2 hybridized carbon – halogen bond.  Impressivo.   

p. 723 — The Hartwig catalyst for C-H activation looks like a dog’s breakfast of components.  It’s an ugly asymmetric Rube Goldberg sort of molecule.  How in the world did they ever find it?  

p. 735 and previous — The number of essentially new transformations permitted by organometallics is incredible — and is probably equal to the number of named reactions in the field when I left it in ’62.  I wonder what percentage of synthetic steps in the latest and greatest syntheses involve metallo-organics.   The 7 reactions on p. 735 are particularly impressive. 

p. 735  — Why is the metal an electron sink?  Easy to see if it is in a positive oxidation state, but if neutral, the electronegativity of all (italics) the transition metals are at least .5 units LESS than carbon (at 2.5)

p. 738 — Wikipedia says that the Monsanto acetic acid synthesis was developed by BASF in 1960.  Interesting, that it wasn’t being mentioned in grad school back then.  

p. 742 — Interesting that 4/6 of the Palladium coupling reactions have Japanese names attached to them — Suzuki, Sonagashira, Negishi and Kumata — any idea why?  Is there a Japanese grandfather organometallic chemist giving rise to them?   From looking at their diversity, it’s obvious that these reactions have transformed organic synthesis, but now is not the time to get into them. 

Why Palladium and not some other transition metal?  Is there something about its electronic structure and atomic radius?  Anslyn is silent.  Were others tried?   Would others work as well?  If not, why not?

Clayden et. al. spent a lot of time on enolate anions and their use in synthesis in the first edition of their book (2001).  The new edition will be out next year (personal communication).  It will be interesting to see if more attention is paid to organometallics in synthesis, and in general, in that book.  However (p.744) enolate anions are used in allylic alkylation.  Looks like a whole new world to explore. 

p. 744 –>  The parts on olefin metathesis were too dense, and I’ll have to delve into this at a later date. 

I’m going to try to finish Anslyn by year’s end, so I’ll get back to this organometallic chemisty later.  I’m disappointed that the chapter didn’t give me a better theoretical background on why organometallic reactions occur. 

I did get two books out of a local college library — “Molecular Chemistry of the Transition Elements” by Mathey and Sevin and “Organotransition Metal Chemistry” by A. F. Hill.   The Hartwig book is signed out to one of the profs.  Any thoughts on any of them?  

Happy Thanksgiving to all ! ! !

For why we should all be thankful every day see —



Disappointed with Anslyn’s Chapter 12 on Organometallics and a request for help

I had really looked forward to this chapter as organometallic chemistry has exploded since I left the field in ’62.  The explanation of the basics of the bonds formed between the metal and the organic substituents seem rather skimpy and at odds with much of the preceding 704 pages.  Instead of orbital drawings, there are lines drawn between atoms, something typical of English and Cassidy’s book (copyright 1956) which we used as undergraduates in ’58.  I had looked forward to seeing d-orbitals (or hybridizations of them with s and p orbitals) in action, with electrons swooping like swallows between them as they changed, similar to earlier diagrams.

D orbitals are a form of the spherical harmonics for angular momentum with quantum # 2.  The 5 of them aren’t even shown in this chapter, just a referral back to Figure 1.26 on p. 60.  If they are hybridized with s and p orbitals the results aren’t drawn (as they are over and over for sp1, sp2 and sp3).  Why not?  Too are they hard to draw? Don’t we know what such orbitals look like?

Then on p. 712 d orbital energy level splitting is introduced.  Crystal field theory is mentioned,  said to predict the splitting, but not further discussed.  A referral to ‘a text book focused on organic or organometallic chemistry’ is advised.  Well, I never studied the stuff, so I tried to look it up in Cotton’s “Advanced Inorganic Chemistry” — nothing in there, surprisingly, even under ligand field theory.  I decided to plunge ahead, even though I never like to read past something unclear to me (in chemistry at least.  In mathematics, it happens all the time).

It was the next statement that totally blew me away:  “Suffice it to say, a general rule for predicting the splitting is that d orbitals that lie along the bonds are raised  in energy”.   Hello?  Everything up to now has implied that orbital overlap is a good thing and lowers molecular energy — remember strain energy.

So it was definitely time to read about crystal field theory.  The first thing I read was pp. 288 -293 of Berry’s PChem book, “Electronic Structure of Complexes”.  The description of crystal field theory (developed for crystals, hence the name) was quite clear.  It starts from the distribution of ions in space (never mind how they got there).  This is strikingly reminiscent of VSEPR (Valence Shell Electron Pair Repulsion).

As they note, an atom by itself with its electrons is inherently spherically symmetrical.  Only the orbitals with an angular momentum (e.g. everything other than an s orbital) will be affected by the disposition of ions around the central atom.  Even if we have as symmetric a disposition of surrounding ions as we can get, the electric field they set up is not the same in all directions (e.g. not spherically symmetric), so orbitals with angular momentum will be affected by the field.

A bit of thought shows you that if you want to put 4 negative charges an equal distance from a central positive charge, and put all 4 as far away from each other that they can get (e. g. on the surface of a sphere), you wind up with a tetrahedron.  Similarly, 6 negative charges, given the same constraints, produce an octahedron.

So if we have the positive metal nucleus surrounded by negative ions, the filled orbitals of the metal pointing toward the ions will experience repulsion by the electrons of the ions, raising their energy. Orbitals not pointing this way will be unchanged.   This I understand clearly, and it’s how previously energetically identical orbitals (say px, py and pz) are split into orbitals of different energies.   But what holds things together in this situation?  Where’s the bonding?  I was taught to think orbital overlap is a good thing.

The discussion on p. 290 shows that (if you shut your eyes and somehow pretend that bonding is still present) in an octahedral complex dz2 and dx2-y2 will be raised in energy, while dxy, dyz, and dxz will be lowered. Similarly in a tetrahedral field exactly the opposite occurred.   This is quite clear when you look at the pictures.

Then on p. 292 — the denouement.  How bonding actually occurs.  It’s covalent, and somehow molecular orbitals make everything OK.  No pictures are given.  All valence shell orbitals of the metal (s, p, d) and the ligands are used in their construction.

Perhaps bonding doesn’t matter.  Somewhere it is said that the organic ligands in transition metal complexes act differently, with unstable ligands (like carbenes) being stabilized and stable ones (like C-H bonds) labilized.  Maybe the central metal atom acts like the alcohol used by pimply adolescents everywhere, trying to get their date a little high and doing things they ordinarily wouldn’t.

Any help the cognoscenti out there can give will be appreciated.  I plan to look at a variety of books on the subject — Crabtree, Hegedus, Mathey and Hill, which I’ve checked out of the local college library.  Unfortunately, what appears to be the latest and greatest, Hartwig has been checked out, so I may have to buy it.

This post is going to be work in progress, with more added (and dated) as clarity (hopefully) emerges.  Now back to chapter 12 of Anslyn and Dougherty.

Anslyn pp. 627 – 703

Great chapter, but why would a nascent organic chemist go into physical organic chemistry?  I’m sure there are I’s to be dotted and T’s to be crossed, but most people going into any branch of science want to find something new and exciting.  Even A&D admit this in the chapter’s last paragraph “it seems unlikely that fundamentally new mechanistic pathways for organic molecules will emerge”.  True enough, but new reactions always will always be found, and you need to know this stuff to figure out what is really going on.  

P. 631 — I don’t think LTMP is actually shown in the ‘Going Deeper’ side bar. 

p. 633 — The explanation of the mostly trans product in 4 tBu cyclohexanone seems fishy as it totally ignores the steric hindrance of the tBu group.   

p. 634 — Nice to have the value in kCal/mole for allylic strain (3 – 4), but it should have been given when first discussed on p. 100.  The value for diaxial strain is also given — I’m sure this was discussed earlier but it isn’t in the index.

p. 639 — The explanation of the common ion effect is confusing. 

p. 647 — When starting to read about a solvent separated ion pair, I wondered how anyone would find independent evidence of it.  The way they did it was clever.  The concept probably has great relevance to membrane biology, as all phospholipids have a negative charge facing the liquid bathing them.  Are ions bound directly to them or separated by solvents?  Chemistry becomes particularly tricky at interfaces — but this is exactly where this sort of thinking is needed.   I see Winstein cited here — this is why Schleyer called him Solvolysis Sol. 

p. 657 — The rapid equilibration of the cyclopentenyl cation even at -139C is fascinating, and something I wouldn’t have predicted.  Maybe chemical bonding is more fluid than I would have supposed. 

p. 661 -> 664 — Fascinating to see the ‘answer’ to the questions about classical and nonclassical norbornyl cations that so exercised Schleyer and many other chemists back in the late 50’s and early 60’s.  Stable ion media and solid state NMR (both unknown at the time) did the trick.  Not finding distinct NMR structures at 5 degrees KELVIN is good enough evidence (for me) that nonclasical norbornyl cations exist.  Also if the barrier to interconversion of 2 norbornyl cations is under .2 kiloCalories/mole, this makes the controversy essentially irrelevant at room temperature and above, where the average thermal energy/molecule is .6 kiloCalories/mole.  Even if two forms actually exist, it’s got to be like keto-enol tautomerism.  A fascinating conclusion to the controversy. 

p. 666 — The dodecaboranes and the carboranes are fascinating.  Lipscomb was starting to work on them when I was in chemistry — most of the attention was paid to the (until then) wierd bonding in B2H6. 

p. 673 —  “Termination usually involves the formation of a tetroxide”  — four oxygens in a row — wow !  Why not 6, 8 or more?  What is the evidence for tetroxides?

p. 681 — Interesting to know that oxime isomers can stably exist as E and Z.  I wouldn’t have thought so. 

p. 684 — Why would Breslow want to functionalize the methyl group (carbon # 18) between the 6 and 5 membered rings of the steroid nucleus?   Because it is functionalized (a CHO group)  in aldosterone, a steroid hormone vitally involved in maintaining blood pressure.  Aldosterone is made by the adrenals, and people deficient in adrenal function have low blood pressure, while those with NO adrenal function at all die of shock when stressed in any way.  Hydrolysis of the oxime shown would produce a C18 aldehyde.

p. 688 — What is sensitized photolysis? Explained on p. 957 but there should be some link to it here.   Also what is a triplet manifold?

 Not that it hasn’t been interesting so far to see where things have gone, but transition metal organic chemistry, photochemistry and quantum mechanical calculations were barely getting started in the early 60s.  The remainder of the book is likely to be quite new and unfamiliar, and we’ll see if I’m able to understand and retain.   Always good to try and learn with a bit of anxiety on board (e.g. am I smart enough to learn this stuff?).  Stay tuned.