I Remember Primary Kinetic Isotope Effects[1]

I’m not that good at primary and secondary kinetic isotope effects, so I thought I’d review and refresh. If you click on the I remember Clifford youtube link, you can study in style!

Chances are that you might want to review this stuff too, since I know my memory is spectacularly bad with physical organic chemistry.

Kinetic Isotope Effects (KIEs) are good indicators of the mechanism of a reaction. First we exchange a hydrogen for a deuterium in a compound. If the H/D bond is broken in the rate determining step, this is called a primary KIE. We compare the relative rates of reaction to establish a quantitative (numerical) basis for understanding how different the rate of reaction with hydrogen (k h) is with the rate of reaction with deuterium ( k d).

The upshot of all this is the C-D bond has a greater activation energy than the C-H bond. The C-D bond is stronger[2], with a lower zero-point energy (ZPE) than a C-H bond, however their differences in energy disappear at the transition state.

In short, it’s much easier to remove a H than a D, which explains why primary KIEs are usually above 2. The one in the illustration is probably about 5. If the primary KIE is relatively low (i.e. 2), then the transition state (TS) looks like either the product or reactant. If the primary KIE is high (i.e. 6), then the TS involves significant bonding between the hydrogen and both the old and new binding atoms.

Yeah that’s all the brain power I have tonight… more tomorrow!

[1] Also, I Remember Clifford and I’ll Remember April. oh zeh Jazz Muse ik!

[2] This is due to several factors. First, the vibrations associated with a C-D bond contribute less to the zero-point energy (ZPE) than the vibrations from a C-H bond, which makes a lower ZPE. (I don’t really understand this?) help

“I am a major shoe queen.”

You wouldn’t necessarily expect that from a quote that has been attributed to Gov. Arnold Schwartzenegger, but there it is. A little honesty shows how much male fashion has changed. Not vanity, mind you, just a guy who appreciates that any outfit or look can be ruined by the wrong choice of footwear (think suits and sneakers together, unless you’re fighting cancer). Style is certainly subjective, however, and luckily the only person you have to please is yourself.

My purchases in this department had tended to be running shoes for most casual occasions, with white socks. *cringe* And you wouldn’t necessarily except much more from me – chemists are not known for their except fashion sense, like say, most of the rest of the educated world is. Now that I actually make a salary of sorts, I have the time and money to improve my shoe collection. Even though I didn’t go see Sex and the City, I wonder if subconciously I am channeling the same goals if not the same élan. To illustrate, I would like to take a moment to chronicle some of my fashion blunders. (in hindsight, I could have done worse.)

• White socks with loafers
• buzz cut
• dirty old tennis shoes
• pleated pants
• t-shirts with beer logos
• trucker hats
• tight tight jeans
• those really annoying shorts with little animals sewn in. glad I tossed that one!

Yeah. Ouch. Cleaning wardrobe shouldn’t be this hard. Gotta go shopping again sometime soon! Peace

Ode to the Joy of Electrophilic Bromination

I think it’s strange that my favorite Beethoven symphony (Number 9, Number 9… ) is played around Christmastime. Additionally, this may not seem a propitious place from which to launch into a discussion of enzymatic bromination. And you would be right. Except that in both cases, I don’t really know what’s going on. Ode to Joy isn’t really religious and has nothing to do with snowmen or chestnuts or open fires. (Plus I don’t speak German. But I do hear that the translation is festive!)

In a similar way, we scientist types have only guesses as to how enzymes perform brominations. We think haloperoxidases mostly involve vague electron-pushing around peroxides, bromine anions, and metals (Fe or Mn) to make hypohalous acids, but beyond that… well… we dunno.

And uh I quote:

“Although a large number of halogenated organic compounds have been isolated, not much is known about the mechanisms by which fluorine, chlorine, bromine, or iodine atoms are incorporated into organic compounds.” [1]

Regardless of whether that was a horrible analogy, we do know much about electrophilic bromination in other contexts. For example, standard bromination conditions in organic chemistry commonly use NBS or bromine, and their mechanisms are well understood (think like Sophomore Organic Reactions) level of understanding). Hopefully someone can fill in the blanks someday with enzymatic halogenation. Although, it might be possible an understanding of Fenton chemistry would help… hmm. I’m certainly not an expert in this field, but I’d love to hear from someone who is!

[1] van Pee, K.-H.; Unversucht, S. Chemosphere 2003, 52, 299–312.

Biosynthesis of Terpenes

Molecules have a beauty and simplicity and belies their importance and efficacy. My inspiration in chemistry was reading the aptly named Atkins tome Molecules, a book that fascinated me to no end. Really, ad infinitum.

Life begins with geranyl diphosphate. “O-P-P!” as I say it. To get most of the essential oils, some oxidation or rearrangement needed. btw, not all arrows were created equal.

The really interesting part is that the selective oxidation is something that chemists can do, we don’t have to rely on magic enzymes (they’re really not that magical – just have about a billion years of evolution more expertise. same difference). As a practical matter, chemists are mostly concerned with chemoselective oxidation to do this.. Hydrocobaltalation of myrcene, followed by exposure to heat and triplet oxygen can give linalool peroxide, which can then be reduced to linalool. Old school reference! I hope there are easier ways to do this chemistry. Racemic product by the way!

Next time: electrophilic bromination!

Ferris Bueller’s Day Off

Welcome! I am writing this blog as a creative, mostly harmless addition to teh interwebz. I will traverse the realms of organic chemistry for my own edification and the belief that others will want to listen (also a belief in instant fame never hurts!) And, as my hero Bueller sagely said, “Besides, how could I possibly be expected to handle school on a day like this?!”

A bit about the appellation: Linalool, like most acyclic terpenes, is harvested from natural sources, as well as produced commercially. The biosynthesis is certainly straightforward, since practically all the terpenes, and it seems, a ridiculous number of biomolecules, are made from geranyl pyrophosphate. Ah, monoterpene synthases are ubiquitious, and linalool is but a drop in the acyclic terpene ocean, and as cool as the name may sound, there are lots to choose from in this group!

Similarly, the uniqueness of the name is outshone by the usefulness of the compound. As all chemicals go, the dosage can indicate the use. Linalool is found in pesticides, perfumes, and cigarettes, and the concentrations fall correspondingly from almost 90% to 5% to 5ppm. It seems nowadays practically everything can found at the 5 ppm level. Just look at the levels of cocaine in paper money – and somehow we humans survive still. Quantity is usually key to toxicity, except for maitotoxin – run away!

I suppose the bottom line is that linalool provides some fresh scents with a little bit of spice. I’ll try to  live up to that!

Oh, and here’s the my cat loves total synthesis photo! I don’t think he knows how to laugh out loud, sorry

my cat totally synthetic