setting aside the regulatory challenge here (deuterated caffeine probably won't kill you at this quantity, but the biological effect of deuterium is generally negative https://en.wikipedia.org/wiki/Heavy_water#Effect_on_biological_systems), the more practical roadblock is that deuterated caffeine costs thousands of dollars per gram (https://www.sigmaaldrich.com/US/en/product/aldrich/725625). even assuming generous economies of scale, a typical cup of coffee contains ~100 mg of caffeine, which which is easily over $100 of caffeine-d9 at current market pricing.

perhaps there is some market for people with more money than sense that are willing to pay hundreds of dollars for a cup of coffee with an unclear long-term health risk profile and a ~40% better pharmacokinetic profile (wall street, maybe? somewhere in SF?) but imho at that point why would you not just snort a line of coke?

@pyrylium Interestingly, In D9-deuterated caffeine, the mass fraction of deuterium is 9%. So 9 mg in a cup of coffee. A litre of tap water contains 35-70mg of deuterium, so the amount of deuterium the deuterated caffeine is comparable to that in the water you dissolve the coffee in, and very small relative to that in daily water intake.

@pyrylium I think a more relevant comparison is with the cost of a deuterium source such as https://www.sigmaaldrich.com/SE/en/product/aldrich/176036 which in any case is much higher than wholesale prices. I guess the orderable d9-caffeine is hand made in scarce quantities, apples to oranges to compare it with a potential industrial process.

The synthesis can be quite straightforward, e.g. https://www.thieme-connect.com/products/ejournals/pdf/10.1055/a-1972-3819.pdf

(and now after looking it up I want to go back to doing some organic chemistry)

@lukres good to finally see another chemist on here. I agree that caffeine deuteration is not a particularly complex synthesis, but technoeconomic evaluation of the cost of wholesale caffeine-d9 by simple deuterium mass balance elides the (nontrivial!) costs of skilled labor and equipment necessary for a trained synthetic chemist to perform the deuteration -- which, involving the substitution of non-labile hydrogens, is not a simple dump-and-stir. the prep you reference starts from xanthine (cheap but not free), has an 80-90% yield at the one-gram scale, and requires a biphasic extraction in DCM followed by vacuum filtration and recrystallization. any skilled process chemist will attest that these unit operations comprise a synthesis of the sort that will likely not scale seamlessly to kilogram+ scale. the process utilizes pyrophoric sodium hydride and acutely toxic methyl iodide, which present safety considerations for a commercial bulk synthesis. finally, producing a food-grade additive will entail even further purifications and instrumental analysis of the final product -- wouldn't want any DCM to end up in your coffee!

it is from the sum total of all these considerations that we can expect the price of caffeine-d9 on a per-deuterium basis to be substantially elevated from simple precursors like CD3I. it's true that on an absolute abundance basis, deuterium is actually quite common. however, as with all isotope chemistry, it's the relative abundance that counts.

@pyrylium I read the wiki article you linked, it suggested that it's very hard for humans to consume enough heavy water to come to harm, but it's a little uncertain without much evidence.

It also mentioned something interesting about more cheaply producing deuterated larger molecules. By bootstrapping - raising a prokaryote that can tolerate fully deuterated water, which builds glucose etc with all deuterium, which can then be metabolised by more complex deuterium-tolerant organisms, etc. With lots of work maybe whole pathways to complex molecules could be designed using this.