Dipole and size of a thioether relative to hydrocarbon I am an enzymologist and I would like to check whether the consensus of how enzymes tell thioethers from hydrocarbons on substrates is a fact or fiction.
So are any of these wrong?


S–&pi; interactions are the sole discriminant (in enzymes at least)
They have the same dipole
They are the same size
A thioether and a hydrocarbon have the same angle


From what I can tell...
Point #1 is not really in question: even if it does not account for much, aromatic residues are often found with thiols and thioethers (1/3 of protein have a methione involved in a S–&pi; interaction).
From what I can tell of point #2, 3.55 vs. 3.58 units in electronegativity (ref. wikipedia: electronegativity) won't make a difference. From point #3, while, yes, sulfide is 360 pm and methane is 380 pm (ref. wikipedia: kinetic diameter), but the former is R-S-R, R-CH2-R, so it might be different.

I am not saying they are very different: thialysine (thioether) is a toxic analog of lysine (alkane) and norleucine (alkane) of methionine (thioether; toxic for SAM usage only) due this reason. But nature has evolved to discern similar compounds.

An example, cystathionine (pictured below) is a thioether of cysteine + homoserine or homocysteine + serine (both routes exist) and one enzyme (cystathionine beta-lyase, C&beta;L) can bind the amine on the shorter side, deprotonate the &alpha;-carbon and eliminate the thiol (homocysteine) and release the imine (hydrolysed to pyruvate), while a different enzyme (cystathione gamma-lyase, C&gamma;L) acts on the other (cysteine and ketobutyrate). The two enzymes do not catalyse both reacts as it would be wasteful (not much just a ATP>AMP). The evolution from one to the other has not be published, but from what I can tell S–&pi; interaction is the driving force. AFAIK, the closest literature to this on cystathionine elimination is my own paper, so I know there is no answer there.
I just realised that I got the dipole business utterly wrong as sulfur has two lone pairs.
I checked dimethyl sulfide, propane and dimethyl ether and was surprised how differently they behaved. The former has a total dipole moment of 1.5 D ref, while the second near zero (0.1 D) as expected from a non-polar molecule, while the last has 1.3 D.
Whereas there is only a 0.03 difference in electronegativity between C and S (vs. .89), the geometry is different, which I did not know about. Wikipedia on says:


thioether article: "C–S–C angle approaching 90°. The C–S bonds are about 180 pm."
ether article: "C–O–C linkage defined by a bond angle of about 110° and C–O distances of about 140 pm".
alkane article: "154 [pm] for a C–C bond [and] with an angle of 109.47° between them."


So the side chain of methionine should actually be able to hydrogen bond with stuff (not electrostatically, but dispersively). So I was surprised to find papers I had not found prior (ex1, ex2).

S-&pi; are probably the strongest force nevertheless (the bond has an enthalpy of 2.6, 1.1 or 0.7 kcal mol-1 depending on the angleref, which is comparable to N−H···:O hydrogen bond (1.9 kcal mol-1))