Kinetic isotope effects (KIE) are a valuable tool for probing mechanisms without changing the potential energy surface. Their interpretation can sometimes be difficult – for example is a perdeutero group larger or smaller than the perhydro analogue?

O’Leary, Rablen and Meyer have examined two related molecules and their KIEs relating to stereoinversion.1 1 exhibits a normal isotope effect (kH/kD = 1.06) while 2 has an inverse isotope effect (kH/kD = 0.880). They optimized the structures and transition states (see Figure 1) for racemization of both compounds at B3LYP and MP2, and computed isotope effects based on the Biegeleisen-Mayer equation (which is based on reduced partition functions). The KIEs obtained from the two computational methods is very similar.


d8–1


d4–2: X=D, Y=H
d6–2: X=H, Y=D
d10–2: X=Y=D

1

1TS

2

2TS

Figure 1. MP2/6-31G(d,p) optimized geometries of 1 and 2 and the transition states for their racemization.

The experimental and computed KIEs are listed in Table 1. The agreement between experiment and computation is excellent – suggesting that computations should be routinely employed when analyzing isotope effects.

Table 1. Experimental and computed KIEs for racemization of 1 and 2.

 

Expt

Comp

d8–1

1.06

1.075

d6–2

0.880

0.888

d4–2

0.952

0.953

d10–2

0.847

0.846

The authors decompose the isotope effects into enthalpic and entropic components and note that the interplay between these two can be subtle – sometimes one might dominate and other times the second term will dominate, and the terms can be cooperative or non-cooperative.

References

(1) O’Leary, D. J.; Rablen, P. R.; Meyer, M. P., "On the Origin of Conformational Kinetic Isotope Effects," Angew. Chem. Int. Ed., 2011, 50, 2564-2567, DOI: 10.1002/anie.201007322

InChIs

1: InChI=1/C18H14O2/c19-15-7-11-3-1-4-12-8-16(20)10-14-6-2-5-13(9-15)18(14)17(11)12/h1-6H,7-10H2
InChIKey=DYZSIUYFWKNLHS-UHFFFAOYAB

d8–1: InChI=1/C18H14O2/c19-15-7-11-3-1-4-12-8-16(20)10-14-6-2-5-13(9-15)18(14)17(11)12/h1-6H,7-10H2/i7D2,8D2,9D2,10D2
InChIKey=DYZSIUYFWKNLHS-UFBJYANTEO

2: InChI=1/C16H18/c1-11-5-3-7-13-9-10-14-8-4-6-12(2)16(14)15(11)13/h3-8,13,15H,9-10H2,1-2H3
InChIKey=OBRIKDRTDGHGIQ-UHFFFAOYAU