Compare this to the case of SM33 in figure . In water, the local density in the first solvation shell is largest for the sulfide (ring) S, closely followed by the sulfone S, and then the amine N is noticeably lower. In all cases the local density is lower than we found for SM36. Considering next the case of neat 1-octanol, we again find that the local density in the first solvation shell around the solute amine N and sulfone S are all greater than bulk, with the largest density around N, followed by sulfone S. The values are similar to those observed in neat 1-octanol for SM36. However, this is not the case for the sulfide (ring) S. The local density in the first solvation shell is very small and less than bulk. Moreover, we find that with the addition of water, in water-saturated 1-octanol, the change in local density in the first solvation shell is insignificant, and noticeably the local density around the sulfide (ring) S remains very small. In summary, for the case of SM36 where we observe the largest increase between log 10 P o * /w 1 and log 10 P o/w 1 , we observe a large increase in the local density of solvent O in the first solvation shell around the sulfoxide (ring) S and sulfone S in going from neat to water-saturated 1-octanol. On the other hand, for the case of SM33 where we observe the largest decrease between log 10 P o * /w 1 and log 10 P o/w 1 , we observe that there is very little change in the local density of solvent O in the first solvation shell around the sulfide (ring) S and sulfone S in going from neat to water-saturated 1octanol, and moreover that the local density around the sulfide (ring) S is very small. In figures S1 and S2 of the Supporting Information we provide spatial distribution functions (SDFs) for SM33 and SM36, respectively, in neat 1-octanol. We see the absence of the 1-octanol O near the (ring) sulfide S in SM33. In figures S3 and S4 of the Supporting Information we provide a snapshot of the system for SM33 and SM36, respectively, in neat 1-octanol. The snapshot likewise demonstrates the absence of the 1-octanol O near the (ring) sulfide S in SM33.