ro les .) ▁ ▁The ▁difference ▁in ▁the ▁length ▁of ▁the ▁ben zo y lo xy ▁and ▁the ▁phen yl ▁link age ▁contrast ed ▁between ▁c oca ine ▁and ▁ph eny lt rop anes ▁makes ▁for ▁a ▁shorter ▁distance ▁between ▁the ▁cent roid ▁of ▁the ▁a rom atic ▁ben z ene ▁and ▁the ▁bridge ▁nit ro gen ▁of ▁the ▁trop ane ▁in ▁the ▁latter ▁P T s . ▁This ▁distance ▁being ▁on ▁a ▁scale ▁of ▁ 5 . 6 ▁Å ▁for ▁ph eny lt rop anes ▁and ▁ 7 . 7 ▁Å ▁for ▁c oca ine ▁or ▁anal ogs ▁with ▁the ▁ben zo y lo xy ▁int act . ▁This ▁may ▁account ▁for ▁P T s ▁increased ▁behavior al ▁stim ulation ▁profile ▁over ▁c oca ine . ▁D iffer ences ▁in ▁binding ▁pot ency ▁have ▁also ▁been ▁explained ▁considering ▁sol v ation ▁effects ; ▁c oca ine ▁containing ▁ 2 β , 3 β - ester ▁groups ▁being ▁calculated ▁as ▁more ▁sol v ated ▁than ▁the ▁W IN - type ▁comp ounds ▁( i . e . ▁tro par il ). ▁High er ▁p K ɑ s ▁of ▁the ▁trop ane ▁nit ro gen ▁( 8 . 6 5 ▁for ▁c oca ine , ▁ 9 . 5 5 ▁for ▁tro par il ▁& ▁ 1 1 . 9 5 ▁for ▁vin yl ▁analog ue ▁ 4 3 a ), ▁decre ased ▁a que ous ▁sol v ation ▁& ▁decre ased ▁conform ational ▁flex ibility ▁added ▁to ▁increased ▁binding ▁aff inity . ▁