Parameters Influencing the Release of Tertiary Alcohols from the Surface of “Spherical” Dendrimers and “Linear” Stylomers by Neighbouring‐Group‐Assisted Hydrolysis of 2‐Carbamoylbenzoates

Size is not all! Investigation of the controlled release of tertiary alcohols from the surface of dendrimers and “stylomers” as polymer model systems (see scheme) showed that the polarity of the conjugates and structural modifications in close proximity to the release unit have a stronger influence on the rates of hydrolysis than the size (generation) or shape (linear or spherical) of the macromolecules. The influence of structural and physico‐chemical parameters on the release of a volatile tertiary alcohol (2‐methyl‐1‐phenyl‐2‐propanol) by neighbouring‐group‐assisted cyclisation of 2‐carbamoylbenzoates at neutral pH was investigated by comparing the covalent‐bond cleavage from the surface of linear, comblike poly(propylene imine) “stylomers” and their corresponding spherical, globular dendrimers. Determination of the kinetic rate constants for the stepwise intramolecular cyclisation of the 2‐carbamoylbenzoate moiety by using HPLC showed that the polarity of the conjugates, and thus their solubility in the aqueous reaction medium, has a stronger influence on the rates of hydrolysis than the size (generation) or shape (linear or spherical) of the macromolecules. Furthermore, structural modifications in close proximity to the release unit, such as the presence of functionalities with catalytic activity, have a strong impact on the release efficiency of the active molecules. An understanding of the physico‐chemical parameters determining the local environment of the covalent‐bond cleavage site is therefore an important prerequisite to transfer the characteristics of small molecules to larger structures such as oligomers and polymers and thus to design efficient macromolecular conjugates for the controlled delivery of bioactive compounds. L'influence des paramètres structurels et physico‐chimiques sur le relargage à pH neutre d'un alcool tertiaire volatil (2‐méthyl‐1‐phényl‐2‐propanol) par cyclisation de 2‐carbamoylbenzoates assistée par un groupe voisin a été étudiée. Les ruptures de liaisons covalentes depuis la surface de poly(propylene imines) en forme de peigne (“stylomères”) d'une part et de leurs analogues sphériques et globulaires (dendrimères) correspondants d'autre part ont été comparées. La détermination par CLHP des constantes cinétiques pour la cyclisation intramoléculaire des unités 2‐carbamoylbenzoate par étapes a montré que la polarité des conjugués, et par conséquent leur solubilité dans le milieu de réaction aqueux, a une influence plus fort