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

Abstract

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.

Profragrances and Properfumes

“…Baseline separation of quite large linear or spherical (Figure 13.6) from their corresponding mono-phthalimide derivatives by analytical HPLC allowed the comparison of the rate constants for a series of compounds with different shape, size and number of 2-carbamoylbenzoate units per molecule. 32,33 Due to the limited solubility of the larger structures in the reaction medium (and to take into account the presence of surfactants in many practical applications) the rate constants for the neighbouring-group-assisted cyclizations were measured in the presence of a non-ionic surfactant.…”

“…33 The kinetic data show that the polarity of the precursors, which is related to their solubility in the aqueous solution, has a stronger influence on the rates of alcohol release than the shape (linear or spherical) or the size (number of release units) of the conjugates.…”

“…Comparison with precursor 31, which is lacking the tertiary amino function, shows that the release of the tertiary alcohol is slowed down by several orders of magnitude. 33 The understanding of the physicochemical parameters which have an impact on the environment close to the covalent bond cleavage site plays an important role in the conception of polymeric delivery systems.…”

Functionalized cellulose nanocrystals as nanocarriers for sustained fragrance release

“…4,5 The chemical and physical conditions of formulations used in various consumer applications as well as the conditions and rates under which fragrance release should occur can vary over wide ranges, and therefore many different substrates and labile bonds have been explored in the context of polymer-based pro-fragrance design. [15][16][17][18][19][20][21][22] Based on the hypothesis that monosaccharide-based pro-fragrances adsorb well on cotton textiles, which is an important requirement for their use in laundry products, 20 we recently reported the investigation of new galactose-based pro-fragrances that were prepared by reacting δ-damascone in a 1,4-addition with mercaptoacetic acid and coupling this product with 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose, which was optionally deprotected to a more hydrophilic variant. 23 Fragrance release occurred via a retro 1,4-Michael-type reaction over the course of days, at rates that were pH dependent, and at a level that represents an increase by over two orders of magnitude in comparison to the neat fragrance.…”

Controlled Release of Damascone from Poly(styrene-co-maleic anhydride)-based Bioconjugates in Functional Perfumery

“…Reaction conditions allowing covalent bond cleavage and the release of the volatile biomolecule from its precursor comprise changes in temperature or pH, hydrolysis, oxidation and exposure to daylight or enzymes [9][10][11][12][13][14][15]. In addition to small molecular precursors, polymer bioconjugates have been investigated for the slow release of volatile compounds [9][10][11][16][17][18][19][20][21][22][23][24][25][26][27][28]. The ease of structural modulation of polymeric materials was expected to allow the selective influence of the properties of the delivery systems and their adaptation to the particular requirements of the formulations into which they were incorporated.…”