A general approach to differential sensing using synthetic molecular receptors.

Differential sensing is continuing to develop as an alternative to traditional, selective chemosensing techniques. This technique takes a cue from how the human senses of taste and smell operate in order to obtain qualitative and even quantitative data on single analytes and mixtures. Whereas classical chemosensing techniques inspired by the 'lock-and-key' approach depend on the development of a selective receptor for a target analyte, pattern-based sensing depends on the development of an array of cross-reactive receptors, which produce a collection of responses upon the array's interaction with a target analyte.

Triazine dendrimers with orthogonally protected amines on the periphery. Masking amines with Dde and BOC groups provides an alternative to carrying protected alcohols and disulfides through an iterative synthesis.

An orthogonally protected dendrimer based on melamine displaying 24 Boc-protected amines (Boc is t-butoxycarbonyl) and 12 Dde-protected (Dde is N-2-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) amines was synthesized using a convergent route in four linear steps in 43% overall yield to provide 5 g of product. Postsynthetic manipulation of this dendrimer produced a 57 kDa macromolecule bearing poly(ethylene glycol) groups and pyridyldisulfide groups linked via carbamate and amide bonds, respectively. These orthogonally protected amines provide more reactive handles for chemical modification when compared to other groups, notably hydroxyls, that have been explored.

Thiol-disulfide exchange yields multivalent dendrimers of melamine.

[reaction: see text] Thiol-disulfide exchange can be used to prepare multivalent conjugates of a small molecule or octapeptide displayed on dendrimers based on melamine. Exchange of four or eight thiopyridyl groups by captopril occurs at room temperature in methanol almost quantitatively. Exchange using the peptide requires higher temperatures and guanidinium chloride in DMF.