Hydrogen-bonding molecules in medicinal chemistry and material science

The bis-urea compound, 2-(3-4-[3-S -(1-tert-butoxycarbonyl-2-methyl-propyl)-ureidomethyl]-benzyl- S-ureido-3-methyl-butyric acid tert-butyl ester (8), displays enantioselective complexation of N-CBZ-glutamate in chloroform (Ka 3400 M-1 and 4800 M-1 for L and D enantiomers, respectively). The single-crystal X-ray structure of 8 indicates that the chiral appendages responsible for enantioselective recognition are positioned away from the chiral center of the glutamate, thus reducing the effectiveness of 8 to induce an enantioselective environment.; The simple bisguanidinium molecules possessing a common 1,3-xylylene spacer (1,3-bis(guanidinomethyl)benzene 43 and 1,3-bis(guanidinocarbonyl)benzene 56) inhibit the protein-protein interaction of the Ras/Raf association, which is involved in the signal transduction pathway responsible for cell growth and differentiation. These molecules display an IC₅₀ of 100 $m$M. Substitution on the N1 and N3 nitrogens of the guanidiniums retards inhibitory activity while alkylation on the N 1 nitrogen stabilizes the Ras/Raf complex at 1000 $m$M.; Carbamoyl isothiocyanates have been used in the generation of protected thioureas. In the presence of an amine the protected thioureas were cleanly converted to the protected guanidine with EDCI in dichloromethane. This procedure was amenable to the formation of bisguanidine compounds in high yield.; Highly-fluorinated bis-urea compounds have been developed for the gelation of fluorinated solvents and supercritical CO₂. Based on the X-ray crystal structure of 8, these bis-urea molecules self-associate to form fibrous aggregates which create a three-dimensional network which immobilizes the solvent. Evidence of this association is given by the scanning electron micrographs (SEM) of the dry gels of 1,6-bis[(di-1H,1H,2H,2H-perfluorodecyl- L-aspartyl)carbonylamino) hexane (51) and 1,12-bis[(di-1H,1H,2H,2H-perfluorodecyl- L-aspartyl)carbonylamino) dodecane (53). In supercritical CO₂, compound 51 formed an aerogel while compound 52 formed an xerogel. Thermodynamic analysis of gels formed in perfluoromethylcyclohexane indicated that longer flexible spacers increased the enthalpy of melting of the gel ($D$H_m = 46 kJ$\dot{}$mol-1, 249 kJ$\dot{}$mol-1 for 51 and 53, respectively).