An ammonium picket porphyrin that targets bacterial membranes has been prepared and shown to bind to phosphatidylglycerol (PG), a bacterial lipid, when the lipid was in solution, contained within synthetic membrane vesicles, or when in Gram-negative and Gram-positive bacterial membranes. The multifunctional receptor was designed to interact with both the phosphate anion portion and neutral glycerol portion of the lipid headgroup. The receptor's affinity and selectivity for binding to surfactant vesicles or lipid vesicles that contain PG within their membranes was directly measured using fluorescence correlation spectroscopy (FCS). FCS demonstrated that the picket porphyrin's binding pocket was complementary for the lipid headgroup, since simple Coulombic interactions alone did not induce binding. 1H NMR and isothermal titration calorimetry (ITC) were used to determine the receptor's binding stoichiometry, receptor–lipid complex structure, binding constant, and associated thermodynamic properties of complexation in solution. The lipid–receptor binding motif in solution was shown to mirror the binding motif of membrane-bound PG and receptor. Cell lysis assays with E. coli (Gram-negative) and Bacillus thuringiensis (Gram-positive) probed with UV/Visible spectrophotometry indicated that the receptor was able to penetrate either bacterial cell wall and to bind to the bacterial inner membrane.

The lipid binding ability of four urea-picket porphyrins designed to bind to both the phosphate anion portion as well as the glycerol hydroxyl groups of phosphatidylglycerol (PG) has been investigated. Isothermal titration calorimetry (ITC) and 1H NMR were used to determine the receptor’s stoichiometry of binding, association constants, and both the enthalpy and entropy of binding with the PG anion. Spectral evidence shows that the phosphate anion portion of PG is hydrogen bonded to the urea groups of the receptors. This binding interaction orients the PG anion in the receptor pocket such that its glycerol hydroxyl groups can align with a third urea picket, and results are furnished that suggest this multifunctional interaction does occur. The structure of the entire picket was found to influence the enthalpy and entropy of lipid binding. The synthesis of tetrabutlyammonium phosphatidylglycerol (TBAPG), and a detailed spectral characterization of its headgroup, is also presented.

ITC titration studies of a family of bis-ammonium receptors based upon a scaffold of two bis-linked phenol rings show that several of the receptors bind to both dihydrogenphosphate and phosphatidylglycerol anions in a similar binding motif. Thermodynamic properties determined from ITC show that anion binding is entropy driven. Job plots determined from 1H NMR clearly demonstrate that anion−receptor binding stoichiometry is dependent on the receptor’s length of its bis-amine linkage.

A method for the one-step C-ureidoalkylation of phenol, anisole, or aniline rings furnishing ArCH2NHCONHR (Ar = benzyl) products in moderate to good yields is described. With phenol ring systems, higher yields were attained when the reaction was worked up with an acidic ethanethiol addition to cleave any O-ureidoalkylation products that formed during the reaction.

An ammonium picket porphyrin that targets bacterial membranes has been prepared and shown to bind to phosphatidylglycerol (PG), a bacterial lipid, when the lipid was in solution, contained within synthetic membrane vesicles, or when in Gram-negative and Gram-positive bacterial membranes. The multifunctional receptor was designed to interact with both the phosphate anion portion and neutral glycerol portion of the lipid headgroup. The receptor's affinity and selectivity for binding to surfactant vesicles or lipid vesicles that contain PG within their membranes was directly measured using fluorescence correlation spectroscopy (FCS). FCS demonstrated that the picket porphyrin's binding pocket was complementary for the lipid headgroup, since simple Coulombic interactions alone did not induce binding. 1H NMR and isothermal titration calorimetry (ITC) were used to determine the receptor's binding stoichiometry, receptor–lipid complex structure, binding constant, and associated thermodynamic properties of complexation in solution. The lipid–receptor binding motif in solution was shown to mirror the binding motif of membrane-bound PG and receptor. Cell lysis assays with E. coli (Gram-negative) and Bacillus thuringiensis (Gram-positive) probed with UV/Visible spectrophotometry indicated that the receptor was able to penetrate either bacterial cell wall and to bind to the bacterial inner membrane.