Development of Colorimetric and Fluorescent Antibiotic Biosensors and Synthesis of Drug-Related Biomimetic Molecules for Calcium Carbonate Polymorph Control and Stabilization
Abstract
Polydiacetylene (PDA) polymers are conjugated macromolecules with desirable sensing
properties. The presence of alternate double and triple bonds (en-yne subunits)
generates electron delocalization in the PDA backbone, yielding a characteristic blue
color, which changes to red upon environmental perturbations to the conjugated
backbone structure. In chapter 1 PDA polymers containing a functional monomer 10,12-
pentacosadiynoic acid-vancomycin conjugate (PCDA-Van) were prepared. Syntheses of
different monomers containing different polar head groups were carried out to investigate
a compatible monomer with PCDA-van stability. Gram-positive bacterial cell wall
sequencing oligopeptides (OP) D-Ala-D-Ala and L-Lys-D-Ala-D-Ala were synthesized as
a model for bacterial sensing. The PCDA-Van provided rapid and direct detection of OP
visibly through a blue to purple color transition upon the addition of OP. PCDA-Van
containing liposomes became fluorescent in the presence of S. aureus.
In chapter 2, PCDA-peptide was synthesized for the detection of gram-positive bacteria
Methicillin-resistant Staphylococcus aureus (MRSA). PDA-peptide stability was optimized
by using three monomer system to prepare liposomal polymer. PDA-peptides were
labelled with a dabsyl-labeled lipid to obtain fluorescent images to analyze the bacterial
interaction with liposomes. Next, a diphenyl diacetylene (DA) linker was synthesized,
coupled with peptides (Pep-DA-Pep), to prepare a PDA containing hydrogel with pH
sensing applications. At acidic pH, antimicrobial agents were incorporated into the PDA
hydrogel and upon elevated pH gel-to-sol transition delivered the drug to the target
alkaline infection site.
In chapter 3, the ability of biomimetic molecules to control the carbonation and
precipitation process of CaCO3 in cementitious materials was investigated. The purpose
of the study was to enhance the stability and function of cementitious material. A series
of different bisphosphonate (BPs) molecules were synthesized, containing different alkyl
chains and a distal functional group. Experiments were performed with CaCl2 solution in
the presence of different BPs moieties for CaCO3 precipitations. BPs with longer alkyl
chain molecules showed the enhanced formation of vaterite and amorphous calcium
carbonate (ACC). Characterization of the precipitation was done with atomic force
microscopy (AFM), thermogravimetric analysis (TGA), conductivity experiments, Fourier transform infrared spectroscopy (FTIR) and was supported with computational studies.
In chapter 4, future work is described to further our study on the biosensing of infective
species and the preparation of metal carbonate binding molecules to target bacterial
species and effect on CaCO3 precipitation respectively.