ABSTRACT
The barcoded resins (BCRs) were introduced recently as a platform for encoded combinatorial chemistry. One of the main challenges yet to be overcome is the demonstration that a large number of BCRs could be generated and classified with high confidence. Here, we describe the synthesis and classification of 630 polystyrene-based copolymers prepared from the combinatorial association of 15 spectroscopically active styrene monomers. Each of the 630 copolymers displayed a unique vibrational fingerprint (infrared and Raman), which was converted into a spectral vector. To each of the 630 copolymers, a vector of the known (reference) composition was assigned. Unknown (prediction) vectors were decoded using multivariate data analysis. From the inner product of the reference and prediction vectors, a correlation map comparing 396 900 copolymer pairs (630 x 630) was generated. In 100% of the cases, the highest correlation was obtained for polymer pairs in which the reference and prediction vectors correspond to copolymers prepared from identical styrene monomers, thus demonstrating the high reliability of this encoding strategy. We have also established that the spectroscopic barcodes generated from the Raman and infrared spectra are independent of the copolymers' morphology (beaded versus bulk polymers). Besides the demonstration of the generality of the polymer barcoding strategy, the analytical methods developed here could in principle be extended to the investigation of the composition and purity of any other synthetic polymer and biopolymer library, or even scaffold-based combinatorial libraries.
Subject(s)
Combinatorial Chemistry Techniques , Polystyrenes , Resins, Synthetic , Small Molecule Libraries , Magnetic Resonance Spectroscopy , Molecular Structure , Polystyrenes/chemical synthesis , Polystyrenes/chemistry , Polystyrenes/classification , Resins, Synthetic/chemical synthesis , Resins, Synthetic/chemistry , Resins, Synthetic/classification , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Small Molecule Libraries/classification , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, RamanABSTRACT
Barcoded resins (BCRs) were recently introduced as a potential platform for pre-encoded multiplexed synthesis, screening, and biomedical diagnostics. A key step toward the development of this strategy is the ability to rapidly interrogate and classify the BCRs in a high-throughput, noninvasive manner. Here, we describe a one-step strategy based on Raman mapping and Fourier transform infrared imaging to classify and spatially resolve randomly distributed BCRs. To illustrate this methodology, mixtures of up to 25 different BCRs were imaged and classified with 100% confidence. This strategy can be readily extended to a larger pool of resins, provided each BCR features a unique vibrational fingerprint (spectroscopic barcode). We have also established that reliable single-bead Raman spectra can be recorded in 10 ms, thus confirming that Raman mapping, in particular, could be a very fast method to classify the BCRs.
Subject(s)
Resins, Synthetic/chemistry , Models, Molecular , Resins, Synthetic/chemical synthesis , Spectroscopy, Fourier Transform Infrared/methods , Spectrum Analysis, Raman/methods , StyreneABSTRACT
The first paper of the series, which focused on the effect of polydispersity on the self-assembly of block copolymer vesicles, showed that an increase in the width of the poly(acrylic acid) (PAA) block length distribution resulted in a decrease in the size of the vesicles formed. In this paper, the rest of the phase diagram is explored. For the present study, a series of polystyrene-b-poly(acrylic acid) copolymers of an identical polystyrene length of 325 units but of varying degrees of polymerization of PAA was synthesized. Mixtures of the copolymers were made to artificially broaden the molecular weight distribution of PAA at a constant number average of 48 in the polydispersity index (PDI) range of 1.1-3.3. The mixtures were dissolved in dioxane, and water was added slowly to predetermined amounts. Transmission electron microscopy was used to observe aggregate morphologies at different water contents and PAA PDIs. At low water contents, dynamic light scattering was also used to measure the sizes of the aggregates. A partial phase diagram as a function of the water content and PAA PDI was obtained. Large compound micelles and spherical micelles (average diameter of 40 nm) were found at low water contents; however, at a water content of 12% (w/w), a continuum of morphologies from spheres to rods to vesicles was found with increasing PAA PDI. In addition, each copolymer was investigated by itself under identical conditions to those used for the mixtures to determine if there was any segregation of the individual polymers into separate aggregates. No evidence for such segregation was found.
