Impact of Local Stiffness on Entropy Driven Microscopic Dynamics of Polythiophene

© 2020, The Author(s). We exploited the high temporal and spatial resolution of neutron spin echo spectroscopy to investigate the large-scale dynamics of semiflexible conjugated polymer chains in solutions. We used a generalized approach of the well-established Zimm model of flexible polymers to describe the relaxation mode spectra of locally stiff polythiophene chains. The Zimm mode analysis confirms the existence of beads with a finite length that corresponds to a reduced number of segmental modes in semiflexible chains. Irrespective of the temperature and the molecular weight of the conjugated polymer, we witness a universal behavior of the local chain stiffness and invariability of the bead length. Our experimental findings indicate possibly minor role of the change in π-electron conjugation length (and therefore conjugated backbone planar to non-planar conformational transition) in the observed thermochromic behavior of polythiophene but instead point on the major role of chain dynamics in this phenomenon. We also obtained the first experimental evidence of an existence of a single-chain glass state in conjugated polymers

Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease

Purpose: The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson’s disease (PD) pathology, and be detectable with one or more imaging modalities. Procedure: A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson’s and Alzheimer’s disease tissue, alpha-synuclein oligomers and inclusions in two cell culture models, and alpha-synuclein aggregates in cortical neurons of a transgenic mouse model. Finally, compounds were tested for blood–brain barrier permeability using intravital microscopy. Results: Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer’s pathology. The cell culture models and transgenic mouse models that exhibit alpha-synuclein aggregation did not prove predictive for ligand binding. The compounds had favorable physicochemical properties, and several were brain permeable. Conclusions: Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology

Amplifying fluorescent conjugated polymer sensor for singlet oxygen detection

A higher energy gap concept was applied towards designing an efficient turn-on amplifying sensor for singlet oxygen - an important biomedical and environmental monitoring analytical target. The concept is based on modulation of intramolecular energy transfer in fluorescent conjugated polymers through the formation of a higher energy gap roadblock upon reaction with a target analyte. The polymer sensor incorporates 1,4-disubstituted tetracene units which act as reactive sites for singlet oxygen. The resulting polymer sensor demonstrates significant fluorescent signal amplification and a broader analyte detection range relative to a corresponding small-molecule sensor

Rational design of highly responsive pH sensors based on DNA i-motif

Availability of strategies for molecular biosensing over a finely adjustable dynamic range is essential for understanding and controlling vital biological processes. Herein we report design principles of highly responsive pH sensors based on a DNA i-motif where both response sensitivity and transition midpoint can be tuned with high precision over the physiologically relevant pH interval. The tuning is accomplished via rational manipulations of an i-motif structure as well as incorporation of allosteric control elements. This strategy delivers molecular sensing systems with a transition midpoint tunable with 0.1 pH units precision and with a total response range as narrow as 0.2 pH units which can be adjusted to a variety of outputs (e.g., fluorescent readout). The potential of the presented approach is not limited by pH sensing but may extend toward manipulation of other quadruplex based structures or the development of ultraresponsive elements for artificial molecular machines and signaling systems

Chemosensory performance of molecularly imprinted fluorescent conjugated polymer materials

Fluorescent conjugated polymers are an attractive basis for the design of low detection limit sensing devices owing to their intrinsic signal amplification capability. A simple and universal method to rationally control or fine-tune the chemodetection selectivity of conjugated polymer materials toward a desired analytical target would further benefit their applications. In a quest of such a method we investigated a general approach to cross-linked molecularly imprinted fluorescent conjugated polymer (MICP) materials that possess an intrinsic capability for signal transduction and have potential to enhance selectivity and sensitivity of sensor devices based on conjugated polymers. To study these capabilities, we prepared an MICP material for the detection of 2,4,6-trinitrotoluene and related nitroaromatic compounds. We found the imprinting effect in this material to be based on analyte shape/size recognition being substantial and generally overcoming other competing thermodynamically determined trends. The described molecularly imprinted fluorescent conjugated polymers show remarkable air stability and photostability, high fluorescence quantum yield, and reversible analyte binding and therefore are advantageous for sensing applications due to the ability to preprogram their detection selectivity through a choice of an imprinted template

“Higher Energy Gap” Control in Fluorescent Conjugated Polymers: Turn-On Amplified Detection of Organophosphorous Agents

Chemo- and biosensors based on fluorescent conjugated polymers benefit from greater detection sensitivity due to amplification of the electronic perturbations produced by analyte binding. This amplification stems from the exciton-transporting properties of conjugated polymers. In a conventional sensor design paradigm, excitons migrate from the bulk of the polymer to the analyte binding sites which can be either fluorescence quenching sites (turn-off sensors) or lower energy fluorophores (turn-on sensors). Herein, we proposed an alternative design paradigm when analyte binding creates a higher energy gap site in the polymer backbone. In the case of isolated polymer chains in dilute solution, these higher energy gap sites act as “roadblocks” for migrating excitons, effectively limiting the exciton migration length. This is responsible for an amplified enhancement of fluorescence of the conjugated polymer sensor. As a proof of concept, we utilized this design principle to develop an amplifying turn-on sensor for organophosphorous warfare agents mimics and demonstrated substantial signal gain and much broader analyte detection range relative to the corresponding small-molecule analogue. This new paradigm expands the generality and universality of the signal amplification concept in conjugated polymers and can be used to design amplifying turn-on fluorescent sensors for various practically useful analytes

Thin-film ratiometric fluorescent chemosensors with tunable performance characteristics

A simple method for tuning the performance characteristics of fluorescent ratiometric sensors based on surface-immobilized monolayers of π-conjugated molecules enabled gradual adjustment of the sensitivity and the analyte detection range of the sensor. This approach has been applied to fine-tune the sensing performance of a prototype ratiometric chemosensor for fluoride ions