Conformational and static properties of tagged chains in solvents: effect of chain connectivity in solvent molecules.

Polymer chains immersed in different solvent molecules exhibit diverse properties due to multiple spatiotemporal scales and complex interactions. Using molecular dynamics simulations, we study the conformational and static properties of tagged chains in different solvent molecules. Two types of solvent molecules were examined: one type consisted of chain molecules connected by bonds, while the other type consisted of individual bead molecules without any bonds. The only difference between the two solvent molecules lies in the chain connectivity. Our results show a compression of the tagged chains with the addition of bead or chain molecules. Chain molecule confinement induces a stronger compression compared to bead molecule confinement. In chain solvent molecules, the tagged chain's radius of gyration reached a minimum at a monomer volume fraction of ∼0.3. Notably, the probability distributions of chain size remain unchanged at different solvent densities, irrespective of whether the solvent consists of beads or polymers. Furthermore, as solvent density increases, a crossover from a unimodal to a bimodal distribution of bond angles is observed, indicating the presence of both compressed and expanded regions within the chain. The effective monomer-solvent interaction is obtained by calculating the partial radial distribution function and the potential of the mean force. In chain solvents, the correlation hole effect results in a reduced number of nearest neighbors around tagged monomers compared to bead solvents. The calculation of pore size distribution reveals that the solvent nonhomogeneity induced by chain connectivity leads to a broader distribution of pore sizes and larger pore dimensions at low volume fractions. These findings provide a deeper understanding of the conformational behavior of polymer chains in different solvent environments.

Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission.

The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1, a molecular scaffold with a carbazole-pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant Ka =6.04×105  M-1 . Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π-π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure.

Design, synthesis and mechanistic studies of a TICT based fluorogenic probe for lighting up protein HSA.

Human serum albumin (HSA) in blood serves as an important biomarker for clinical diagnosis, and fluorescence sensing method has attracted extensive attention. In this work, a small organic molecule probe, YS8, involving twisted intramolecular charge transfer (TICT) characteristic, was designed and investigated to detect HSA. YS8 kept silent state in fluorescence under physiological conditions, but the encapsulation of YS8 in the hydrophobic subdomain IB region of HSA inhibited the TICT state and produced a clear light-up fluorescent signal. Especially, YS8 was demonstrated to be an efficient fluorogenic probe to discriminate HSA from other proteins including the bovine serum albumin (BSA). Moreover, YS8/HSA complex could be applied in fluorescence imaging in living cells and is also useful in the study of artificial fluorescent protein (AFP).

An environmentally insensitive fluorescent probe for G4 DNA detection: Design, synthesis, and mechanism studies.

G4 DNA structure highly localized to functionally important sites within the human genome, has been identified as a biomarker for regulation of multiple biological processes. Identification G4-responsive fluorescence probes has broad application prospects for addressing G4 biological functions, as well as developing of new families of anticancer drugs. However, some currently designed G4 DNA probes may suffer from serious solvent-dependent effect, and cause unspecific fluorescence that masks the specific signal from G4 DNA. Herein, with a bulky imidazole-cored molecular rotor fusing in D-A building block of carbazole-pyridinium, we constructed a new probe ACPS. This new probe with desirable environmentally insensitive property exhibited a "fluorescence-off" state in various polarity solvents. In the presence of G4 DNA, the intra-molecular rotations would be restricted, triggering intense fluorescence enhancement. Especially, probe ACPS bound to G4 DNA structures with superior selectivity, exhibiting much weaker fluorescence response in the presence of non-G4 DNA structures. This probe was also able to realize fluorescence visualization in cell imaging. Collectively, the probe design strategy eliminates the background fluorescence caused by uncontrollable environmental polarity change, thereby achieving high-fidelity sensing G4 DNA structures in complicated systems.

Selective c-MYC G4 DNA recognition based on a fluorescent light-up probe with disaggregation-induced emission characteristics.

The c-MYC promoter is well-known as an important oncogene, the overexpression of which leads to ∼80% of all solid tumors. The four-stranded G4 present in the c-MYC promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Accordingly, strategies employed for c-MYC G4 DNA sensing have implications for the detection of many human pathologies. However, achieving specificity toward c-MYC G4 over other structurally similar G4s is a challenging task. Here, a supramolecular strategy that relies on the recognition-driven disaggregation of a novel BODIPY probe is outlined. The synthesized probe remained almost non-fluorescent in aqueous media in the aggregation state. Of all the tested G4 and non-G4 DNAs, only c-MYC triggered probe disaggregation and induced a significant increase in fluorescence intensity. The binding details discussed here suggest the basis for the recognition of a particular G4 structure, thus opening up a new way for the design and development of sequence-selective supramolecular G4 probes with desired properties.

Amphiphilic BODIPY-based nanoparticles as "light-up" fluorescent probe for PAEs detection by an aggregation/disaggregation approach.

Phthalic acid eaters (PAEs) play the role of plasticizer and have been widely used in the industrial and plastic production process. But due to not chemically bound in the polymeric matrix, PAEs can be easily released directly and/or indirectly into the environment, and pose a threat the ecosystem and human health. Small-molecule self-assembled nanoparticles have drawn more and more attention due to advantages of precise molecular structure, biocompatibility, great diversity, and tunability in optical properties and functionalities. Here we report the use of disaggregation-induced emission (DIE) based supramolecular assembly to design organic nanoprobe for detection PAEs. In the water solution, the designed small organic fluorophore AJ-1 was aggregated via noncovalent forces to form fluorescence off nanoparticles, but in the presence of PAEs, they disaggregated and produced a clear light-up fluorescent signal. The detection of PAEs with selectivity, sensitivity and rapid response were further achieved. The experiment of recovery of PAEs in real-water sample illustrated the practicability of probe AJ-1 in real-world applications. Besides, cellular uptake assay suggested that AJ-1 could pass through membrane and gather in the cytoplasm.

Development of a carbazole-based fluorescence probe for G-quadruplex DNA: The importance of side-group effect on binding specificity.

G-quadruplex DNAs are highly prevalent in the human genome and involved in many important biological processes. However, many aspects of their biological mechanism and significance still need to be elucidated. Therefore, the development of fluorescent probes for G-quadruplex detection is important for the basic research. We report here on the development of small molecular dyes designed on the basis of carbazole scaffold by introducing styrene-like substituents at its 9-position, for the purpose of G-quadruplex recognition. Results revealed that the side group on the carbazole scaffold was very important for their ability to selectively recognize G-quadruplex DNA structures. 1a with the pyridine side group displayed excellent fluorescence signal turn-on property for the specific discrimination of G-quadruplex DNAs against other nucleic acids. The characteristics of 1a were further investigated with UV-vis spectrophotometry, fluorescence, circular dichroism, FID assay and molecular docking to validate the selectivity, sensitivity and detailed binding mode toward G-quadruplex DNAs.