Understanding the unfolding mechanism of human telomeric G-quadruplex using steered molecular dynamics simulation

The unfolding pathway of human telomeric G-quadruplex with three G-tetrads in presence of K+ and Na+ ions, separately using steered molecular dynamics (SMD) simulation is reported. The isothermal-isobaric all-atoms classical molecular dynamics simulation results show that three K+ and three Na+ ions are required within the central channel of the G-quadruplex (PDB ID: 143D and 2HY9, respectively) to stabilize the respective overall structure. To obtain the unfolded G-quadruplex which is ~5-6 times of its initial contour length, SMD simulation has been carried out by fixing one end of the G-quadruplex and constraining the other end to move only along the long axis (z-axis). The SMD results suggest that the unfolding of G-quadruplex occurs via G-triplex intermediates independent of the presence of cations (K+, Na+).

A Thiazole Coumarin (TC) turn-on fluorescence probe for AT-base pair detection and multipurpose applications in different biological systems

Sequence-specific recognition of DNA by small turn-on fluorescence probes is a promising tool for bioimaging, bioanalytical and biomedical applications. Here, the authors report a novel cell-permeable and red fluorescent hemicyanine-based Thiazole Coumarin (TC) probe for DNA recognition, nuclear staining and cell cycle analysis. TC exhibited strong fluorescence enhancement in the presence of DNA containing AT-base pairs, but did not fluoresce with GC sequences, single-stranded DNA, RNA and proteins. The fluorescence staining of HeLa S3 and HEK 293 cells by TC followed by DNase and RNase digestion studies depicted the selective staining of DNA in the nucleus over the cytoplasmic region. Fluorescence-Activated Cell Sorting (FACS) analysis by flow cytometry demonstrated the potential application of TC in cell cycle analysis in HEK 293 cells. Metaphase chromosome and malaria parasite DNA imaging studies further confirmed the in vivo diagnostic and therapeutic applications of probe TC. Probe TC may find multiple applications in fluorescence spectroscopy, diagnostics, bioimaging and molecular and cell biology

Understanding the unfolding mechanism of human telomeric G-quadruplex using steered molecular dynamics simulation

907-912The unfolding pathway of human telomeric G-quadruplex with three G-tetrads in presence of K+ and Na+ ions, separately using steered molecular dynamics (SMD) simulation is reported. The isothermal-isobaric all-atoms classical molecular dynamics simulation results show that three K+ and three Na+ ions are required within the central channel of the G-quadruplex (PDB ID: 143D and 2HY9, respectively) to stabilize the respective overall structure. To obtain the unfolded G-quadruplex which is ~5-6 times of its initial contour length, SMD simulation has been carried out by fixing one end of the G-quadruplex and constraining the other end to move only along the long axis (z-axis). The SMD results suggest that the unfolding of G-quadruplex occurs via G-triplex intermediates independent of the presence of cations (K+, Na+)

Exploring Thioxanthone Derivatives as Singlet Oxygen Photosensitizers for Photodynamic Therapy at the Near-IR Region

In the lowest excited triplet state, the excited photosensitizer reacts with tissue oxygen and forms reactive oxygen species (ROS), which kills tissue cells in photodynamic therapy (PDT). Metal-free thio-based pure organic molecules and analogous nucleobases can be used as photosensitizers for PDT applications. Using quantum chemical methods, we studied one- and two-photon optical absorptions, fluorescence, and other excited-state properties of substituted thioxanthone derivatives for their potential as photosensitizers for PDT. Our calculated values were compared with the available experimental data. The calculation of the intersystem crossing rate constant for these photosensitizers explains the high quantum yield of the formation of ROS, as reported experimentally. The excited triplet-state population of the photosensitizer occurs through the 1π–π* → 3n−π* channel of intersystem crossing and increases in the presence of halogen substitution

Tuning of Hyperpolarizability, One- and Two-Photon Absorption of D-A and D-A-A Type Intramolecular Charge Transfer Based Sensors

Solvents play an important role in shaping the intramolecular charge transfer (ICT) properties of π-conjugated molecules, which in turn can affect their one-photon absorption (OPA) and two-photon absorption (TPA) as well as the static (hyper)polarizabilities. Here, we study the effect of solvent and donor-acceptor arrangement on linear and nonlinear optical (NLO) response properties of two novel ICT-based fluorescent sensors, one consisting of hemicyanine and dimethylaniline as electron withdrawing and donating groups (molecule 1), respectively and its boron-dipyrromethene (BODIPY, molecule 2)-fused counterpart (molecule 3). Density functional theoretical (DFT) calculations using long-range corrected CAM-B3LYP and M06-2X functionals, suitable for studying properties of ICT molecules, are employed to calculate the desired properties. The dipole moment (µ) as well as the total first hyperpolarizability (βtotal) of the studied molecules in the gas phase is dominantly dictated by the component in the direction of charge transfer. The ratios of vector component of first hyperpolarizability (βvec) to βtotal also reveal unidirectional charge transfer process. The properties of the medium significantly affect the OPA, hyperpolarizability and TPA properties of the studied molecules. Time dependent DFT (TDDFT) calculations suggest interchanging between two lowest excited states of molecule 3 from the gas phase to salvation. The direction of charge polarization and dominant transitions among molecular orbitals involved in the OPA and TPA processes are studied. The results presented are expected to be useful in tuning the NLO response of many ICT-based chromophores, especially those with BODIPY acceptors.<br /

Computational studies on structural and optical properties of single-stranded DNA encapsulated silver/gold clusters

Using a combined approach of molecular dynamics (MD) and density functional theoretical (DFT) calculations, we perform the investigation of structures, energetics and optical properties of Ag12 and Au12 clusters in the presence of single-stranded DNA (ssDNA) scaffold of various nucleobase sequences (i.e. ssdA12, ssdT12, ssdG12 and ssdC12). The individual ssDNA undergoes various conformational changes in the presence of different metal clusters during the course of 1.5 ns MD simulations in aqueous media. We find that ssdG12 interacts strongly with the Ag12 cluster while ssdA12 shows greater binding affinity towards the Au12 cluster. We also find that the two different kinds of binding modes of a nucleobase play a key role in deciding the overall structure and stability of the complex while interacting with metal clusters. The metal clusters form nanocomposites with ssDNA either via p-stacking and/or by the interaction mediated through specific atoms (nitrogen and/or oxygen) present in the nucleobases. The optical response properties of these Ag12/Au12-ssDNA composites together with the bare metal clusters are calculated with the MD simulated structures alone, which are comparable with experimental results. The optical absorption characteristics of metal clusters are little affected by the presence of ssDNA scaffold due to the frontier orbital localization mainly on the metal clusters or ssDNA

Understanding the Binding Mechanism of Various Chiral SWCNTs and ssDNA: A Computational Study

Molecular dynamics (MD) simulations have been carried out to understand the binding mechanism of various chiral single-walled carbon nanotubes (SWCNTs) and single-stranded DNA (ssDNA) of four different nucleobase sequences (i.e., ssdA₁₄, ssdT₁₄, ssdG₁₄, and ssdC₁₄, where, A, T, G, and C are adenine, thymine, guanine, and cytosine, respectively) in aqueous media at room temperature (300 K) and atmospheric pressure (1 atm). The simulations studies reveal that ssDNA undergoes rapid structural changes and wrap around the SWCNTs via π-stacking interactions between SWCNT’s wall and the nucleobases of ssDNA. Our computations demonstrate that the length of the ssDNA plays an important role during the wrapping process. Moreover, it suggests that the length of the sequence should be proportional to the diameter of the SWCNT, in order to overcome the intralocked π-stacking interactions between the nucleobases of ssDNA sequence. Also, in our classical MD simulation, we do not observe the correlation between the diameter of SWCNTs and the sequences of ssDNA, which indicates the importance of electronic factors of these systems. In order to understand the electronic contributions of these systems, the quantum calculations have been performed at Hartree–Fock level for the 17 ns MD simulated structures. The quantum chemical calculations provide evidence that the highly stable ssDNA@SWCNT hybrid possesses a larger HOMO–LUMO gap

Up-Conversion Intersystem Crossing Rates in Organic Emitters for Thermally Activated Delayed Fluorescence: Impact of the Nature of Singlet vs Triplet Excited States

The rates for up-conversion intersystem crossing (UISC) from the T₁ state to the S₁ state are calculated for a series of organic emitters with an emphasis on thermally activated delayed fluorescence (TADF) materials. Both the spin–orbit coupling and the energy difference between the S₁ and T₁ states (Δ<i>E</i>_ST) are evaluated, at the density functional theory (DFT) and time-dependent DFT levels. The calculated UISC rates and Δ<i>E</i>_ST values are found to be in good agreement with available experimental data. Our results underline that small Δ<i>E</i>_ST values and sizable spin–orbit coupling matrix elements have to be simultaneously realized in order to facilitate UISC and ultimately TADF. Importantly, the spatial separation of the highest occupied and lowest unoccupied molecular orbitals of the emitter, a widely accepted strategy for the design of TADF molecules, does not necessarily lead to a sufficient reduction in Δ<i>E</i>_ST; in fact, either a significant charge-transfer (CT) contribution to the T₁ state or a minimal energy difference between the local-excitation and charge-transfer triplet states is required to achieve a small Δ<i>E</i>_ST. Also, having S₁ and T₁ states of a different nature is found to strongly enhance spin–orbit coupling, which is consistent with the El-Sayed rule for ISC rates. Overall, our results indicate that having either similar energies for the local-excitation and charge-transfer triplet states or the right balance between a substantial CT contribution to T₁ and somewhat different natures of the S₁ and T₁ states, paves the way toward UISC enhancement and thus TADF efficiency improvement

Enhancing Selectivity and Kinetics in Oxidative Photocyclization by Supramolecular Control

International audiencePhotochemical reactions typically proceed via multiple reaction pathways, yielding a variety of isomers and products. Enhancing the selectivity is challenging. Now, the potential of supramolecular control for oxidative photocyclization of a tetraarylethylene, containing a stereogenic -C=C- bond, is demonstrated. In solution, this photochemical reaction produces three constitutional isomers (substituted phenanthrenes), with slow kinetics. When the reactant is assembled into a crystalline framework, only one product forms with accelerated kinetics. Key to this selectivity enhancement is the integration into a surface grown metal-organic framework (SURMOF); the dramatic gain in selectivity is ascribed to the hindrance of the rotational freedom of the -C=C- double bond. The structure of the MOF is key; the corresponding reaction in the solid does not result in such a high increase in selectivity. A striking change of luminescence properties after photocyclization is observed