Conformational Relaxation Research Articles

Alkyl-Doping Enables Significant Suppression of Conformational Relaxation and Intermolecular Nonradiative Decay for Improved Near-Infrared Fluorescence Imaging.

Despite various efforts to optimize the near-infrared (NIR) performance of perylene diimide (PDI) derivatives for bio-imaging, convenient and efficient strategies to amplify the fluorescence of PDI derivatives in biological environment and the intrinsic mechanism studies are still lacking. Herein, we propose an alkyl-doping strategy to amplify the fluorescence of PDI derivative-based nanoparticles for improved NIR fluorescence imaging. The developed PDI derivative, OPE-PDI, shows much brighter in n-Hexane (HE) compared with that in other organic media, and the excited state dynamics investigation experimentally elucidates the solvent effect-induced suppression of intermolecular energy transfer and intramolecular nonradiative decay as the underlying mechanism for the fluorescence improvement. Theoretical calculations reveal the lowest reorganization energies of OPE-PDI in HE among various solvents, indicating the effectively suppressed conformational relaxation to support the strongest radiative decay. Inspired by this, an alkyl atmosphere mimicking HE is constructed by incorporating the octadecane into OPE-PDI-based nanoparticles, permitting up to 3-fold fluorescence improvement compared with the counterpart nanoparticles. Owing to the merits of high brightness, anti-photobleaching, and low biotoxicity for the optimal nanoparticles, they have been employed for probing and long-term monitoring of tumor. This work highlights a facile strategy for the fluorescence enhancement of PDI derivative-based nanoparticles.

Data-Driven Learning of the Generalized Langevin Equation with State-Dependent Memory.

We present a data-driven method to learn stochastic reduced models of complex systems that retain a state-dependent memory beyond the standard generalized Langevin equation with a homogeneous kernel. The constructed model naturally encodes the heterogeneous energy dissipation by jointly learning a set of state features and the non-Markovian coupling among the features. Numerical results demonstrate the limitation of the standard generalized Langevin equation and the essential role of the broadly overlooked state-dependency nature in predicting molecule kinetics related to conformation relaxation and transition.

Alkyl‐Doping Enables Significant Suppression of Conformational Relaxation and Intermolecular Nonradiative Decay for Improved Near‐Infrared Fluorescence Imaging

AbstractDespite various efforts to optimize the near‐infrared (NIR) performance of perylene diimide (PDI) derivatives for bio‐imaging, convenient and efficient strategies to amplify the fluorescence of PDI derivatives in biological environment and the intrinsic mechanism studies are still lacking. Herein, we propose an alkyl‐doping strategy to amplify the fluorescence of PDI derivative‐based nanoparticles for improved NIR fluorescence imaging. The developed PDI derivative, OPE‐PDI, shows much brighter in n‐Hexane (HE) compared with that in other organic media, and the excited state dynamics investigation experimentally elucidates the solvent effect‐induced suppression of intermolecular energy transfer and intramolecular nonradiative decay as the underlying mechanism for the fluorescence improvement. Theoretical calculations reveal the lowest reorganization energies of OPE‐PDI in HE among various solvents, indicating the effectively suppressed conformational relaxation to support the strongest radiative decay. Inspired by this, an alkyl atmosphere mimicking HE is constructed by incorporating the octadecane into OPE‐PDI‐based nanoparticles, permitting up to 3‐fold fluorescence improvement compared with the counterpart nanoparticles. Owing to the merits of high brightness, anti‐photobleaching, and low biotoxicity for the optimal nanoparticles, they have been employed for probing and long‐term monitoring of tumor. This work highlights a facile strategy for the fluorescence enhancement of PDI derivative‐based nanoparticles.

Rotational Spectroscopy as a Tool to Characterize Sweet Taste: The Study of Dulcin.

According to old theories of sweetness, the perception of sweet substances is closely linked to the arrangement of atoms within them. To assess the validity of these theories, we conducted an analysis of the structure of the artificial sweetener dulcin for the first time, utilizing microwave spectroscopy and a laser ablation source. These techniques have enabled the identification of two conformers, which are stabilized by an intramolecular hydrogen bond between the amino group and the phenyl ring. The observed conformations were examined in light of the Shallenberger-Acree-Kier molecular theory of sweet taste, and they align with the hypothesized criteria. Furthermore, the study illustrates how conformational relaxation can alter the equilibrium conformational distribution, resulting in the absence of certain conformers in the conformational landscape.

Disentangling the Conformational Space and Structural Preferences of Tetrahydrofurfuryl Alcohol Using Rotational Spectroscopy and Computational Chemistry.

The influence of the hydroxymethyl (CH2OH) group on the tetrahydrofuran (THF) ring structure was investigated by disentangling the gas phase conformational landscape of the sugar analogue tetrahydrofurfuryl alcohol (THFA). By combining rotational spectroscopy (6-20 GHz) and quantum chemical calculations, transitions corresponding to two stable conformers of THFA and their 13C isotopologues were observed and assigned in the rotational spectrum. The positions of the C atoms were precisely determined to unambiguously distinguish between nearly isoenergetic pairs of conformers that differ in their ring configurations: envelope (E) versus twist (T). The rotational spectrum confirms that the E ring geometry is favoured when the CH2OH fragment lies gauche (-) to the THF backbone (OCCO ~-60°) whereas the T form is more stable for the gauche (+) alignment of the substituent (OCCO ~+60°). The observed spectral intensities suggest that conformational relaxation of the THF geometry (E↔T) to the more stable form readily occurs within the pairs of g- and g+ conformers which is consistent with the low barriers (1.5-1.7 kJ mol-1) for conversion determined via transition state calculations. Insights into the intramolecular hydrogen bonding and other weak interactions stabilizing the lowest energy structures of THFA were derived and rationalized using non-covalent interaction analyses.

Interfacial molecular structure and orientation evolution of the polystyrene under confinement during annealing revealed by sum frequency generation vibrational spectroscopy

The geometrical confinement directly affects many crucial properties of polymer thin films by interfacial interactions. A key to understanding the role of these interfacial interactions is to specifically probe the confined interface at the molecular level and in situ. However, the direct and nondestructive detection of interfacial polymer structures under confinement is very difficult. In this study, specific interface-sensitive sum frequency generation (SFG) spectroscopy was applied to study the deuterated PS (d8-PS) film confined between hydrogenated poly (methyl methacrylate) (PMMA) films at the molecular level and in situ. The results showed that the ordering/orientation of the PS chain (backbone and phenyl group) evolved at the buried d8-PS/PMMA interface during annealing. The tilt angle of the PS phenyl group increased while the twist angle decreased with elevated annealing temperature. Both overall SFG ssp and ppp intensities decreased after annealing at 433 K for 24 h, indicating that PS chains entangled with or penetrated the PMMA chains at the confined interface. This study qualitatively and quantitatively revealed the interfacial structure and structural evolution of the PS chain confined between PMMA films in situ during annealing, which is beneficial to the molecular-level understanding of the interfacial chain conformational relaxation of polymers under confinement.

Molecular Simulation Study of the Kinetics and Mechanism of Micellization of Charged and Uncharged Block Copolymer in Aqueous Solution: Polystyrene-Block-Poly(acrylic acid) PS-b-PAA

The micellization kinetics, dynamics, and diffusional properties of poly(styrene)-block-poly(acrylic acid) copolymer chains in salt-free aqueous solution have been investigated as a function of the copolymer composition (XPS ) for the cases of un-ionized (charge density f = 0) and ionized PAA blocks (charge density f = 1), for the first time to our knowledge via atomistic molecular dynamic simulations. The micelle formation mechanism was inspected by tracking the population of unimers and clusters across the simulation trajectory; it confirmed that the asymmetric copolymer micelle formation followed a combined approach of unimer insertion and cluster fusion mechanisms, while symmetric micelle formation followed the unimer insertion method exclusively. Micelle formation took a longer time for copolymers having charged (ionized) PAA blocks (f > 0) and relatively short PS blocks (number fraction of PS repeat units in copolymer XPS < 0.5) due to the presence of a greater number of hydrophobic groups, in agreement with the micellization kinetics observed for model copolymer micelles via DPD (Dissipative Particle Dynamics) simulation studies in literature. The conformational dynamics were studied using the relaxation of backbone dihedral angles and radius of gyration, for the core and corona blocks, respectively, showed that the PS blocks relaxed slower as compared to the soluble PAA blocks in solution due to their hydrophobic nature. The conformational relaxation time increased linearly for the PS blocks and was invariant for the PAA blocks with respect to XPS. The interaction dynamics of the PS-b-PAA copolymer micelles studied via the relaxation times of the PAA-PAA inter-chain (τHB,PP) and PAA-water inter-molecular hydrogen bonds (τHB,PW) showed the increase of τHB,PP, and the decrease of τHB,PW in solution with the increase in XPS. The PAA-water H-bond relaxes slower at f = 1 than that at f = 0 due to the stronger affinity of ionized PAA units with water molecules. The diffusivity of the copolymer chains decreased exponentially with an increase in XPS value, which is in agreement with the theoretical and experimental observations described in the literature.

Optically Tunable Multistable Liquid Crystal Grating for Anti‐Counterfeiting through Multilayer Continuous Phase Analysis

AbstractOptically tunable liquid‐crystal (LC) gratings have remarkable applications in the field of image analysis for anti‐counterfeiting. However, existing tunable LC gratings suffer from limited adjustable ranges and weak stability. The spacing variability and accuracy of the grating cannot satisfy the demands of continuous analysis. This study presents a novel approach to anti‐counterfeiting through multilayer continuous phase analysis (MCPA) based on the continuous multistable states of the LC grating. This optically tunable LC grating featuring continuous multistable states is successfully prepared using a novel optically tunable chiral dopant, tetra(n‐hex‐azo), which exhibits an exceptionally slow conformational relaxation rate (half‐life: 78.02 h). By exposing the LC grating to ultraviolet irradiation with an intensity of 0.1054 mW cm−2, the fringe spacing can be continuously and widely tuned between 0 and 250 µm, which enhances the ultraslow conformational relaxation of tetra(n‐hex‐azo). Four representative spacings (50, 55, 60, and 65 µm) are selected to construct four‐layer MCPA gratings, enabling simultaneous decoding of a four‐layer latent image for the first time. The mechanism of the MCPA grating is investigated through control experiments and theoretical simulations. This study demonstrates a facile, precise, and efficient approach for complex information encryption and anti‐counterfeiting.

Computer-assisted discovery and evaluation of potential ribosomal protein S6 kinase beta 2 inhibitors

S6K2 is an important protein in mTOR signaling pathway and cancer. To identify potential S6K2 inhibitors for mTOR pathway treatment, a virtual screening of 1,575,957 active molecules was performed using PLANET, AutoDock GPU, and AutoDock Vina, with their classification abilities compared. The MM/PB(GB)SA method was used to identify four compounds with the strongest binding energies. These compounds were further investigated using molecular dynamics (MD) simulations to understand the properties of the S6K2/ligand complex. Due to a lack of available 3D structures of S6K2, OmegaFold served as a reliable 3D predictive model with higher evaluation scores in SAVES v6.0 than AlphaFold, AlphaFold2, and RoseTTAFold2. The 150 ns MD simulation revealed that the S6K2 structure in aqueous solvation experienced compression during conformational relaxation and encountered potential energy traps of about 19.6 kJ mol−1. The virtual screening results indicated that Lys75 and Lys99 in S6K2 are key binding sites in the binding cavity. Additionally, MD simulations revealed that the ligands remained attached to the activation cavity of S6K2. Among the compounds, compound 1 induced restrictive dissociation of S6K2 in the presence of a flexible region, compound 8 achieved strong stability through hydrogen bonding with Lys99, compound 9 caused S6K2 tightening, and the binding of compound 16 was heavily influenced by hydrophobic interactions. This study suggests that these four potential inhibitors with different mechanisms of action could provide potential therapeutic options.

Ultrafast excited state relaxation dynamics of pyran-based D-π-A systems: solvent polarity controls the triplet state.

The excited state relaxation dynamics of V-shaped D-π-A systems having 4H-pyranylidene appended barbituric acid as an acceptor and diphenylamine (TPAPBA) and diethyl amine (EAPBA) as donors were investigated using steady-state and time-resolved spectroscopy along with theoretical optimization. The steady-state photophysical characterization exhibited the bathochromic shift of the emission maximum (∼6400 cm-1) and large change in the dipole moment (∼24D) with an increase of solvent polarity, reflecting the occurrence of the intramolecular charge transfer state (ICT) in the excited state. The nanosecond and femtosecond transient absorption spectra of these derivatives in a non-polar solvent, toluene, reveal that the excited state relaxation pathway involving a local excited state (LE) decayed to ICT followed by the formation of a twisted ICT state by conformational relaxation, finally leading to the triplet state. The lack of observation of a triplet state in the polar solvent, acetonitrile, signifies that the relaxation dynamics of V-shaped triads in the excited state are influenced by the polarity of the solvent.

Ultrafast photophysics of para-substituted 2,5-bis(arylethynyl) rhodacyclopentadienes: thermally activated intersystem crossing.

2,5-Bis(phenylethynyl) rhodacyclopentadienes (RCPDs), as a type of Rh(iii) complex, exhibit unusually intense fluorescence and slow intersystem crossing (ISC) due to weak metal-ligand interactions. However, details on their ultrafast photophysics and ISC dynamics are limited. In this work, electronic relaxation upon photoexcitation of two substituted RCPDs with two -CO2Me (A-RC-A) or -NMe2/-CO2Me (D-RC-A) end groups are comprehensively investigated using femtosecond transient absorption spectroscopy and theoretical analysis. Upon ultraviolet and visible excitation, dephasing of vibrational coherence, charge transfer, conformation relaxation, and ISC are observed experimentally. By calculating the spin-orbit coupling, reorganization energy, and adiabatic energy gap of plausible ISC channels, semi-classical Marcus theory revealed the dominance of thermally activated ISC (S1 → T2) for both D-RC-A and A-RC-A, while S1 → T1 channels are largely blocked due to high ISC barriers. With weak spin-orbit coupling, such differences in plausible ISC channels are predominately tuned by energetic parameters. Singlet oxygen sensitization studies of A-RC-A provide additional insight into the excited-state behavior of this complex.

Dielectric Spectroscopy Studies of Conformational Relaxation Dynamics in Molecular Glass-Forming Liquids.

We review experimental results obtained with broadband dielectric spectroscopy concerning the relaxation times and activation energies of intramolecular conformational relaxation processes in small-molecule glass-formers. Such processes are due to the interconversion between different conformers of relatively flexible molecules, and generally involve conformational changes of flexible chain or ring moieties, or else the rigid rotation of planar groups, such as conjugated phenyl rings. Comparative analysis of molecules possessing the same (type of) functional group is carried out in order to test the possibility of assigning the dynamic conformational isomerism of given families of organic compounds to the motion of specific molecular subunits. These range from terminal halomethyl and acetyl/acetoxy groups to both rigid and flexible ring structures, such as the planar halobenzene cycles or the buckled saccharide and diazepine rings. A short section on polyesters provides a generalisation of these findings to synthetic macromolecules.

Reaction induced conformational change in polyindole: Polyindole/PVA film as biomimetic sensors of temperature and electrical energetic condition.

The influence of surrounding temperature and electrical energetic condition on the conformational movements (cooperative actuation) of polyindole is verified using a polyindole-coated polyvinyl alcohol (PIN/PVA) film. Chronopotentiometric studies revealsthat the consumed electrical energy during the reaction varies linearly with the change in working temperature. The influence of temperature on the reversible conformational movements of the polymer chain is related to the charge consumed during the reaction. The logarithmic dependence of reversible redox charge obtained from coulovoltammogram with inverse of temperature further proved the temperature sensing characteristics and the influence of temperature on the cooperative actuation of the PIN/PVA film. The conformational relaxation increases as the temperature increases through hosting higher number of counter anions with the solvent molecule. The extension of the redox reaction or charge consumption was found to decrease as the scan rate increases. The double logarithmic relation between the consumed redox charge and the scan rate has proved that the electrical energetic condition can influence the conformational movement or the extension of the redox reaction in a reversible manner. The results suggest that the PIN/PVA film can act as a biomimetic macro molecular sensor of working temperature and electrical energetic condition as biological muscles do.

Kinetics of Single-Wall Carbon Nanotube Coating Displacement by Single-Stranded DNA Depends on Nanotube Structure.

Time-resolved fluorescence spectroscopy has been used to study the displacement of adsorbed sodium dodecyl sulfate (SDS) from the surface of single-wall carbon nanotubes (SWCNTs) by short strands of single-stranded DNA. Intensity changes in near-infrared emission peaks of various SWCNT structures were analyzed following the addition of six different (GT)n oligomers (n from 3 to 20) to SDS-coated nanotube samples. There is a strong kinetic dependence on the oligomer length, with (GT)3 giving an initial rate more than 300 times greater than that of (GT)20. For shorter oligos in the (GT)n series, we observe an inverse dependence of the displacement rate on the SWCNT diameter, with SDS displaced from (6,5) more than twice as fast as from (8,7). However, this diameter dependence is reversed for oligos with more than six (GT) units. There is also a systematic dependence of the displacement rate on the nanotube chiral angle that is strongest for (GT)5, leading to a factor of ∼3 initial rate difference between (9,1) and (6,5) despite their identical diameters. To account for these findings, we propose a simple two-step kinetic model in which disruption of the original SDS coating is followed by conformational relaxation of ssDNA on the nanotube surface. The relaxation is relatively fast for ssDNA oligos shorter than 12 bp, making the first step rate-determining. Conversely, relaxation of the longer oligomers is slow enough that the second step becomes rate-determining.

Conformational Relaxation Dynamics of Poly(3-hexylthiophene) Photoexcited in Solution as Studied by Femtosecond Time-Resolved Stimulated Raman Spectroscopy in 1190-1550 nm Region.

When a conjugated polymer is photoexcited in solution, its effective conjugation length in the singlet exciton state often increases through the conformational relaxation of the polymer main chain and/or hopping of the excitation. We measured femtosecond time-resolved near-IR stimulated Raman spectra of poly(3-hexylthiophene) (P3HT) photoexcited in four organic solvents for understanding the dynamics of the exciton elongation through the conformational relaxation separately from that through the exciton hopping. In the ring CC stretch frequency region, a band appears at around 1415 cm-1 and decays, while a new band rises at around 1370 cm-1. The average time constant of the change is estimated to be 8.7-19 ps and correlated almost linearly with the viscosity of the solvents. These results suggest that the main chain of P3HT in the singlet exciton state relaxes from a twisted form to a planar form in the 0-100 ps range when it surmounts an activation barrier of 5.8-7.8 kJ mol-1, generated possibly by the steric effect of the hexyl side group. When the rise of the 1370 cm-1 band is analyzed in detail, it is reproduced with two exponential rise functions with time constants of 0-3.3 and 16-22 ps. The two rise components suggest that a portion of P3HT forms a cluster in solution, while the other portion of P3HT is isolated.

Acridin-9(10H)-one based thermally activated delayed fluorescence emitter for highly efficient green OLED

It is crucial for thermally activated delayed fluorescence (TADF) emitters to have both high photoluminescence quantum yield (PLQY) and high reverse intersystem crossing rate (kRISC). A novel TADF emitter, namely 3,6-bis(3,6-bis(diphenylamino)-9H-carbazol-9-yl)-10-phenylacridin-9(10H)-one (3,6-DPCz-AD), was designed by introducing N3,N3,N6,N6-tetraphenyl-9H-carbazole-3,6-diamine (DPCz) at 3,6-sites of the acceptor acridin-9(10H)-one (AD) by nucleophilic substitution. On the acridin-9(10H)-one ring, the sp2-hybridization of the 10-site N atom leads to high rigidity, which inhibited conformation relaxation of excited state to reduce non-radiative decay. The introduction of large conjugated diphenylamine groups at the 3,6-sites of carbazole not only facilitated the RISC by increasing intramolecular charge transfer and generating a low S1-T1 energy gap (ΔEST), but also enhanced the radiative transition by enlarging the highest occupied molecular orbital (HOMO) delocalization. As a result, even without the traditional highly distorted structure, 3,6-DPCz-AD exhibited strong TADF characteristics with high kRISC of 5.8 × 105 s−1, high kr of 3.4 × 107 s−1 and a high PLQY of 99% simultaneously. The green organic light-emitting diode (OLED) of 3,6-DPCz-AD showed both a maximum external quantum efficiency (EQEmax) of 30.1% and a power efficiency of 83.3 lm W−1. An EQE of 20.1% was still remained at a high brightness of 1000 cd m−2. This is one of the best performances for acridin-9(10H)-one based TADF emitters ever reported so far.

Light scattering study of intrachain conformational relaxation of hyperbranched polystyrene chains in a marginal solvent

So far, much less attention has been paid to the dynamic behavior of branched polymers under marginal solvent condition. This work reports the first study of the intrachain conformational relaxation of hyperbranched polystyrene (PS) chains under the marginal solvent condition in the dilute regime. Specifically, the solvents of ethyl acetate (EA) and toluene (Tol) are selected for comparison. By a combination of static and dynamic light scattering measurements, a few findings have been revealed: 1) the weight average of molar masses (Mw) of hyperbranched PS chains are determined to be 7.33 × 107 and 8.02 × 107 g/mol in Tol and EA, respectively, implying the single chain state under both solvent conditions; 2）the value of reduced first cumulant (Γ*) at very high q-regime, i.e., Γ*(∞), is determined to be around 0.026 ± 0.002 in EA, which is not only smaller than the smallest Γ*(∞) ≈ 0.052 ± 0.002 reported for linear chains in literature under theta and good solvent conditions, but also much smaller than the reported Γ*(∞) ≈ 0.033 ± 0.003 for hyperbranched chains in literature under good solvent condition, and the result implies the reduced hydrodynamic interactions. Although the excluded volume effect is relatively weak in the marginal solvent, the present study supports that the existence of weak binary interactions between segments still influence the conformational behavior significantly.

Alchemical Free Energy and Hamiltonian Replica Exchange Molecular Dynamics to Compute Hydrofluorocarbon Isotherms in Imidazolium-Based Ionic Liquids.

Ionic liquids (ILs) have shown promise for applications that leverage differential gas solubility in an IL solvent, e.g., gas separations. Although most available literature provides Henry's law constants, the ability to efficiently estimate full isotherms is important for engineering design calculations. Molecular simulation can be used as a tool to predict full isotherms of gas in ILs. However, particle insertions or deletions in a charge-dense IL medium and the sluggish conformational dynamics of ILs present two sampling challenges for these systems. We therefore devised a method that uses Hamiltonian replica exchange (HREX) molecular dynamics (MD) combined with alchemical free energy calculations to compute full solubility isotherms of two different hydrofluorocarbons (HFCs) in imidazolium-based IL binary mixtures. This workflow is significantly faster than the Gibbs ensemble Monte Carlo (GEMC) simulations which fail to deal with the slow conformational relaxation caused by the sluggish dynamics of ILs. Multiple free energy estimators, including thermodynamic integration, free energy perturbation, and multistate Bennett acceptance ratio method, provided consistent results. Overall, the simulated Henry's law constant, isotherm curvature, and solubility trends match experimental results reasonably well. We close by calculating the full solubility isotherms of two HFCs in IL mixtures that have not been reported in the literature, demonstrating the potential of this method to be used for solubility prediction and setting the stage for future computational screening studies that search for the "best" IL to separate azeotropic HFC mixtures.

Opacity dependence of transverse flow, preequilibrium, and applicability of hydrodynamics in heavy-ion collisions

We evaluate the full opacity dependence of collective flow in high-energy heavy-ion collisions within a microscopic kinetic description based on the Boltzmann equation in the conformal relaxation time approximation. By comparing kinetic theory calculations to hydrodynamic and hybrid simulations for an average initial state, we point out shortcomings and inaccuracies of hydrodynamic models and present modified simulation setups to improve them.

Simulation studies on the dynamic heterogeneity of organic ionic plastic crystals

AbstractOrganic ionic plastic crystals (OIPCs) are one of promising solid‐state electrolytes (SSEs) for all‐solid‐state batteries. OIPCs consist of organic ions that form crystalline solid phases. It is a challenging but critical task in the development of SSEs to improve the ion conductivity of lithium ions in such crystalline solid phases. We discuss our recent simulation studies on the transport mechanism of ions in OIPCs and show that the dynamic heterogeneity should be a key to the transport mechanism. We aim to show that both translational and rotational dynamic heterogeneities should play an important role in understanding the ionic conductivity in SSEs. We found from our simulations that the introduction of dopants and defects into OIPCs facilitated both the dynamic heterogeneity and the ion conductivity significantly. We also found that the polarizability of matrix organic ions could contribute to the rotational and conformational relaxations of organic ions in OIPCs.