Excited State Conformations Research Articles

Regulating IL-2 immune signaling function via a core allosteric structural network.

NMR and molecular dynamics simulations revealed distinct conformational dynamics and allosteric networks in computationally re-designed IL-2 superkines compared to wild-type IL-2, despite their similar crystal structures.The superkines S1 and S15 exhibit altered sampling of excited state conformations at an intermediate timescale, with slower conformational exchange rates compared to wild-type IL-2.A rationally designed mutation (L56A) in the S1 superkine's core allosteric network partially reverted its dynamics, receptor binding affinity, and T cell signaling behavior towards that of wild-type IL-2.Our study demonstrates that IL-2 core dynamics play a critical role in receptor binding and signaling function, providing a foundation for engineering more selective IL-2-based immunotherapies.

Solvent-Dependent Emissions Properties of a Model Aurone Enable Use in Biological Applications.

Fluorophores are powerful visualization tools and the development of novel small organic fluorophores are in great demand. Small organic fluorophores have been derived from the aurone skeleton, 2-benzylidenebenzofuran-3(2H)-one. In this study, we have utilized a model aurone derivative with a methoxy group at the 3' position and a hydroxyl group at the 4' position, termed vanillin aurone, to develop a foundational understanding of structural factors impacting aurone fluorescence properties. The fluorescent behaviors of the model aurone were characterized in solvent environments differing in relative polarity and dielectric constant. These data suggested that hydrogen bonding or electrostatic interactions between excited state aurone and solvent directly impact emissions properties such as peak emission wavelength, emission intensity, and Stokes shift. Time-dependent Density Functional Theory (TD-DFT) model calculations suggest that quenched aurone emissions observed in water are a consequence of stabilization of a twisted excited state conformation that disrupts conjugation. In contrast, the calculations indicate that low polarity solvents such as toluene or acetone stabilize a brightly fluorescent planar state. Based on this, additional experiments were performed to demonstrate use as a turn-on probe in an aqueous environment in response to conditions leading to planar excited state stabilization. Vanillin aurone was observed to bind to a model ATP binding protein, YME1L, leading to enhanced emissions intensities with a dissociation equilibrium constant equal to ~ 30 µM. Separately, the aurone was observed to be cell permeable with significant toxicity at doses exceeding 6.25 µM. Taken together, these results suggest that aurones may be broadly useful as turn-on probes in aqueous environments that promote either a change in relative solvent polarity or through direct stabilization of a planar excited state through macromolecular binding.

Excited States of apo-Guanidine-III Riboswitch Contribute to Guanidinium Binding through Both Conformational and Induced-Fit Mechanisms.

Riboswitches are mRNA segments that regulate gene expression through conformational changes driven by their cognate ligand binding. The ykkC motif forms a riboswitch class that selectively senses a guanidinium ion (Gdm+) and regulates the downstream expression of proteins which aid in the efflux of excess Gdm+ from the cells. The aptamer domain (AD) of the guanidine-III riboswitch forms an H-type pseudoknot with a triple helical domain that binds a Gdm+. We studied the binding of Gdm+ to the AD of the guanidine (ykkC)-III riboswitch using computer simulations to probe the specificity of the riboswitch to Gdm+ binding. We show that Gdm+ binding is a fast process occurring on the nanosecond time scale, with minimal conformational changes to the AD. Using machine learning and Markov-state models, we identified the excited conformational states of the AD, which have a high Gdm+ binding propensity, making the Gdm+ binding landscape complex exhibiting both conformational selection and induced-fit mechanisms. The proposed apo-AD excited states and their role in the ligand-sensing mechanism are amenable to experimental verification. Further, targeting these excited-state conformations in discovering new antibiotics can be explored.

Synergetic Conformational Regulations in Ground and Excited States for Realizing Stimulus-Responsive and Wide-Tuning Room-Temperature Phosphorescence.

Understanding the changes of molecular conformations is crucial for realizing multiple emissive triplet states in room-temperature phosphorescence (RTP) materials. In this work, we report two molecules, 4,4'-dimethylbenzil (DMBZ) and 4,4'-di-tert-butylbenzil (DBBZ) with conformation-dependent luminescence, and demonstrate that stimulus-responsive and wide-tuning RTP emissions can be realized via synergetic conformational regulations in ground and excited states. Due to conformational changes, DMBZ and DBBZ show abundant RTP variations upon external stimuli, including light, force, heat, and fumigation. Notably, DBBZ exhibits multiple conformational changes in both ground and excited states, which endow DBBZ with multiple emissive states and unique stimulus-responsive behaviors. DBBZ presents multiple phase transitions between the supercooled liquid state and different solid states accompanied by different phosphorescence transitions, in which the excited-state conformations are effectively regulated. Moreover, wide-range RTP regulations (between cyan, green, and yellow) are realized in both single component and host-guest systems of DBBZ, showing potential applications in temperature sensing, multicolor dynamic displays, and information encryption. These results may provide new visions for understanding the complicated conformational changes in the aggregated state, as well as unique insights into the relationship between molecular conformations, RTP emissions, and stimulus responsiveness.

An elastic organic crystal with multilevel stimuli-responsive room temperature phosphorescence

•Elastic organic RTP crystal with multilevel stimuli responsiveness was first reported •Highest RTP quantum yield of 25.1% was recorded in elastic organic RTP crystal •Modulation of RTP was realized via the transition of excited state conformation •RTP single to double emission under external stimuli in single-component system In this work, we report a series of single-component molecules crystals named dialkyl 4,4′-oxalyldibenzoate (n-BZ) with both efficient room temperature phosphorescence (RTP) emission, multilevel stimuli responsiveness, and elasticity or flexibility. The crystalline n-BZ will change from original RTP single emission to RTP dual emission after grinding or thermal annealing (TA). Interestingly, the emission wavelength difference between the RTP dual-emission peaks after grinding or TA reaches 82 nm with emission color changes from cyan blue to orange. In addition, to our knowledge, the largest RTP quantum yield of 25.1% (6-BZ) has been achieved as the highest recorded for organic RTP elastic crystals. Through a series of experiments and theoretical calculations, we demonstrate that the multilevel stimuli responsiveness of n-BZ originates from the transition of excited state conformation and its elasticity from many weak intermolecular interactions, which will provide a molecular design and construction strategy for organic stimuli-responsive RTP materials. In this work, we report a series of single-component molecules crystals named dialkyl 4,4′-oxalyldibenzoate (n-BZ) with both efficient room temperature phosphorescence (RTP) emission, multilevel stimuli responsiveness, and elasticity or flexibility. The crystalline n-BZ will change from original RTP single emission to RTP dual emission after grinding or thermal annealing (TA). Interestingly, the emission wavelength difference between the RTP dual-emission peaks after grinding or TA reaches 82 nm with emission color changes from cyan blue to orange. In addition, to our knowledge, the largest RTP quantum yield of 25.1% (6-BZ) has been achieved as the highest recorded for organic RTP elastic crystals. Through a series of experiments and theoretical calculations, we demonstrate that the multilevel stimuli responsiveness of n-BZ originates from the transition of excited state conformation and its elasticity from many weak intermolecular interactions, which will provide a molecular design and construction strategy for organic stimuli-responsive RTP materials.

Photoexcitation-Induced Assembly: A Bottom-Up Physical Strategy for Driving Molecular Motion and Phase Evolution

ConspectusIn the field of molecular assembly, photodriven self-assembly is a smart and crucial strategy to regulate the molecular orderliness, multiscale structure, and optoelectronic properties. Traditionally, photodriven self-assembly is based on photochemical processes, through molecular structural change induced by photoreactions. Despite great progress in the photochemical self-assembly, there still exists disadvantages (e.g., the photoconversion rate never reaches 100% with the possible side reactions). Therefore, the photoinduced nanostructure and morphology are often difficult to predict due to insufficient phase transition or defects. In contrast, the physical processes based on photoexcitation are straightforward and can fully utilize photons to avoid the drawbacks of photochemistry. The photoexcitation strategy excludes the change of molecular structure, only utilizing the molecular conformational change from the ground state to excited state. Then, the excited state conformation is employed to drive molecular movement and aggregation, further promoting the synergistic assembly or phase transition of the entire material system. The regulation and exploration of molecular assembly upon photoexcitation can open up a new paradigm to deal with the "bottom-up" behavior and develop unprecedented optoelectronic functional materials.This Account starts with a brief introduction to the problems faced by photocontrolled self-assembly and presents the photoexcitation-induced assembly (PEIA) strategy. Then, we focus on exploring PEIA strategy based on persulfurated arenes as the prototype. The molecular conformational transition of persulfurated arenes from the ground state to the excited state is conducive to the formation of intermolecular interactions, successively driving molecular motion, aggregation, and assembly. Next, we describe our progress in exploring PEIA of persulfurated arenes at the molecular level and then demonstrate that the PEIA of persulfurated arenes can synergistically drive molecular motion and phase transition in various block copolymer systems. Moreover, we provide the potential applications of PEIA in dynamic visual imaging, information encryption, and surface property regulation. Finally, an outlook on further development of PEIA is prospected.

AIEgens Based on Dehydroabietic Acid Triarylamine and Tetraphenylethene: Synthesis, Luminescence Regulation, and Application in Cell Imaging

Biomass-derived luminogens with strong emission capacity in the aggregated or solid state are in demand because of their renewability, sustainability, and biocompatibility. Herein, we synthesized aggregation-induced emission luminogens (AIEgens) based on dehydroabietic acid triarylamine (DTPA) derived from natural rosin, and their spectral properties, molecular conformation, electron distribution, and energy levels were explored to elucidate the effect and mechanism of structure regulation. The prepared AIEgens exhibited different emission wavelengths and luminescence efficiencies attributed to the conjugation degree and molecular motion. DTPA–mTPE with a meta-linkage mode exhibits blue emission with highest quantum yield among all compounds. DDPA–pTPE, formed by DTPA sharing a phenyl ring with TPE, redshifts visibly from 488 to 508 nm, attributed to the narrower excited-state energy gap. Introducing a dehydroabietic acid skeleton creates a rigid molecular conformation, and a highly twisted molecular conformation is unfavorable to stabilize the excited-state molecular conformation and reduces luminous efficiency. Finally, DTPA–pTPE, DTPA–mTPE, 2DTPA–mTPE, and DDPA–pTPE were prepared nanoparticles, which exhibited low cellular toxicity and excellent cell imaging results. This work offers new insights into the synthesis of rosin-based AIEgens, facilitating the design of naturally derived luminescent materials.

Photophysics of the red-form Kaede chromophore.

The green fluorescent protein (GFP) drove revolutionary progress in bioimaging. Photoconvertible fluorescent proteins (PCFPs) are an important branch of the FP family, of which Kaede is the prototype. Uniquely, PCFPs can be permanently switched from green to red emitting forms on UV irradiation, facilitating applications in site-specific photolabelling and protein tracking. Optimisation and exploitation of FPs requires understanding of the photophysical and photochemical behaviour of the chromophore. Accordingly, the principal GFP chromophore has been the subject of intense experimental and theoretical investigation. In contrast, the photophysics of the red emitting PCFP chromophore are largely unstudied. Here we present a detailed investigation of the excited-state properties of the Kaede chromophore in solution, utilising steady state measurements, ultrafast time-resolved electronic and vibrational spectroscopies, and electronic structure theory. Its excited state dynamics are very different to those of the parent GFP. Most remarkably, the PCFP chromophore has highly complex wavelength-dependent fluorescence decays and a mean lifetime an order of magnitude longer than the GFP chromophore. Transient electronic and vibrational spectroscopies suggest that these dynamics arise from a range of excited-state conformers that are spectrally and kinetically distinct but chemically similar. These conformers are populated directly by excitation of a broad thermal distribution of ground state structures about a single conformer, suggesting an excited-state potential surface with several minima. Temperature-dependence confirms the existence of barriers on the excited-state surface and reveals the radiationless decay mechanism to be internal conversion. These experimental observations are consistent with a model assuming a simple ground state potential energy surface accessing a complex excited state possessing multiple minima.

Highly Emissive Luminogens in Both Solution and Aggregate States

Highly Emissive Luminogens in Both Solution and Aggregate States

Two-state model for the SmAP_{R} phase with randomized layer polarization exhibited by some compounds with bent-core molecules.

One of the unusual liquid crystalline phases exhibited by some compounds with bent-core (BC) molecules is designated as SmAP_{R}, in which transverse polarization (P) of smectic layers with upright molecules has a random orientational distribution. Most of such compounds undergo a transition to the SmAP_{A} phase with antiferroelectric order of adjacent layers as the temperature is lowered. Second harmonic studies have shown that the medium consists of polarized domains with only a few hundred molecules, the number increasing at lower temperatures. This is in contrast to the random orientations of entire layers predicted by a few phenomenological models which have been proposed for the SmAP_{R} phase. In this paper we show that the two-state model, developed earlier by us to describe modulated phases found in compounds with BC molecules, can successfully account for all the experimental results on the SmAP_{R} phase. It is proposed that polarized domains which are made of ground state conformers, with a large bend of the aromatic cores, nucleate as circular disks in a first order transition from the isotropic phase. Excited state conformers (with a smaller bend) freely rotate about their long axes and surround the disks. The polarization in the disk has a spontaneous splay distortion which generates a texture with an expelled center of a partial disclination. The interdisk electrostatic energy is lower than the thermal energy and the disks are subject to significant rotational fluctuations, resulting in the uniaxial symmetry of the medium. Calculated equilibrium properties of the medium as functions of temperature and electric field reflect the trends seen in experiments. The model overestimates properties such as the radius of the disks as the transition to a lower temperature uniform phase is approached, and physical arguments are given to show that interlayer interactions ignored in the model become important in that regime, and should be included for an improved description of the medium.

Twisted Intramolecular Charge Transfer—Aggregation-Induced Emission Fluorogen with Polymer Encapsulation-Enhanced Near-Infrared Emission for Bioimaging

Fluorescence probes with strong near-infrared (NIR) emission and water solubility are considered useful visualization tools for localization marking as well as investigating cell migration and tran...

High-contrast mechanochromic fluorescence from a highly solid-state emissive 2-(dimesitylboryl)phenyl-substituted [2.2]paracyclophane

A highly solid-state emissive triarylborane-based [2.2]paracyclophane exhibits high-contrast mechanochromic fluorescence owing to the alternating excited state conformations formed in the crystalline and amorphous phases.

Dynamic adjustment of emission from both singlets and triplets: the role of excited state conformation relaxation and charge transfer in phenothiazine derivates

Dynamic adjustment of emission behaviours by controlling the extent of twisted intramolecular charge transfer character in excited state.

Excited-state conformation capture by supramolecular chains towards triplet-involved organic emitters

Nowadays, the development of triplet-involved materials becomes a hot research topic in solid-state luminescence fields. However, the mechanism of triplet-involved emission still remains some mysteries to conquer. Here, we proposed a new concept of excited-state conformation capture for the constructions of different types of triplet-involved materials. Firstly, excited-state conformation could be trapped by supramolecular chains in crystal and form a new optimum excited-state structure which is different from that in solution or simple rigid environment, leading to bright thermally activated delayed fluorescence (TADF) emission. Based on excited-state conformation capture methodology, next, we obtained room-temperature phosphorescence (RTP) by introducing Br atoms for the enhancement of intersystem crossing. It could be concluded from experimental results that TADF may originate from aggregate effect while RTP may derive from monomers. Finally, heavy-atom free RTP and ultra RTP were achieved by eliminating aggregate effect. This work could not only extend the design methodology of triplet-involved materials but also set clear evidences for the mechanism of triplet-involved emissions.

2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states.

2′-O-Methyl (Nm) is a highly abundant post-transcriptional RNA modification that plays important biological roles through mechanisms that are not entirely understood. There is evidence that Nm can alter the biological activities of RNAs by biasing the ribose sugar pucker equilibrium toward the C3′-endo conformation formed in canonical duplexes. However, little is known about how Nm might more broadly alter the dynamic ensembles of flexible RNAs containing bulges and internal loops. Here, using NMR and the HIV-1 transactivation response (TAR) element as a model system, we show that Nm preferentially stabilizes alternative secondary structures in which the Nm-modified nucleotides are paired, increasing both the abundance and lifetime of low-populated short-lived excited states by up to 10-fold. The extent of stabilization increased with number of Nm modifications and was also dependent on Mg2+. Through phi-value analysis, the Nm modification also provided rare insights into the structure of the transition state for conformational exchange. Our results suggest that Nm could alter the biological activities of Nm-modified RNAs by modulating their secondary structural ensembles as well as establish the utility of Nm as a tool for the discovery and characterization of RNA excited state conformations.

Ab initio and NBO studies of methyl internal rotation in 1-methyl-2(1H)-quinolinone: effect of aromatic substitution to 1-methyl-2(1H)-pyridone.

1-methyl-2(1H)-quinolinone (MeQone) forms the framework of several hundred alkaloid molecules both natural and synthetic being used for various biological applications. From chemical structure point of view, the molecules can also be seen as an aromatic ring fused to 1-methyl-2(1H)-pyridone (1-MPY). In this work, we present theoretical investigations on internal rotation of methyl group in MeQone in light of 1-MPY. We looked into the change in the three-fold (V3) methyl internal rotation barrier resulted from the aromatic ring substitution to 1-MPY. The V3 term in two molecules were calculated using density functional theory and Hartree-Fock theory with different basis sets. MeQone has calculated V3 term (in S0 state) three times higher in magnitude compared with that of 1-MPY. The role of aromatic substitution in increase of V3 term is investigated using natural bond orbital (NBO) analyses. In the NBO analysis, it is found that the aromatic ring as highly delocalized π-system lowers the magnitude of hyperconjugation energy in MeQone compared with 1-MPY. This is due to the extension of delocalization of π-electrons to pyridone ring which lowers the orbital overlap. However, the Lewis energy increases substantially and make the overall barrier energy higher in MeQone compared with 1-MPY. From our study, we conclude that in the molecules such as 1-MPY and MeQone where the methyl group has two single bonds vicinal to it, the overall hyperconjugation energy is always barrier forming with nonlocal interactions playing significant role. Also, the Lewis energy plays the decisive role in barrier formation, and its magnitude can be tuned by tuning the π-electron delocalization. We have also looked into the change in methyl group conformation upon electronic excitation to S1 state. In 1-MPY, the methyl group rotated by 60° upon excitation whereas in MeQone, there was no conformational change. Strong π*-σ* interaction in LUMO in top-of-barrier conformation is responsible for the change in the methyl group conformation in 1-MPY, whereas same π*-σ* interaction in LUMO of minimum energy conformation results in unchanged excited state conformation in MeQone. Graphical abstract.

A two-state model for the modulated B7 liquid crystalline phase exhibited by bent-core molecules

Liquid crystals (LC) made of bent-core (BC) organic molecules have been intensively studied over the past two decades. The B7 LC consists of smectic layers in which tilted molecules have an in-plane polar packing, the polarization vector (P) having a splay distortion forming stripes of tens of nanometers in width, and undulated layers giving rise to 2D rectangular or oblique lattices. The prevailing phenomenological theory attributes this structure to a strong coupling between molecular tilt in the layers and divP. Based on our recent studies on other phases exhibited by BC molecules, we propose a new model in which the physical origin of the stripes arises from a minority (~10%) of the BC molecules having less bent excited state (ES) conformers which can freely rotate about their long axes, and aggregate to form smectic C type walls, in which the tilt angle is relatively small. The more bent ground state (GS) conformers with polar packing in turn form the splayed structure between such walls to lower the free energy. The mismatch in the layer spacing between the domains with ES and GS conformers generates the structures in the B7 phase described above. The model predicts a weak first order transition from B7 to the uniform B2 phase as the temperature is lowered, as experimentally observed in some compounds. We show that the observed slow increase of the stripe width in the LC to micrometer dimensions in free standing films can be attributed to changes in the physical parameters by chemical degradation and absorption of ions by the exposed polarized layers. We also describe different possible structures of the undulated layers, including a stacking of racemic pairs of SmCaPF layers within the stripes. Some possible methods of testing the model are also indicated.

Exploiting singlet excited state conformation for rational design of highly efficient photoinduced electron transfer molecules.

In spite of the pivotal role of excited state electronic structures as regulation of photoinduced electron transfer (PET) process, the effect of excited state conformation on PET remains elusive. Here we exploit distinguishable emission characters of trans and cis singlet excited states of donor-acceptor-donor ensemble MTPAAZO to reveal that its PET efficiency and rate are closely depended on its singlet excited state conformation. The PET process occurs solely in cis conformation of MTPAAZO singlet excited states. Novel molecule (MTPA)2Ab as-designed with similar structure of MTPAAZO cis singlet excited states shows high PET efficacy and rate, leading to long-lived CS states. Our findings enable the rational design of the novel molecules with highly efficient PET process suitable for charge separation applications.

Photophysical, electrochemical and flexible organic resistive switching memory device application of a small molecule: 7,7-bis(hydroxyethylpiperazino) dicyanoquinodimethane

Abstract Utilization of Hydroxyethyl piperazine in a straightforward reaction with tetracyanoquinodimethane (TCNQ) produced a unique multifunctional molecular material 7,7-bis(Hydroxyethyl piperazino)dicyanoquinodimethane (BHEPDQ) exhibiting fluorescence, electrochemical property and capability of organic resistive switching (RS) memory device application. Obtained molecular material has been characterized by various spectroscopic and single crystal X-ray diffraction techniques. Fluorescence decay study in solid revealed single excited state conformation with life time ~1.26 ns. The energy levels were derived from the cyclic voltammetry and the electrochemical band gap was found to be 2.76 eV, good agreement with the theoretical band gap (2.75 eV). Flexible Al/BHEPDQ/ITO/PET RS non-volatile memory device was fabricated and different electrical performances were tested, which demonstrated excellent switching property. The SET/RESET voltage was found to be 2.26 V/– 2.88 V and the device offered high retention without any distortion. The effect of convex (upward bend) and concave (downward bend) bending on the resistive switching behavior of the same device was also investigated. The devices on a flexible platform under the application of a strain through different bending conditions exhibit no degradation on the electrical properties and the obtained results also matched well with the device under no stress, demonstrates its high reliability and ability for practical flexible electronic applications. The memory operations were also explained employing a proposed band diagram and transport studies were explicated to have the better insight of the obtained electrical performances. This work offers a new approach towards the realization of a novel organic material and its integration for efficient flexible memory device applications.

Simple model for the stripe phase in compounds with bent-core molecules which exhibit a lower-temperature ferroelectric smectic-A phase.

Bent-core (BC) molecules usually exhibit polar packing in smectic layers in which the long or bow axes tilt with respect to the layer normal. In many compounds, the tilt angle goes to zero, and typically the polarization (P) of neighboring layers has an antiferroelectric order (SmAP_{AF}). A careful molecular engineering has led to the discovery of the ferroelectric SmAP_{F} phase in a few BC compounds. Detailed experimental studies [Zhu et al., J. Am. Chem. Soc. 134, 9681 (2012)10.1021/ja3009314] have shown that one of the compounds undergoes a weak first order transition to a striped phase (SmAP_{Fmod}), in which the repolarization switching occurs at a threshold electric field, the latter increasing with temperature. The main optical birefringence of the SmAP_{Fmod} phase increases rapidly with the field at lower temperatures of its range. A small (<10%) fraction of the BC molecules can be expected to have less bent conformations in excited states (ESs), and we argue that the ES conformers rotate freely about the bow axes, and aggregate to form regions without any polar order to gain rotational entropy. In turn, a favorable divP term leads to the formation of stripes in the polarized regions made of ground state conformers. Based on this physical picture, we develop a simple phenomenological model to reproduce all the experimental trends qualitatively. In sample cells with insulating layers neighboring stripes prefer to have an antiparallel orientation of the mean P direction. The dielectric constant of the stripe phase increases with a dc bias electric field, a trend which is opposite to that in other ferroelectric liquid crystals.