Molecular Conformational Changes Research Articles

Photo-triggered Phase Transition of Crystals and Photoactuation.

Photo-triggered phase transition is a new type of phase transition in which a photochromic crystal with a thermal phase transition transforms into an identical high-temperature phase in a temperature region lower than the thermal phase transition temperature upon light irradiation. Here, we report a second crystal that exhibits a photo-triggered phase transition, thereby demonstrating that the photo-triggered phase transition is a general phenomenon that occurs in crystals. When the chiral salicylidenephenylethylamine crystal was irradiated with ultraviolet (UV) light, the photo-triggered phase transition occurred in the temperature range -30 to -10°C. The photo-triggered phase transition is induced by local stress due to trans-keto molecules produced by photoisomerization near the irradiated surface. Crystal cantilevers exhibited stepwise bending by the combination of the photo-triggered phase transition and photoisomerization. Alternate irradiation with UV and visible light achieved locomotion of single crystals driven by repeated stepwise bending. Finally, a detailed comparison of photo-triggered and non-photo-triggered phase transition crystals revealed that a sufficient molecular conformation change in affordable crystal voids, smooth photoisomerization, and most likely a chiral molecular arrangement are required for inducing the photo-triggered phase transition.

Effects of different protein cross-linking degrees on physicochemical and subsequent thermal gelling properties of silver carp myofibrillar proteins sol subjected to freeze-thaw cycles

Knowledge regarding the denaturation process and control methods for depolymerized sol-state myofibrillar proteins (MPs) during freezing remains scant. This study investigated the effects of protein cross-linking treatment before freezing on physicochemical and subsequent gelation properties of MPs sol subjected to freeze-thaw (F-T) cycles. Results indicated that after five F-T cycles, cross-linked MPs sols showed increased high molecular weight polymers and bound water (T21a and T21b) mobility, suggesting enhanced protein-protein interactions at the expense of protein-water interactions. Upon heating after F-T cycles, gels formed from cross-linked sols exhibited significantly higher hardness, springiness, and cooking loss (P < 0.05), alongside more contracted gel networks. Correlation analysis revealed that the formation and properties of thermal gel after freezing closely relate to changes in molecular conformation and chemical bonds of cross-linked MPs sol during freezing. This study provides new insights into regulating the freezing stability and post-thawed thermal processing properties of sol-based surimi products.

An adaptive biomolecular condensation response is conserved across environmentally divergent species

Cells must sense and respond to sudden maladaptive environmental changes—stresses—to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide a remarkable view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein—a core marker of stress granules—condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.

Polarization-resolved surface-enhanced infrared spectra with nanosensors based on self-organized gold nanorods

Biosensors are becoming ubiquitous in the study of biomolecules, as, by modifying shape size and environment of metallic nanostructures it is now possible to engineer the field so to monitor subtle transient changes in molecular conformation at the level of a single biolayer. In this paper we present a first step towards a polarization-resolved study of light-induced conformational changes of transmembrane proteins. We exploit a platform of self-organized gold nanorods on SiO2 substrates to enhance the infrared reflection absorption spectroscopy and to perform difference spectroscopy on a light-sensitive transmembrane protein with simultaneous visible light illumination from the backside of the chip. The broad size distribution of nanorods allows us to probe with high sensitivity the modifications of the vibrational peaks over the entire fingerprint region. We show that it is possible to identify dissimilarities in the difference spectra, which in turn implies that we are monitoring over a broadband spectrum not only the chemical bonds with the dipole moment aligned orthogonally to our substrate/nanorod surface but also those with different orientation.

Probing cell metabolism using the two-photon excitation autofluorescence lifetime of tryptophan.

Compared to intensity detection, fluorescence lifetime has the advantage of being unaffected by variations in excitation intensity, fluorophore concentration, or attenuation due to biological absorption and scattering. In this Letter, to the best of our knowledge, we present the use of the two-photon excitation autofluorescence lifetime imaging of tryptophan (TRP) to probe cell metabolism for the first time. Tests of pure chemical samples showed that the fluorescence lifetime of TRP was highly sensitive to changes in molecular conformation and the environment. In in vitro cell experiments, we successfully utilized the fluorescence lifetime of TRP to distinguish tumor cells from healthy cells, track the therapeutic effect of the tumor immunotherapy drug 1-MT for HeLa cells, and monitor cells in response to carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced cell apoptosis. These results reveal that the two-photon excitation autofluorescence lifetime of TRP could be a sensitive natural probe of cell metabolism in living cells.

Understanding the AIE phenomenon of nonconjugated rhodamine derivatives via aggregation-induced molecular conformation change

The bottom-up molecular science research paradigm has greatly propelled the advancement of materials science. However, some organic molecules can exhibit markedly different properties upon aggregation. Understanding the emergence of these properties and structure-property relationship has become a new research hotspot. In this work, by taking the unique closed-form rhodamines-based aggregation-induced emission (AIE) system as model compounds, we investigated their luminescent properties and the underlying mechanism deeply from a top-down viewpoint. Interestingly, the closed-form rhodamine-based AIE system did not display the expected emission behavior under high-viscosity or low-temperature conditions. Alternatively, we finally found that the molecular conformation change upon aggregation induced intramolecular charge transfer emission and played a significant role for the AIE phenomenon of these closed-form rhodamine derivatives. The application of these closed-form rhodamine-based AIE probe in food spoilage detection was also explored.

Total variation denoising-based method of identifying the states of single molecules in break junction data

Break junction (BJ) measurements provide insights into the electrical properties of diverse molecules, enabling the direct assessment of single-molecule conductances. The BJ method displays potential for use in determining the dynamics of individual molecules, single-molecule chemical reactions, and biomolecules, such as deoxyribonucleic acid and ribonucleic acid. However, conductance data obtained via single-molecule measurements may be susceptible to fluctuations due to minute structural changes within the junctions. Consequently, clearly identifying the conduction states of these molecules is challenging. This study aims to develop a method of precisely identifying conduction state traces. We propose a novel single-molecule analysis approach that employs total variation denoising (TVD) in signal processing, focusing on the integration of information technology with measured single-molecule data. We successfully applied this method to simulated conductance traces, effectively denoise the data, and elucidate multiple conduction states. The proposed method facilitates the identification of well-defined plateau lengths and supervised machine learning with enhanced accuracies. The introduced TVD-based analytical method is effective in elucidating the states within the measured single-molecule data. This approach exhibits the potential to offer novel perspectives regarding the formation of molecular junctions, conformational changes, and cleavage.

Efficient microwave-assisted synthesis of 1-hexylpyridin-1-ium bromide: Anion exchange to acetate and fundamentals tools to probe its interaction with RuCl3

The study presents a robust and efficient method for synthesizing high-purity 1-hexylpyridin-1-ium acetate (1-HP-Ac), a room-temperature ionic liquid (RTIL), using microwave synthesis. The study also explores its interaction with ruthenium trichloride (RuCl3). Initially, we employed classical solvothermal methods to obtain 1-hexypyridin-1-ium bromide (1-HP-Br), a precursor for 1-HP-Ac. Issues related to impurity and time constraints necessitated a transition to microwave-assisted synthesis, which emerged as an eco-friendly, energy-efficient approach. Microwave synthesis proved superior by delivering shorter reaction times (30 min), higher yields, and eliminating the need for solvents or inert atmospheres. Various characterization techniques (1H NMR, 13C NMR, FTIR, TGA, and HRMS) and matching quantum mechanical NMR predictions confirmed the successful synthesis of the hexylpyridinium cation and anion exchange transforming 1-HP-Br into its acetate form. The interaction between the synthesized RTIL and RuCl3 was monitored through NMR-based titrations and molecular dynamics (MD) modeling. The study explored the effects of increasing amounts of either RTIL or RuCl3 with the critical inflection point at a 1:2 ratio of 1-HP-Ac to RuCl3 for effective interactions and potential changes in average molecular conformation. Specifically, examining Karplus J-coupling constants provided information about dihedral angles within 1-HP-Ac. The data suggested that RuCl3 has a discernible influence on these angles, particularly for aliphatic protons. With thermal stability up to 200 °C, 1-HP-Ac is a fitting candidate for high-temperature reactions. MD simulation quantifies the solvation environment created by the IL as well as elucidates interactions of 1-HP-Ac with the RuCl3 crystal structure. The insights gained from our research into 1-HP-Ac's interaction with RuCl3, combined with the efficiency of microwave-assisted synthesis, open new avenues for further studies in catalysis, material science, and related fields..

Pressure-induced luminescence evolution of 3,3′-diamino-4,4′-azofurazan: Role of restricting chemical bond vibration and conformational modification

The luminescence and electronic structure of 3,3′-Diamino-4,4′-azofurazan (DAAzF) were studied under high pressure conditions through experimental and calculation approaches. The transition of π* → π was primarily responsible for DAAzF's broad light emission. Upon applying pressure to DAAzF, high-pressure-stiffened hydrogen-bond interactions enable the restriction of the stretching vibration of NH2 group. The reduced energy loss through nonradiative rotational relaxation and molecular motions lead to a ∼20 times luminescent enhancement of DAAzF from 1 atm to 8.9 GPa. With the further strengthening of interlayer hydrogen bond interactions at higher pressure, the deviation of hydrogen atoms in amino groups from the molecular plane lessens the radiation transition efficiency. In addition, the bending of the C–C–N=N bond further leads to molecular conformation changes at approximately 20.7 GPa, which induces an abrupt redshift and moderate quenching of the luminescence. Furthermore, the band gap of DAAzF is significantly influenced by pressure. As the color undergoes a transition from yellow to red, and becomes darker as the pressure increases, the absorption edge shifted towards red. At 3.4, 9, and 21 GPa, three conformational variations were identified in conjunction with electronic structural alterations.

Changes in molecular conformation and electronic structure of DNA under 12C ions based on first-principles calculations

Fundamental studies on the interaction between ionizing radiation and deoxyribonucleic acid (DNA) can contribute to understanding the biological effects of radiation protection and radiotherapy. The transitional process from ionized and excited DNA to DNA lesions, such as strand breaks and base lesions, remains uncertain. In this study, we focused in particular on the direct effects of radiation on DNA and calculated the number of ionizations induced within 10 base pairs of DNA using the Particle and Heavy Ion Transport code System, a general-purpose Monte Carlo code for radiation transport. The electronic structure of the ionized DNA is subsequently calculated using the first-principles calculation software OpenMX. Through these calculations, we successfully identified the redox site of DNA and quantitatively evaluated the amount of molecular bond cleavage. The scientific findings of this study will elucidate the cleavage mechanism of DNA in the high-density radiation field realized by ion beam irradiation by determining the redox sites.

Rapid measurement of hemoglobin-oxygen dissociation by leveraging Bohr effect and Soret band bathochromic shift.

Oxygen (O2) binds to hemoglobin (Hb) in the lungs and is then released (dissociated) in the tissues. The Bohr effect is a physiological mechanism that governs the affinity of Hb for O2 based on pH, where a lower pH results in a lower Hb-O2 affinity and higher Hb-O2 dissociation. Hb-O2 affinity and dissociation are crucial for maintaining aerobic metabolism in cells and tissues. Despite its vital role in human physiology, Hb-O2 dissociation measurement is underutilized in basic research and in clinical laboratories, primarily due to the technical complexity and limited throughput of existing methods. We present a rapid Hb-O2 dissociation measurement approach by leveraging the Bohr effect and detecting the optical shift in the Soret band that corresponds to the light absorption by the heme group in Hb. This new method reduces Hb-O2 dissociation measurement time from hours to minutes. We show that Hb deoxygenation can be accelerated chemically at the optimal pH of 6.9. We show that time and pH-controlled deoxygenation of Hb results in rapid and distinct conformational changes in its tertiary structure. These molecular conformational changes are manifested as significant, detectable shifts in Hb's optical absorption spectrum, particularly in the characteristic Soret band (414 nm). We extensively validated the method by testing human blood samples containing normal Hb and Hb variants. We show that rapid Hb-O2 dissociation can be used to screen for and detect Hb-O2 affinity disorders and to evaluate the function and efficacy of Hb-modifying therapies. The ubiquity of optical absorption spectrophotometers positions this approach as an accessible, rapid, and accurate Hb-O2 dissociation measurement method for basic research and clinical use. We anticipate this method's broad adoption will democratize the diagnosis and prognosis of Hb disorders, such as sickle cell disease. Further, this method has the potential to transform the research and development of new targeted and genome-editing-based therapies that aim to modify or improve Hb-O2 affinity.

Molecular recognition of ITIM/ITSM domains with SHP2 and their allosteric effect.

Src homology 2-domain-containing tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase that is widely expressed in a variety of cells and regulates the immune response of T cells through the PD-1 pathway. However, the activation mechanism and allosteric effects of SHP2 remain unclear, hindering the development of small molecule inhibitors. For the first time, in this study, the complex structure formed by the intact PD-1 tail and SHP2 was modeled. The molecular recognition and conformational changes of inactive/active SHP2 versus ITIM/ITSM were compared based on prolonged MD simulations. The relative flexibility of the two SH2 domains during MD simulations contributes to the recruitment of ITIM/ITSM and supports the subsequent conformational change of SHP2. The binding free energy calculation shows that inactive SHP2 has a higher affinity for ITIM/ITSM than active SHP2, mainly because the former's N-SH2 refers to the α-state. In addition, a significant decrease in the contribution to the binding energy of certain residues (e.g., R32, S34, K35, T42, and K55) of conformationally transformed SHP2 contributes to the above result. These detailed changes during conformational transition will provide theoretical guidance for the molecular design of subsequent novel anticancer drugs.

The Geometry of Nanoparticle-on-Mirror Plasmonic Nanocavities Impacts Surface-Enhanced Raman Scattering Backgrounds.

Surface-enhanced Raman scattering (SERS) has garnered substantial attention due to its ability to achieve single-molecule sensitivity by utilizing metallic nanostructures to amplify the exceedingly weak Raman scattering process. However, the introduction of metal nanostructures can induce a background continuum which can reduce the ultimate sensitivity of SERS in ways that are not yet well understood. Here, we investigate the impact of laser irradiation on both Raman scattering and backgrounds from self-assembled monolayers within nanoparticle-on-mirror plasmonic nanocavities with variable geometry. We find that laser irradiation can reduce the height of the monolayer by inducing an irreversible change in molecular conformation. The resulting increased plasmon confinement in the nanocavities not only enhances the SERS signal, but also provides momentum conservation in the inelastic light scattering of electrons, contributing to the enhancement of the background continuum. The plasmon confinement can be modified by changing the size and the geometry of nanoparticles, resulting in a nanoparticle geometry-dependent background continuum in SERS. Our work provides new routes for further modifying the geometry of plasmonic nanostructures to improve SERS sensitivity.

Theoretical perspective for hydrostatic pressure responsive mechanism of room temperature phosphorescence molecules

Stimulus-responsive organic room temperature phosphorescence (RTP) materials are a class of materials that show emission property changes when subjected to diverse environmental stimuli. The change of molecular stacking modes and intermolecular interactions can result in mechanical stimulus-induced emission switching behaviour. The underlying mechanism of mechanoresponsive luminescent material is still unclear. Herein, based on density functional theory and time-dependent density functional theory calculations, the photophysical properties with response to hydrostatic pressure of RTP molecules in crystal are theoretically studied. Excited state dynamic processes are investigated by using quantum mechanics and molecular mechanics method coupled with thermal vibration correlation function method. Results show that the increase of pressure can blue-shift the RTP emissions which is mainly caused by the change of molecular conformation and the increase of bending vibration frequency. Under 2 Gpa, large spin–orbit coupling effect is determined, remarkable radiative and non-radiative decay processes are achieved. At 0.6 Gpa, a small non-radiative decay rate from T 1 to S 0 is obtained, high efficiency and long lifetime (more than 10 times the other pressures) are realised. Through further analysing the staking modes, reorganisation energies and SOC constants, relationships between molecular structures and RTP properties are determined, hydrostatic pressure responsive mechanism is revealed.

Ultrasensitive, dynamic, and online monitoring photonic sensors for protein conformation

The monitoring of molecular dynamic transition and protein conformation changes is important for some neurodegenerative diseases (NDs) and has attracted much attention due to its ability to reveal the pathological mechanism of several NDs. Here, a label-free optical detection method with an ultrahigh refractive index sensitivity (S) and dynamical S tuning range was developed to provide a novel technology roadmap for the online monitoring of protein conformation. The real-time conformation variation process was transduced into a visualization optical signal, allowing it to be monitored. The biosensor prototype was constructed by the cross-overlapping of two rows of square capillaries on a gold mirror to form two microcavities with different free spectral ranges (denoted as the sensing and reference cavities). The coupling of the resonance mode between the two microcavities induced the generation of the Vernier effect and the magnifying of S, presented in the form of a modulated envelope in the spectrum. S values ranged from −17,256 nm/RIU to 93,937 nm/RIU, indicating that the biosensor could not only realize large dynamic tuning ranges but also an ultrahigh S. The conformation changes of silk proteins from the random coil to the β–sheet were sensitively monitored by the output spectrum after it was stimulated with ethanol solution. This ultrasensitive biosensor (which is both label-free and optical) provides a novel and supplementary technique to monitor the structural and conformation changes process of proteins. The results reveal its significant potential for clinical diagnosis, healthcare, pharmaceutical screening, and food security.

Impact of pH and NaCl on the molecular conformation of myosin and myosin microgel and underlying mechanism: A comprehensive study using spectroscopy and molecular dynamics simulation

The conformation of myosin in its natural and denatured state can be changed by adjusting the pH and NaCl concentration. Raman spectroscopy, endogenous fluorescence, scanning electron microscopy, and molecular dynamics (MD) were used to observe the molecular conformational changes of tilapia myosin and myosin microgel (MM). When the NaCl concentration was 0.6 mol/L and the pH was 7.0, myosin and MM were in a fibrillated state, contained a high α-helix content, exhibited the highest intensity of endogenous fluorescence, and showed a loose conformation (Rgmyosin: 3.32 ± 0.06 nm, RgMM: 3.11 ± 0. 01 nm), and high solvent-accessibility surface area (SASA) (SASAmyosin: 406 ± 4 nm2; SASAMM: 378 ± 3 nm2) with high secondary structure stability. The pH and NaCl affected the SASA, hydrogen bonding number, and charge of myosin and MM, leading to secondary structure and conformational changes. Compared to NaCl, the pH exhibited a greater effect on the conformation of myosin and MM, and MM improved the stability of the protein. In conclusion, this study clarified the above mentioned conformational changes in proteins at the molecular level, which may facilitate the development of myosin in food processing.

Atomic high-spin cobalt(II) center for highly selective electrochemical CO reduction to CH3OH

In this work, via engineering the conformation of cobalt active center in cobalt phthalocyanine molecular catalyst, the catalytic efficiency of electrochemical carbon monoxide reduction to methanol can be dramatically tuned. Based on a collection of experimental investigations and density functional theory calculations, it reveals that the electron rearrangement of the Co 3d orbitals of cobalt phthalocyanine from the low-spin state (S = 1/2) to the high-spin state (S = 3/2), induced by molecular conformation change, is responsible for the greatly enhanced CO reduction reaction performance. Operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy measurements disclose accelerated hydrogenation of CORR intermediates, and kinetic isotope effect validates expedited proton-feeding rate over cobalt phthalocyanine with high-spin state. Further natural population analysis and density functional theory calculations demonstrate that the high spin Co2+ can enhance the electron backdonation via the dxz/dyz−2π* bond and weaken the C-O bonding in *CO, promoting hydrogenation of CORR intermediates.

Disorder-Enhanced Charge-Transfer-Mediated Room-Temperature Phosphorescence in Polymer Media.

Room-temperature phosphorescence (RTP) polymers have important applications for biological imaging, oxygen sensing, data encryption, and photodynamic therapy. Despite the many advantages polymeric materials offer such as great control over gas permeability and processing flexibility, disorder is traditionally considered as an intrinsic negative impact on the efficiency for embedded RTP luminophores, as various allowed thermal motions could quench the emitting states. However, we propose that such disorder-enabled freedoms of microscopic motions can be beneficial for charge-transfer-mediated RTP, which is facilitated by molecular conformational changes among different electronic transition states. Using the "classic" pyrene-aniline exciplex as an example, we demonstrate the mutual enhancement of red/near-infrared and green RTP emissions from the pyrene and aniline moieties, respectively, upon doping the aniline polymer with trace pyrene derivatives. In comparison, a pyrene-doped crystal formed with the same aniline structure exhibits only charge-transfer fluorescence with no red or green RTP observed, suggesting that order suppresses the RTP channels. The proposed polymerization strategy may be used as a unified method to generate multi-emissive polymeric RTP materials from a vast pool of known and unknown exciplexes and charge-transfer complexes.

Disorder‐Enhanced Charge‐Transfer‐Mediated Room‐Temperature Phosphorescence in Polymer Media

AbstractRoom‐temperature phosphorescence (RTP) polymers have important applications for biological imaging, oxygen sensing, data encryption, and photodynamic therapy. Despite the many advantages polymeric materials offer such as great control over gas permeability and processing flexibility, disorder is traditionally considered as an intrinsic negative impact on the efficiency for embedded RTP luminophores, as various allowed thermal motions could quench the emitting states. However, we propose that such disorder‐enabled freedoms of microscopic motions can be beneficial for charge‐transfer‐mediated RTP, which is facilitated by molecular conformational changes among different electronic transition states. Using the “classic” pyrene‐aniline exciplex as an example, we demonstrate the mutual enhancement of red/near‐infrared and green RTP emissions from the pyrene and aniline moieties, respectively, upon doping the aniline polymer with trace pyrene derivatives. In comparison, a pyrene‐doped crystal formed with the same aniline structure exhibits only charge‐transfer fluorescence with no red or green RTP observed, suggesting that order suppresses the RTP channels. The proposed polymerization strategy may be used as a unified method to generate multi‐emissive polymeric RTP materials from a vast pool of known and unknown exciplexes and charge‐transfer complexes.

Photo-Controlled Self-Assembly of Nanoparticles: A Promising Strategy for Development of Novel Structures.

Photo-controlled self-assembly of nanoparticles (NPs) is an advanced and promising approach to address a series of material issues from the molecular level to the nano/micro scale, owing to the fact that light stimulus is typically precise and rapid, and can provide contactless spatial and temporal control. The traditional photo-controlled assembly of NPs is based on photochemical processes through NPs modified by photo-responsive molecules, which are realized through the change in chemical structure under irradiation. Moreover, photoexcitation-induced assembly of NPs is another promising physical strategy, and such a strategy aims to employ molecular conformational change in the excited state (rather than the chemical structure) to drive molecular motion and assembly. The exploration and control of NP assembly through such a photo-controlled strategy can open a new paradigm for scientists to deal with "bottom-up" behaviors and develop unprecedented optoelectronic functional materials.