Molecular Conformational Changes Research Articles

Fluorescence of molecular composites that consist of nematic liquid crystal and merocyanins

Background: Considered merocyanine molecules have donor D and acceptor A moieties connected by polymer chain. The conjugated donor D and acceptor A parts of merocyanine molecules are planar in the ground state. The D-π-A molecular complexes can change their conformations in an excited state due to cis-trans-conformational transitions. The viscosity of the solvent affects conformational changes, photoluminescence (PL) decay and PL lifetime. Therefore the PL of merocyanine molecules strongly depends on medium in excited and ground states. A nematic liquid crystal was utilized as a solvent for merocyanine molecules since it is characterized by long range order, orientates merocyanine molecules along its axis and is sensitive to external electro-magnetic field. The molecules with conjugated donor D and acceptor A parts are promising for molecular electronics (instruments for recording and processing information), optoelectronics (laser technologies) and biological research (fluorescent probes like prominent thioflavin T), since their PL essentially depends on the nature of the environment. Objectives: The main objective of this paper is to investigate and explain impact of liquid crystal medium on considered molecules. Also influence of molecular conformational changes on their spectral properties is considered. Materials and Methods: Two types of merocyanine molecules M-1 and M-2 were investigated. The spectral properties of molecules in different organic solvents such as acetonitrile, toluene, glycerol, and in 4-pentyl-4′-cyanobiphenyl (5CB) liquid crystal were compared. Stationary and time-resolved emission spectra of molecular merocyanine solutions were used to investigate conformational changes of molecules. To determine a lifetime of molecular excited states, a technique of Time Correlated Single Photon Counting with picosecond resolution in time was used. Results: The results indicate that optical properties strongly depend on conformation of conjugated donor-π-acceptor compounds. A relaxation of dye molecules to the ground state is accompanied by conformational changes. The quantum yield and lifetime of PL increase in more viscous solvents. The liquid crystal made conformational changes of considered molecules in ground and excited states. Conclusions: Analysis of the results serves as a basis for constructing a theory that explains properties of D-π-A molecular compounds under optical excitation. The molecular pairs are formed by merocyanine and liquid crystal molecules. The liquid crystal molecule defines conformation of merocyanine molecule in a pair. Moreover, both types of merocyanine molecules in liquid crystal have the same conformation. This hypothesis explains similarities of optical properties of M-1 and M-2 molecules in liquid crystal.

A Magnetic Drug Delivery System with "OFF-ON" State via Specific Molecular Recognition and Conformational Changes for Precise Tumor Therapy.

To enhance the tumor-targeting and tumor cell-specific drug-release capacity of nano drug delivery systems, a magnetic resonance imaging-traceable, magnetic-targeted nanoplatform is developed, and the nanoplatform is prepared by capping mesoporous silica (MSN)-coated iron oxide nanoparticles (IONPs) with programmable DNA hairpin sensor "gates." In normal cells (HL-7702, human liver cells), the nanoplatform is able to entrap the loaded drugs, showing an "OFF" state; the nanoplatform is activated by endogenous miRNA-21 overexpressed in tumor cells (HepG2, human liver tumor cells), which serve as an exclusive key to unlock the nanoplatform through hybridization with programmable DNA hairpin, leading to a rapid drug release, showing an "ON" state. The nanoplatform exhibits high antitumor efficacy and low toxicity in in vitro and in vivo studies owing to its magnetic targeting and tumor cell-activated properties, paving the way for targeted and personalized tumor treatment and showing potential for clinical applications.

Local and Global Stretching of Polymer Chains during Startup of Extensional Flow.

The nonlinear rheological response to extensional flows in entangled polymers is related to the segmental chain stretching and to the chemical identity of the monomeric units. The latter has a strong effect on the drag coefficients, and therefore, quantification of molecular conformation changes in the subnanometer scale (at the monomer level) are crucial to fully understand nonlinear viscoelastic behavior in polymer melts. We report in situ time-resolved extensional rheo-small-angle neutron scattering (tEr-SANS) and wide-angle X-ray scattering (tEr-WAXS) during startup of uniaxial flow on a monodisperse polystyrene melt. Flow-induced segmental alignment was quantified with tEr-SANS, whereas local alignment of the backbone-backbone and phenyl-phenyl interactions were measured with tEr-WAXS. Linear relations between the three alignment factors and stress were observed at low stresses, which confirmed the validity of simple stress-SANS and stress-WAXS rules (SSR and SWR, respectively). Significant differences in SSR and SWR coefficients, as well as the stress values for failure of the two rules suggest very different correlations between global (at the segmental level) and local (at the monomer level) conformations with stress.

Effect of pulsed electric field on assembly structure of α-amylase and pectin electrostatic complexes

Pulsed electric field (PEF) could change the charge distribution of proteins and polysaccharides and affect their interactions and complexes aggregation, but those influences are not enough evaluated. Here, the effects of PEF on the complexes of α-amylase and pectin driven by electrostatic binding were studied. Changes in molecular conformation of α-amylase and assembly structure of α-amylase/pectin complexes were orderly assessed by fluorescence, FTIR, DSC, enzyme activities, particle size, ζ-potential, CLSM, and SEM. After PEF treatment (E~20 kV/cm, texp~1 ms, and 5 cycles), the intrinsic fluorescence of α-amylase was quenched, the content of β-sheet increased, enzyme activities lose almost 80%, and the denatured temperature increased. Ζeta-potential of α-amylase/pectin complexes did not change significantly, but the particle size rose gradually. The particle revolution of α-amylase/pectin complexes was recorded by Turbiscan, and the size growth model fit the Allometric function well. Finally, the complexes of α-amylase and pectin after PEF treatment tended to the branched, ring, or circles-like shape.

Effect of salt and temperature on molecular aggregation behavior of acrylamide polymer

AbstractThree kinds of acrylamide copolymers were synthesized in this paper, acrylamide (AM) homopolymer, acrylamide/acrylic acid (AA) copolymer and acrylamide/2-acrylamide-2-methylpropanesulfonic acid (AMPS) copolymer by free radical polymerization. The aggregation behaviours of these polymers in salts water solution were studied. The molecular chains of homopolymer were stretched in salt water solutions, since it did not undergo hydrolysis and there were no charges in the backbone and side chains. Therefore, the conformation of homopolymer was hard to be attacked by salt ions. However, the copolymers synthesized from these monomers had large number of anionic groups. These anions were easily attracted by cations from salt solutions forming ionic bonds, which led to changes in molecular conformation. The viscosity of copolymer decreased since the molecular chains were crimped. The viscosity of copolymer decreased distinctly according to the temperature of different salt solutions, as temperature had great impact on the viscosity of copolymer. The interaction mechanism of polymers exhibited great difference in salts solutions, comparing to temperature. High temperature reduced the entanglement between molecular chains, whereas salt ions neutralized the negative charges on the molecular chains causing curling of molecular chains.

Outer hair cell electromotility is low-pass filtered relative to the molecular conformational changes that produce nonlinear capacitance.

The outer hair cell (OHC) of the organ of Corti underlies a process that enhances hearing, termed cochlear amplification. The cell possesses a unique voltage-sensing protein, prestin, that changes conformation to cause cell length changes, a process termed electromotility (eM). The prestin voltage sensor generates a capacitance that is both voltage- and frequency-dependent, peaking at a characteristic membrane voltage (Vh), which can be greater than the linear capacitance of the OHC. Accordingly, the OHC membrane time constant depends upon resting potential and the frequency of AC stimulation. The confounding influence of this multifarious time constant on eM frequency response has never been addressed. After correcting for this influence on the whole-cell voltage clamp time constant, we find that both guinea pig and mouse OHC eM is low pass, substantially attenuating in magnitude within the frequency bandwidth of human speech. The frequency response is slowest at Vh, with a cut-off, approximated by single Lorentzian fits within that bandwidth, near 1.5 kHz for the guinea pig OHC and near 4.3 kHz for the mouse OHC, each increasing in a U-shaped manner as holding voltage deviates from Vh Nonlinear capacitance (NLC) measurements follow this pattern, with cut-offs about double that for eM. Macro-patch experiments on OHC lateral membranes, where voltage delivery has high fidelity, confirms low pass roll-off for NLC. The U-shaped voltage dependence of the eM roll-off frequency is consistent with prestin's voltage-dependent transition rates. Modeling indicates that the disparity in frequency cut-offs between eM and NLC may be attributed to viscoelastic coupling between prestin's molecular conformations and nanoscale movements of the cell, possibly via the cytoskeleton, indicating that eM is limited by the OHC's internal environment, as well as the external environment. Our data suggest that the influence of OHC eM on cochlear amplification at higher frequencies needs reassessment.

Reversible Mechanical Regulation and Splicing Ability of Alginate-Based Gel Based on Photo-Responsiveness of Molecular-Level Conformation.

In this study, benefiting from the sensitive molecular conformation transversion in azobenzene, a new strategy for fabricating alginate gels with the abilities of splicing and photo-responsive mechanical adjustment is reported. Firstly, a 4,4’-azobis(benzoylhydrazide) (Azo-hydrazide) linker was used to crosslink alginate physically via the electrostatic interaction between hydrazide groups and carboxyl groups. It was then shaped and transferred in situ to a chemically crosslinked gel via 450 nm light irradiation. Under the irradiation, the molecular conformation change of azobenzene in the linker was able to form covalent bonds at the crosslinking points of the gels. Furthermore, the reversible conformation transformation of azobenzene was able to induce the increase and decrease of the storage modulus under irradiation with 365 nm light and 450 nm light, respectively, while also providing gel-like mechanical properties, depending upon the irradiation time and given wavelength. Meanwhile, the results also indicated that active groups could contribute to the splicing ability of the gel and construct a hollow cavity structure. It is believed that this work could provide a versatile strategy for preparing photo-responsive gels with reversibly tunable mechanical properties.

A Diastereodynamic Probe Transducing Molecular Length into Chiroptical Readout.

Nature takes advantage of molecular conformational changes to express functions such as signaling across cellular membranes or allosteric protein activation. At the synthetic level, molecular recognition events have been used to induce conformational changes able to trigger functions such as catalysis or sensing. In this context, transduction of stereochemical information has been the leading strategy. In particular, stereodynamic elements have been extensively employed to amplify and/or transduce chiral information. In this article, we report a chiral supramolecular cage with two stereodynamic units, which invert their helicities according to the length of the molecular guest confined within the system. Interestingly, achiral information is transduced by the supramolecular system to different diastereomeric states that have opposite chiroptical absorptions. This is the first example in which it is possible to produce a continuous modulation of the chiroptical output of a system by varying a physical achiral molecular property (viz. molecular dimension). This phenomenon can be exploited for the establishment of novel methods to program conformational control, for the development of innovative sensors and/or for transduction of molecular properties into chiroptical information.

Research progress in the characterization of protein adsorption on biomaterial surface

The characterization methods in the field of protein adsorption on biological materials in recent years were reviewed from the aspects of protein adsorption amount, adsorption layer thickness, molecular conformational change after protein adsorption, molecular morphology after protein adsorption, and protein molecule adsorption process simulation. These methods include biochemical analysis, surface plasmon resonance (SPR), dissipative quartz crystal microbalance (QCM-D), ellipsometry (ELM), optical interference reflection (RIFS), attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), circular dichroism (CD), atomic force microscopy (AFM) and computer molecular simulation techniques. In this paper, the basic principles, the advantages and disadvantages of the above characterization methods and related researches were reviewed. This paper provides a comprehensive and reliable basis for the selection of protein experimental characterization methods in protein adsorption, biomaterial design and other research, and provides new ideas for research in the field of protein. Key words: Protein; Adsorption; Biomaterial; Characterization

Conformational manipulation of scale-up prepared single-chain polymeric nanogels for multiscale regulation of cells

Folded single chain polymeric nano-objects are the molecular level soft material with ultra-small size. Here, we report an easy and scalable method for preparing single-chain nanogels (SCNGs) with improved efficiency. We further investigate the impact of the dynamic molecular conformational change of SCNGs on cellular interactions from molecular to bulk scale. First, the supramolecular unfoldable SCNGs efficiently deliver siRNAs into stem cells as a molecular drug carrier in a conformation-dependent manner. Furthermore, the conformation changes of SCNGs enable dynamic and precise manipulation of ligand tether structure on 2D biomaterial interfaces to regulate the ligand–receptor ligation and mechanosensing of cells. Lastly, the dynamic SCNGs as the building blocks provide effective energy dissipation to bulk biomaterials such as hydrogels, thereby protecting the encapsulated stem cells from deleterious mechanical shocks in 3D matrix. Such a bottom-up molecular tailoring strategy will inspire further applications of single-chain nano-objects in the biomedical area.

Multi-spectroscopic measurements, molecular modeling and density functional theory calculations for interactions of 2,7-dibromocarbazole and 3,6-dibromocarbazole with serum albumin

2,7-Dibromocarbazole (2,7-DBCB) and 3,6-dibromocarbazole (3,6-DBCB) are emerging environmental pollutants, being potentially high risks to human health. In this study, interactions of the two compounds with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated by molecular modeling, density functional theory calculations (DFT) and multispectral techniques. The static quenching interaction deduced in the fluorescence quenching experiment is confirmed by the time-resolved analyses. The interactions of the two compounds with HSA/BSA induce molecular microenvironment and conformation changes, as assessed by synchronous and 3D fluorescence spectra, together with a destruction of polypeptide carbonyl hydrogen bond network by circular dichroism and Fourier transform infrared analyses. The thermodynamic analysis indicated that the spontaneous interaction was hydrogen bonding and hydrophobic forces. The binding constant Ka at 298 K was 3.54 × 105 M−1 in HSA-2,7-DBCB, 6.63 × 105 M−1 in HSA-3,6-DBCB, 1.32 × 105 M−1 in BSA-2,7-DBCB and 2.17 × 105 M−1 in BSA-3,6-DBCB. These results indicates that 3,6-DBCB binds HSA/BSA more strongly than 2,7-DBCB, which was estimated with DFT calculations. Site marker competition experiments coupled with molecular modeling studies confirmed that both compounds bind HSA/BSA at site I (subdomain IIA). The results suggest that interactions between 2,7-DBCB and 3,6-DBCB with HSA and BSA may affect the normal physiological activities in human and animals.

Differential cellular contractility as a mechanism for stiffness sensing

The ability of cells to sense and respond to the mechanical properties of their environments is fundamental to a range of cellular behaviours, with substrate stiffness increasingly being found to be a key signalling factor. Although active contractility of the cytoskeleton is clearly necessary for stiffness sensing in cells, the physical mechanisms connecting contractility with mechanosensing and molecular conformational change are not well understood. Here we present a contractility-driven mechanism for linking changes in substrate stiffness with internal conformational changes. Cellular contractility is often assumed to imply an associated compressive strain. We show, however, that where the contractility is non-uniform, localized areas of internal stretch can be generated as stiffer substrates are encountered. This suggests a physical mechanism for the stretch-activation of mechanotransductive molecules on stiffer substrates. Importantly, the areas of internal stretch occur deep within the cell and not near the cellular perimeter, which region is more traditionally associated with stiffness sensing through e.g. focal adhesions. This supports recent experimental results on whole-cell mechanically-driven mechanotransduction. Considering cellular shape we show that aspect ratio acts as an additional control parameter, so that the onset of positive strain moves to higher stiffness values in elliptical cells.

Remarkable photo-induced crystal transition accompanying with room temperature phosphorescence change

Limited works are reported about photochromism type room temperature phosphorescence luminogens (RTPs) owing to notorious quenching effect and lacking of reliable guidance. Here we have demonstrated an organic crystal (4-iodophenyl terpyridine) exhibiting photochromism and slowly spontaneous heat recovery. The photochromic crystal can be formed within a few minutes, and it once formed is stable for hours. Fortunately, the single crystals before and after photochromism are all analyzable and clearly indicate molecular conformation and packing structure change. It is deduced that photoactivation has induced single bond internal rotations and intermolecular slipping to form a metastable crystal with more planar molecular conformation and looser stacking. The different molecular conformation and packing structure have changed intermolecular interaction nature, which should be responsible for their different RTP properties.

Infrared Vibrational Spectroscopy of Functionalized Atomic Force Microscope Probes using Resonantly Enhanced Infrared Photoexpansion Nanospectroscopy

AbstractReported is the measurement of infrared absorption spectra of 4‐nitrothiophenol and hydroxyl‐terminated hexa(ethylene glycol) molecules at apices of functionalized atomic force microscope (AFM) probes using resonantly enhanced infrared photoexpansion nanospectroscopy, also known as resonantly enhanced AFM‐IR technique. The experiment demonstrates the applicability of the AFM‐IR technique to perform spectroscopy of only a few tens of molecules on AFM tip apices and demonstrates the potential of the AFM‐IR technique to perform vibrational spectroscopic studies of chemical reactions and molecular conformational changes on the apices of functionalized AFM tips.

Solid‐State Photochromism by Molecular Assembly of Bis‐o‐carboranyl Siloles

A new type of solid-state photochromism was observed in an AB2 -type molecular assembly comprising a central silole and two peripheral o-carborane units, and in this assembly, depending on the assembling positions of those units at the adjoining benzene ring, two different regioisomers were formed: Si-m-Cb and Si-p-Cb. Each isomer showed different solid-state photochromism depending on its solid-state molecular conformation and was either in the crystalline or amorphous state. The crystals of each meta- or para-isomer, CSi-m-Cb or CSi-p-Cb , showed yellow or blue emission, and mechanically grinding those crystals into amorphous powders of ASi-m-Cb and ASi-p-Cb , switched their emissions to blue and yellow, respectively. Photophysical studies revealed that the electronic interaction between silole and o-carborane units determined the emission color. The crystal and DFT-optimized structures each account for the crystalline and amorphous structures, respectively, and are correlated well with the electronic interactions in the molecular assembly in the solid state, thus enabling the prediction of the solid-state molecular conformational change.

Impact of molecular conformation on transport and transport-related properties at the nanoscale

Among the various factors influencing the charge transport through molecular electronic devices, changes in molecular conformation are of interest also because they do not have counterpart in traditional electronics. Out of the multitude of issues that are relevant from this perspective, in the present work we discuss aspects relevant for molecules forming self-assembled monolayers (SAMs) adsorbed on metallic electrodes in the limiting cases of low coverage and high coverage, respectively. The molecules to be examined, which are very common work-horses of molecular electronics, are in both cases easily deformable (“floppy”) species. In the former case, the specific molecule to be considered is azurin, an archetype of soluble redox proteins containing metal ions. Biphenylene monothiol and 4-(4-pyridinyl)benzenethiol, the specific molecules chosen for the analysis of the second case, are representative for the class of molecules consisting of two aromatic (benzene or benzene derivative) rings that can easily rotate relative to each other. The possibility to quantitatively describe the charge transport as a one-step coherent tunneling mechanism is the main aspect that will be emphasized in the former case. This is important because the charge transport in systems where molecular conformation substantially changes is commonly assumed to be a two-step hopping process and described within flavors of Marcus type formulas, which turned out to be invalidated by the azurin transport data examined. For high coverage situations, we present new results providing further support to our recent finding on the possibility to strongly enhance the twisting with respect to the situation of isolated molecules. Furthermore, we demonstrate that this twisting enhancement is not caused by the charge transfer at the metal-molecule interface. Rather, it represents an unusual effect of spatial confinement; although driven by the substrate metal, it can be theoretically modeled within a metal-free approach.

Strain-Dependent Structural Changes in Major and Minor Ampullate Spider Silk Revealed by Two-Photon Excitation Polarization.

Spider silk's mechanical properties make it an interesting material for many industrial applications. The structure and nanoscopic organization of its proteins are the basis of these qualities. In this study, the emission maxima of the autofluorescence from the protein core of major and minor ampullate silk fibers from the orb-web-weaving spider Nephila madagascariensis are determined and found to be 534 ± 11 and 547 ± 19 nm, respectively. Molecular conformational changes during applied strain are observed in both fiber types using two-photon excitation polarization measurements. Our findings showed that within the fibers the autofluorescent dipoles are separated into two distinct populations, one randomly orientated (amorphous regions) and one with aligned dipoles as found in crystalline structures. The crystalline-amorphous ratio was determined, and it was found that the crystalline dipoles made up around 30 and 20% of the autofluorescent dipoles in major and minor ampullate silk fibers, respectively. Using two-photon polarization measurements, it is possible to directly observe that the major and minor ampullate silk fibers structurally adapt to the applied stress, as well as discern different molecular conformational changes between major and minor ampullates. It was seen that the crystalline-amorphous ratio increased, with up to 9% for major fibers and 6% for minor fibers, as strain was applied, suggesting a conformational adaptation of the fiber, interpreted as noncrystalline 310-helices transforming into crystalline β-sheets.

OPEP6: A New Constant-pH Molecular Dynamics Simulation Scheme with OPEP Coarse-Grained Force Field.

The great importance of pH for molecular processes has motivated the continuous development of numerical methods to improve the physical description of molecular mechanisms in computer simulations. Although rigid titration models are able to provide several pieces of useful information, the coupling between the molecular conformational changes and the acid-base equilibrium is necessary to more completely model the pH effects in biomolecules. Previously reported convergence issues with atomistic simulations indicated that a promising approach would require coarse-grained models. By means of the coupling between the successful OPEP force field for proteins with the fast proton titration scheme, we proposed a new protocol for constant-pH molecular dynamics simulations that takes advantage of both coarse-grained approaches to circumvent sampling difficulties faced by other numerical schemes and also to be able to properly describe electrostatic and structural properties at lower CPU costs. Here, we introduce this new protocol that defines now OPEP6 and its p Ka's benchmark for a set of representative proteins (HP36, BBL, HEWL, NTL9, and a protein G variant). In comparison with experimental measurements, our calculated p Ka values have the average, maximum absolute, and root-mean-square deviations of [0.3-1.1], [0.6-2.5], and [0.4-1.3] pH units, respectively, for these five studied proteins. These numbers are within the ones commonly observed when similar comparisons are done among different theoretical models and are slightly better than the accuracy obtained by a rigid model using the same titration engine. For BBL, the predicted p Ka are closer to experimental results than other analyzed theoretical data. Structural properties were tested for insulin where separation distances between the groups were compared and found in agreement with experimental crystallographic data obtained at different pH conditions. These indicate the ability of the new OPEP to properly describe the system physics and open up more possibilities to study pH-mediated biological processes.

Uniaxial compression behavior and spectroscopic properties of energetic 1,1-diamino-2,2-dinitroethylene (FOX-7) crystals from density functional theory calculations

Using dispersion-corrected density functional theory (DFT), we investigate the effect of uniaxial compression on 1, 1-diamino-2, 2-dinitroethene (FOX-7) crystal. Principal and shear stresses along the [100], [010], and [001] orientations exhibit considerable anisotropic compressibility. Raman spectra are complemented by DFT calculations in vibrational modes. Several abnormal pressure-induced changes in selected Raman modes are observed along the [100] orientation. Combined Raman peak shifts with inter/intra-molecular hydrogen bonds and N−H/N−O covalent bonds, the results demonstrate that the spectroscopic variation are associated with the rearrangement of hydrogen-bonded networks of FOX-7 crystal. These findings imply a possible phase transformation or some minor changes in molecular conformation in the pressure regions under uniaxial compression.

Pressure induced phase transformations in diisopropylammonium bromide

Effect of high pressure on ferroelectric diisopropylammonium bromide (DIPAB) is investigated using Raman spectroscopy and angle-dispersive x-ray diffraction (XRD) measurements using a diamond anvil cell up to ∼10 GPa. Raman spectroscopic studies indicate that the monoclinic (m-II) ferroelectric phase of DIPAB is unstable under slight compression, leading to changes in molecular conformation. We have observed new peaks appearing in the lattice mode region and CH3 stretching region giving indication of conformational change. XRD investigations reveal that the m-II phase (space group P21) is partially transformed into a centrosymmetric, non-polar triclinic (P-1) structure at 0.7 GPa. Ferroelectricity is expected to weaken under compression above 0.7 GPa and ferroelectricity may disappear at a very high pressure when the m-II phase fully converted into triclinic P-1 phase. On releasing the pressure the ambient structure is fully recovered. The role of hydrogen bonds in the phase transformation is also discussed.