Binding abilities of a chiral calixresorcinarene: a polarimetric investigation on a complex case of study.
ABSTRACT: Polarimetry was used to investigate the binding abilities of a chiral calixresorcinarene derivative, bearing L-proline subunits, towards a set of suitably selected organic guests. The simultaneous formation of 1:1 and 2:1 host-guest inclusion complexes was observed in several cases, depending on both the charge status of the host and the structure of the guest. Thus, the use of the polarimetric method was thoroughly revisited, in order to keep into account the occurrence of multiple equilibria. Our data indicate that the stability of the host-guest complexes is affected by an interplay between Coulomb interactions, ?-? interactions, desolvation effects and entropy-unfavorable conformational dynamic restraints. Polarimetry is confirmed as a very useful and versatile tool for the investigation of supramolecular interactions with chiral hosts, even in complex systems involving multiple equilibria.
Project description:Purpose:To use machine learning in those with brain amyloid to predict thioflavin fluorescence (indicative of amyloid) of retinal deposits from their interactions with polarized light. Methods:We imaged 933 retinal deposits in 28 subjects with post mortem evidence of brain amyloid using thioflavin fluorescence and polarization sensitive microscopy. Means and standard deviations of 14 polarimetric properties were input to machine learning algorithms. Two oversampling strategies were applied to overcome data imbalance. Three machine learning algorithms: linear discriminant analysis, supporting vector machine, and random forest (RF) were trained to predict thioflavin positive deposits. For each method; accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were computed. Results:For the polarimetric positive deposits, using 1 oversampling method, RF had the highest area under the receiver operating characteristic curve (0.986), which was not different from that with the second oversampling method. RF had 95% accuracy, 94% sensitivity, and 97% specificity. After including deposits with no polarimetric signals, polarimetry correctly predicted 93% of thioflavin positive deposits. Linear retardance and linear anisotropy were the dominant polarimetric properties in RF with 1 oversampling method, and no polarimetric properties were dominant in the second method. Conclusions:Thioflavin positivity of retinal amyloid deposits can be predicted from their images in polarized light. Polarimetry is a promising dye-free method of detecting amyloid deposits in ex vivo retinal tissue. Further testing is required for translation to live eye imaging. Translational Relevance:This dye-free method distinguishes retinal amyloid deposits, a promising biomarker of Alzheimer's disease, in human retinas imaged with polarimetry.
Project description:Single crystal X-ray structures of halogen-bonded assemblies formed between host <i>N</i>-hexylammonium resorcinarene bromide (<b>1</b>) or <i>N</i>-cyclohexylammonium resorcinarene chloride (<b>2</b>), and 1,4-diiodooctafluorobutane and accompanying small solvent guests (methanol, acetonitrile and water) are presented. The guests' inclusion affects the geometry of the cavity of the receptors <b>1</b> and <b>2</b>, while the divalent halogen bond donor 1,4-diiodooctafluorobutane determines the overall nature of the halogen bond assembly. The crystal lattice of <b>1</b> contains two structurally different dimeric assemblies A and B, formally resulting in the mixture of a capsular dimer and a dimeric pseudo-capsule. <sup>1</sup>H and <sup>19</sup>F NMR analyses supports the existence of these halogen-bonded complexes and enhanced guest inclusion in solution.
Project description:Amyloid-? peptides (A?) fibrillation is the hallmark of Alzheimer's disease (AD). However, it has been challenging to discover potent agents in order to inhibit A? fibrillation. Herein, we demonstrated the effect of resorcinarene on inhibiting A? fibrillation in vitro via experimental and computational methods. A? were incubated with different concentrations of resorcinarene so as to monitor the kinetics by using thioflavin T binding assay. The results, which were further confirmed by far-UV CD spectroscopy and atomic force microscopy, strongly indicated that the higher concentration of resorcinarene, the more effective the inhibition of A? fibrillation. A cytotoxicity study showed that when sea urchin embryos were exposed to the resorcinarene, the majority survived due to the resorcinarene low toxicity. In addition, when the resorcinarene was added, the formation of toxic A? 42 species was delayed. Computational studies of A? fibrillation, including docking simulations and MD simulations, illustrated that the interaction between inhibitor resorcinarene and A? is driven by the non-polar interactions. These studies display a novel strategy for the exploration of promising antiamyloiddogenic agents for AD treatments.
Project description:The manipulation and characterization of light polarization states are essential for many applications in quantum communication and computing, spectroscopy, bioinspired navigation, and imaging. Chiral metamaterials and metasurfaces facilitate ultracompact devices for circularly polarized light generation, manipulation, and detection. Herein, we report bioinspired chiral metasurfaces with both strong chiral optical effects and low insertion loss. We experimentally demonstrated submicron-thick circularly polarized light filters with peak extinction ratios up to 35 and maximum transmission efficiencies close to 80% at near-infrared wavelengths (the best operational wavelengths can be engineered in the range of 1.3-1.6?µm). We also monolithically integrated the microscale circular polarization filters with linear polarization filters to perform full-Stokes polarimetric measurements of light with arbitrary polarization states. With the advantages of easy on-chip integration, ultracompact footprints, scalability, and broad wavelength coverage, our designs hold great promise for facilitating chip-integrated polarimeters and polarimetric imaging systems for quantum-based optical computing and information processing, circular dichroism spectroscopy, biomedical diagnosis, and remote sensing applications.
Project description:Optical polarimetry for monitoring glucose concentration in the aqueous humor of the eye as a potential noninvasive means of assessing blood glucose has promise, but the realization of such an approach has been limited by noise from time-varying corneal birefringence due to motion artifact. Modeling the corneal birefringence of the eye is critically important toward understanding the overall effect of this noise source compared to other changes in the signal, and can aid in design of the polarimetric system. To this end, an eye model is introduced in this work that includes spatially varying birefringence properties of the cornea. The degree of birefringence and the fast axis orientation is calculated as a function of beam position on the anterior chamber. It is shown that the minimum change in polarization vector orientation occurs for beam position near the midpoint between the corneal apex and limbus. In addition, the relative wavelength independence of motion artifact is shown in the same region. The direct consequence of these findings are that a multiwavelength polarimetric system can potentially be utilized to eliminate the effect of time-varying corneal birefringence, and that eye coupling is optimal at the midpoint between the apex and limbus.
Project description:Spatially Targeted Mass Spectrometry (MS) analysis using survey scans with an imaging modality often requires consecutive tissue slices, because of the tissue damage during survey scan or due to incompatible sample preparation requirements between the survey modality and MS. We report two spatially targeted MS analysis workflows based on polarized light imaging guidance that use the same tissue sample for survey and targeted analysis. The first workflow is applicable for thin-slice analysis, and uses transmission-polarimetry-guided Desorption ElectroSpray Ionization Mass Spectrometry (DESI-MS), and confirmatory H&E histopathology analysis on the same slice; this is validated using quantitative digital pathology methods. The second workflow explores a polarimetry-guided MS platform for thick tissue assessment by developing reflection-mode polarimetric imaging coupled with a hand-held Picosecond InfraRed Laser (PIRL) MS ablation probe that requires minimal tissue removal to produce detectable signal. Tissue differentiation within 5-10?s of sampling with the hand-held probe is shown using multivariate statistical methods of the MS profiles. Both workflows were tasked with differentiating necrotic cancer sites from viable cancers using a breast tumour model, and their performance was evaluated. The use of the same tissue surface addresses mismatches in guidance due to intrinsic changes in tissue morphology over consecutive sections.
Project description:Chiral molecular recognition is important to biology, separation, and asymmetric catalysis. Because there is no direct correlation between the chiralities of the host and the guest, it is difficult to design a molecular receptor for a chiral guest in a rational manner. By cross-linking surfactant micelles containing chiral template molecules, we obtained chiral nanoparticle receptors for a number of 4-hydroxyproline derivatives. Molecular imprinting allowed us to transfer the chiral information directly from the guest to host, making the molecular recognition between the two highly predictable. Hydrophobic interactions between the host and the guest contributed strongly to the enantio- and diastereoselective differentiation of these compounds in water, whereas ion-pair interactions, which happened near the surface of the micelle, were less discriminating. The chiral recognition could be modulated by tuning the size and shape of the binding pockets.
Project description:Simultaneous and efficient ultrafast recording of multiple photon tags contributes to high-dimensional optical imaging and characterization in numerous fields. Existing high-dimensional optical imaging techniques that record space and polarization cannot detect the photon's time of arrival owing to the limited speeds of the state-of-the-art electronic sensors. Here, we overcome this long-standing limitation by implementing stereo-polarimetric compressed ultrafast photography (SP-CUP) to record light-speed high-dimensional events in a single exposure. Synergizing compressed sensing and streak imaging with stereoscopy and polarimetry, SP-CUP enables video-recording of five photon tags (x, y, z: space; t: time of arrival; and ?: angle of linear polarization) at 100 billion frames per second with a picosecond temporal resolution. We applied SP-CUP to the spatiotemporal characterization of linear polarization dynamics in early-stage plasma emission from laser-induced breakdown. This system also allowed three-dimensional ultrafast imaging of the linear polarization properties of a single ultrashort laser pulse propagating in a scattering medium.
Project description:This paper describes a new class of ultrafast dynamic spectro-polarimetry based on a specially designed one-piece polarizing interferometer. It provides spectral polarimetric parameters of an anisotropic object in milliseconds with high precision. The proposed ultrafast spectro-polarimetry has no moving parts and it is highly robust to external noises. The one-piece polarizing interferometric scheme enables the world fastest and simplest solution in spectroscopic polarimetry. The distinct simple concept on one-piece polarizing interferometer can extract spectroscopic polarimetric parameters ?(k) and ?(k) precisely with a speed of over 200?Hz over the entire visible wavelength range with a spectral resolution of less than 1?nm. The proposed novel one-piece scheme will have a significant potential of a paradigm shift from lab to fab in polarization metrology.
Project description:The C-ethyl-2-methylresorcinarene (1) forms 1:1 in-cavity complexes with aromatic N,N'-dioxides, only if each of the aromatic rings has an N-O group. The structurally different C-shaped 2,2'-bipyridine N,N'-dioxide (2,2'-BiPyNO) and the linear rod-shaped 4,4'-bipyridine N,N'-dioxide (4,4'-BiPyNO) both form 1:1 in-cavity complexes with the host resorcinarene in C4v crown and C2v conformations, respectively. In the solid state, the host-guest interactions between the 1,3-bis(4-pyridyl)propane N,N'-dioxide (BiPyPNO) and the host 1 stabilize the unfavorable anti-gauche conformation. Contrary to the N,N'-dioxide guests, the mono-N-oxide guest, 4-phenylpyridine N-oxide (4PhPyNO), does not form an in-cavity complex in the solid state. The host-guest complexation and the relative guest affinities were studied through 1H?NMR competition experiments in methanol. Single-crystal X-ray crystallography of the 1:1 complexes supports the proposed solution-state structures, also revealing strong hydrogen bonds between the host and the guests, not observed in solution owing to hydrogen/deuterium (H/D) exchange processes in methanol.