Bioinspired Design of an Uncharged Ambipolar Helical Scaffold To Achieve Efficient Solid-State Proton Conduction.

This work demonstrates highly efficient solid-state proton conduction in helical organic scaffolds inspired by the biomolecule gramicidin A. The scaffold, 1, derived from a pyridine-2,6-dicarboxamide (PDC) residue adopts a helical conformation that is stabilized by a network of strong bifurcated intramolecular H-bonds between the polar residues that align the inner (concave) face of the molecule, while the aromatic units in 1 are oriented outwards. As a result, the helix attains an ambipolar nature just like gramicidin A. Two different solid forms of 1 could be isolated: a yellow solid from high-polarity solvents and an orange solid from low-polarity solvents. Single-crystal X-ray diffraction (SCXRD) studies showed that in the former, molecules of 1 are stacked in a homochiral fashion, while in the latter heterochiral stacks of 1 were present. The yellow form exhibited an almost ∼300-fold higher conductivity (of up to 0.12 mS cm-1 at 95 °C and 95 % relative humidity) than the orange form as a result of closer intermolecular proximity and lower activation energy of 0.098 eV, thus indicating a Grotthus mechanism of proton transport. This study establishes the key role of bioinspired design and controlled stereo-organization of such discrete uncharged organic molecules in achieving efficient solid-state proton conduction.

Novel phenanthridine amide analogs as potential anti-leishmanial agents: In vitro and in silico insights.

In the current work, sixteen novel amide derivatives of phenanthridine were designed and synthesized using 9-fluorenone, 4-Methoxy benzyl amine, and alkyl/aryl acids. The characterization of the title compounds was performed using LCMS, elemental analysis, 1HNMR, 13CNMR and single crystal XRD pattern was also developed for compounds A8. All the final analogs were screened in vitro for anti-leishmanial activity against promastigote form of L. infantum strain. Among the tested analogs, four compounds (A-06, A-11, A-12, and A-15) exhibited significant anti-leishmanial activity with EC50 value ranges from 8.9 to 21.96 µM against amastigote forms of tested L. infantum strain with SI ranges of 1.0 to 4.3. From the activity results it was found that A-11 was the most active compound in both promastigote and amastigotes forms with EC50 values 8.53 and 8.90 µM respectively. In-silico ADME prediction studies depicted that the titled compounds obeyed Lipinski's rule of five as that of the approved marketed drugs. The predicted in-silico toxicity profile also confirmed that the tested compounds were non-toxic. Finally, molecular docking and molecular dynamics study was also performed for significantly active compound (A-11) in order to study it's putative binding pattern at the active site of the selected leishmanial trypanothione reductase target as well as to understand the stability pattern of target-ligand complex for 100 ns. Single crystal XRD of compound A-08 revealed that the compound crystallizes in monoclinic C2/c space group and showed interesting packing arrangements.

High Pressure In Situ Single-Crystal X-Ray Diffraction Reveals Turnstile Linker Rotation Upon Room-Temperature Stepped Uptake of Alkanes.

The rare availability of suitable single-crystal X-ray diffraction (SCXRD) structural data allows for the direct interpretation of the response of a framework to gas sorption and may lead to the development of improved functional porous materials. We report an in situ SCXRD structural investigation of a flexible MOF subjected to methane, ethane, propane, and butane gas pressures. Supporting theoretical investigations indicate weak host-guest interactions for the crystallographically modelled gaseous guests and, in addition, reveal that a turnstile mechanism facilitates the transport of alkanes through the seemingly nonporous system. Inflections present in the adsorption isotherms are furthermore rationalized as due to gate-opening, but without the expected creation of new accessible space.

Quest for an Optimal Methane Hydrate Formation in the Pores of Hydrolytically Stable Metal-Organic Frameworks.

Porous metal-organic frameworks (MOFs) capable of storing a relatively high amount of dry methane (CH4) in the adsorbed phase are largely explored; however, solid CH4 storage in confined pores of MOFs in the form of hydrates is yet to be discovered. Here we report a rational approach to form CH4 hydrates by taking advantage of the optimal pore confinement in relatively narrow cavities of hydrolytically stable MOFs. Unprecedentedly, we were able to isolate methane hydrate (MH) nanocrystals with an sI structure encapsulated inside MOF pores with an optimal cavity dimension. It was found that confined nanocrystals require cavities slightly larger than the unit cell crystal size of MHs (1.2 nm), as exemplified in the experimental case study performed on Cr-soc-MOF-1 vs smaller cavities of Y-shp-MOF-5. Under these conditions, the excess amount of methane stored in the pores of Cr-soc-MOF-1 in the form of MH was found to be ≈50% larger than the corresponding dry adsorbed amount at 10 MPa. More importantly, the pressure gradient driving the CH4 storage/delivery process could be drastically reduced compared to the conventional CH4-adsorbed phase storage on the dry Cr-soc-MOF-1 (≤3 MPa vs 10 MPa).

Of Twists and Curves: Electronics, Photophysics, and Upcoming Applications of Non-Planar Conjugated Organic Molecules.

Non-planar conjugated organic molecules (NPCOMs) contain π-conjugation across their length and also exhibit asymmetry in their conformation. In other words, certain molecular fragments in NPCOMs are either twisted or curved out of planarity. This conformational asymmetry in NPCOMs leads to non-uniform charge-distribution across the molecule, with important photophysical and electronic consequences such as altered thermodynamic stability, chemical reactivity, as well as materials properties. Majorly, NPCOMs can be classified as having either Fused or Rotatable architectures. NPCOMs have been the focus of significant scientific attention in the recent past due to their exciting photophysical behavior that includes intramolecular charge-transfer (ICT), thermally activated delayed fluorescence (TADF) and long-lived charge-separated states. In addition, they also have many useful materials characteristics such as biradical character, semi-conductivity, dynamic conformations, and mechanochromism. As a result, rational design of NPCOMs and mapping their structure-property correlations has become imperative. Researchers have executed conformational changes in NPCOMs through a variety of external stimuli such as pH, temperature, anions-cations, solvent, electric potential, and mechanical force in order to tailor their photophysical, optoelectronic and magnetic properties. Converging to these points, this review highlights the lucrative electronic features, photophysical traits and upcoming applications of NPCOMs by a selective survey of the recent scientific literature.

Discovery of 1,2,3-triazole based quinoxaline-1,4-di-N-oxide derivatives as potential anti-tubercular agents.

A series of thirty one novel 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-3-methylquinoxaline-1,4-dioxide (7a-l), 3-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6-chloro-2-methylquinoxaline-1,4-dioxide (8a-l) and 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6,7-dichloro-3-methylquinoxaline-1,4-dioxide (9a-g) analogues were synthesized, characterized using various analytical techniques and single crystal was developed for the compounds 8 g and 9f. Synthesized compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two clinical isolates Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 30.35 to 252.00 µM. Among the tested compounds, 8e, 8 l, 9c and 9d exhibited moderate activity (MIC = 47.6 - 52.0 µM) and 8a exhibited significant anti-tubercular activity (MIC = 30.35 µM). Furthermore, 8e, 8 l, and 9d were found to be less toxic against human embryonic kidney, HEK 293 cell lines. Finally, a docking study was also performed using MTB DNA Gyrase (PDB ID: 5BS8) for the significantly active compound 8a to know the exact binding pattern within the active site of the target enzyme.

Unprecedented Ultralow Detection Limit of Amines using a Thiadiazole-Functionalized Zr(IV)-Based Metal-Organic Framework.

A luminescent Zr(IV)-based metal-organic framework (MOF), with the underlying fcu topology, encompassing a π-conjugated organic ligand with a thiadiazole functionality, exhibits an unprecedented low detection limit of 66 nM for amines in aqueous solution. Markedly, this ultralow detection is driven by hydrogen-bonding interactions between the linker and the hosted amines. This observation is supported by density functional theory (DFT) calculations, which clearly corroborate the suppression of the twisting motion of thiadiazole core in the presence of amine, reducing significantly the nonradiative recombination pathways and subsequently enhancing the emission intensity. Credibly, nicotine regarded as a harmful chemical and bearing an amine pending group is also detected with high sensitivity, positioning this MOF as a potential sensor for practical environmental applications. This finding serves also as a benchmark to understand the sensing mechanism in MOFs.

An Electron-Rich Helical Host for the Exclusive Removal of a Planar Electron-Deficient Organic Compound.

In this study, a series of electron-rich helical hosts, viz. Pyr-HAC, Anth-HAC and Ben-HAC, containing pyrene, anthracene and benzene residues, respectively, at their periphery, were screened for their interaction with different planar electron-deficient organic guests (PEDOGs). A strong and highly selective charge-transfer interactions (CTI) was observed between the host Pyr-HAC and the guest 1,2,4,5-tetracyano-benzene (TCNB), leading to a yellow-to-bright-red color change in both the solubilized and the solid state. The interaction between Pyr-HAC and TCNB also induced profound structural and morphological changes. Pyr-HAC self-assembled into belt-like morphology created by homochiral stacking of the host molecules, but in the Pyr-HAC⊃TCNB complex, square bipyramids containing intertwined heterochiral C2 -double helices of Pyr-HAC were observed. Other PEDOGs did not induce any of the above changes in Pyr-HAC. Detailed UV/Vis absorption and fluorescence spectroscopy, NMR, and X-ray diffraction studies confirmed this selectivity, which arises due to CTI assisted by complementary, directional intermolecular hydrogen bonding (DIHB) between Pyr-HAC and TCNB. This allowed for the exclusive extraction of TCNB from a solution enriched in other PEDOGs. Thus, this study provides a ground work for designing responsive helical hosts towards CTI-driven selective "catch-and-release" of guests.

The effect of renal transplantation on left ventricular function, electrocardiography, and mechanical synchrony by gated myocardial perfusion imaging.

BACKGROUND: Depressed left ventricular ejection fraction (LVEF), LV mechanical dyssynchrony (LVMD), and prolonged QTc interval predict poor outcomes in end-stage renal disease (ESRD). Renal transplantation improves mortality in ESRD patients but the effects of transplantation on these indices remain undefined. METHODS: We identified patients with myocardial perfusion imaging (MPI) before and after renal transplantation. A control group consisted of ESRD patients who underwent 2 MPIs but did not receive a transplant. Changes in LVEF, LVMD indices [phase standard deviation (SD) and bandwidth (BW)] by MPI, and electrocardiogram (ECG) indices were determined. RESULTS: The study population consisted of 32 ESRD patients (53% male, 50 ± 11 years, 59% African American, 65% diabetic). The second MPI was performed 31 months (13-59 months) after renal transplantation. LVEF (72 ± 10% vs. 67 ± 10%, P < 0.001) but not SD (22 ± 15° vs. 22 ± 11°, P = 0.9) or BW (58 ± 35° vs. 57 ± 29°, P = 0.9) improved after transplantation. There were no changes in these indices in the control group. QTc (425 ± 30 ms vs. 447 ± 32 ms, P = <0.001) but not QRS (90 ± 21 ms vs. 90 ± 21 ms, P = 0.9) improved significantly after renal transplantation. CONCLUSIONS: LVEF and QTc improved after renal transplantation but LVMD indices and QRS did not change, which suggests that LVMD and electrical dyssynchrony may be irreversible in ESRD.

Achieving Superprotonic Conduction with a 2D Fluorinated Metal-Organic Framework.

A hydrolytically stable metal-organic framework (MOF) material, named KAUST-7', was derived from a structural phase change of KAUST-7 upon exposure to conditions akin to protonic conduction (363 K/95% relative humidity). KAUST 7' exhibited a superprotonic conductivity as evidenced by the impedance spectroscopic measurement revealing an exceptional conductivity up to 2.0 × 10-2 S cm-1 at 363 K and under 95% RH, a performance maintained over 7 days. Ab initio molecular dynamics simulations suggested that the water-mediated proton transport mechanism is governed by water assisted reorganization of the H-bond network involving the fluorine moieties in KAUST-7' and the guest water molecules. The notable level of performances combined with a very good hydrolytic stability positions KAUST-7' as a prospective proton-exchange membrane alternative to the commercial benchmark Nafion. Furthermore, the remarkable RH sensitivity of KAUST-7' conductivity, substantially higher than previously reported MOFs, offers great opportunities for deployment as a humidity sensor.

Management of Urinary Incontinence Following Suburethral Sling Removal.

PURPOSE: We evaluated urinary incontinence outcomes following synthetic suburethral sling removal in women. MATERIALS AND METHODS: We reviewed a prospectively maintained database of 360 consecutive women who underwent transvaginal suburethral sling removal from 2005 to 2015. We excluded patients with neurogenic bladder, nonsynthetic or multiple slings, prior mesh for prolapse, concomitant surgery during sling excision, urethral erosion or fistula, postoperative retention or less than 6-month followup. Demographics, sling type, indications for removal, time to removal and patient reported outcomes were recorded. Outcomes were stratified by incontinence type, including stress predominant, urge predominant and mixed urinary incontinence. Subsequent management was evaluated, including observation, minimally invasive outpatient interventions (bulking agents, neuromodulation or onabotulinumtoxinA) or more invasive surgery (autologous fascial sling or bladder suspension). No patients elected to receive a subsequent synthetic sling. Success was defined by responses to UDI-6 (Urogenital Distress Inventory) questions 2 and 3, self-reported satisfaction with continence at the last visit and no further intervention. RESULTS: Of the 99 patients who met inclusion criteria 27 denied any subjective leakage after suburethral sling removal alone while 72 experienced some degree of incontinence after removal. Stress predominant urinary incontinence occurred in 26 patients, which was persistent in 7 and de novo in 19, urge predominant incontinence was noted in 14, which was persistent in 6 and de novo in 8, and mixed urinary incontinence occurred in 32, which was persistent in 13 and de novo in 19. Mean followup was 23 months (range 6 to 114). The success rate following a single minimally invasive intervention after suburethral sling removal was 81%, 86% and 75% in patients with stress predominant, urge predominant and mixed urinary incontinence, respectively. CONCLUSIONS: Patients who undergo suburethral sling removal may show urinary control, or de novo or persistent incontinence with a higher predilection for stress predominant or mixed urinary incontinence. However, after a single minimally invasive intervention following suburethral sling removal the success rate reached 75% to 86%.

Underactive Bladder.

Underactive bladder (UAB) is a very common condition leading to disabling lower urinary tract symptoms. There has been an increasing interest in this condition as there is no effective treatment currently available. UAB has been described in many ways, but there is no agreed upon consensus on its terminology. The prevalence of UAB may be underestimated. This review focuses on the terminology, pathophysiology, common causes, its treatment, and future areas of research.

Giant Hysteretic Sorption of CO2 : In Situ Crystallographic Visualization of Guest Binding within a Breathing Framework at 298 K.

A dynamic ZnII -MOF has been shown to exhibit extreme breathing behavior under gas pressure. The very narrow pore form of the activated framework opens up in the presence of carbon dioxide, thus making it a suitable material for CO2 capture. Sorption of CO2 at 298 K and relatively high pressure clearly shows a two-step isotherm with giant hysteresis for the second step. In-situ single-crystal diffraction analysis was carried out under CO2 gas pressure at 298 K using an environmental gas cell in order to visualize the interaction between CO2 and the host framework. The results are well supported by pressure-gradient differential scanning calorimetry (P-DSC) and variable-pressure powder X-ray analysis. Theoretical calculations have been carried out in order to further back up the crystallographic data.

Anomalous Anisotropic Thermal Expansion in a One-Dimensional Coordination Polymer Driven by Conformational Flexibility.

A one-dimensional lithium(I) coordination polymer has been characterized by variable-temperature single-crystal X-ray diffraction and differential scanning calorimetry. This compound possesses an anisotropic packing arrangement that, along with a scissor-like or hingelike movement of the pyridyl ligand side arms, results in an extremely rare combination of positive, negative, and zero thermal expansion. Designing such types of materials and understanding the mechanistic details can facilitate the design of new thermoresponsive materials.

Generalized linear stability of non-inertial rimming flow in a rotating horizontal cylinder.

The stability of a thin film of viscous liquid inside a horizontally rotating cylinder is studied using modal and non-modal analysis. The equation governing the film thickness is derived within lubrication approximation and up to first order in aspect ratio (average film thickness to radius of the cylinder). Effect of gravity, viscous stress and capillary pressure are considered in the model. Steady base profiles are computed in the parameter space of interest that are uniform in the axial direction. A linear stability analysis is performed on these base profiles to study their stability to axial perturbations. The destabilizing behavior of aspect ratio and surface tension is demonstrated which is attributed to capillary instability. The transient growth that gives maximum amplification of any initial disturbance and the pseudospectra of the stability operator are computed. These computations reveal weak effect of non-normality of the operator and the results of eigenvalue analysis are recovered after a brief transient period. Results from nonlinear simulations are also presented which also confirm the validity of the modal analysis for the flow considered in this study.

Direct evidence for single-crystal to single-crystal switching of degree of interpenetration in a metal-organic framework.

A known doubly interpenetrated metal-organic framework with the formula [Zn2(ndc)2(bpy)] possesses minimal porosity when activated. We show not only that the material converts to its triply interpenetrated analogue upon desolvation, but also that the transformation occurs in a single-crystal to single-crystal manner under ambient conditions. The mechanism proposed for the conversion is supported by computational methods and by analogy with the solid-state behavior of an analogous system.

The prognostic value of left ventricular mechanical dyssynchrony using gated myocardial perfusion imaging in patients with end-stage renal disease.

BACKGROUND: Prior studies show that left ventricular mechanical dyssynchrony (LVD), measured by gated SPECT myocardial perfusion imaging (MPI), identifies patients with end-stage renal disease (ESRD) at higher risk for all-cause mortality but these were in small number of patients. We sought to assess the interaction between LVD and LV perfusion pattern in risk-stratification of a large sample size of patients with ESRD. METHODS: From the renal transplantation database maintained at the University of Alabama at Birmingham, we identified consecutive patients with ESRD who had gated SPECT MPI between 2003 and 2007. MPIs were reprocessed to derive LV ejection fraction (EF), perfusion defect size, and LVD [phase bandwidth (BW) and phase standard deviation (SD)]. The primary end-point was all-cause mortality, which was prospectively collected and verified against the social security death index database. RESULTS: There were 828 patients aged 52.6 ± 0.36 years (45% were women and 60% had diabetes mellitus). The LVEF was 54.8 ± 0.4% and the perfusion pattern was abnormal in 334 patients (41%). During a follow-up period of 61 ± 0.9 months, 230 patients (28%) received renal transplants and 290 patients (35%) died. The phase BW (73.1 ± 2.6° vs 66.3 ± 1.8°, P = .02) and SD (25.2 ± 0.8° vs 23.4 ± 0.5°, P = .06) were greater in patients who died than those who survived indicating greater dyssynchrony. Patients with phase BW >56° or SD ≥21° (median values) had worse 5-year survival (64% vs 72%, and 66% vs 71%, log-rank P = .005 and P = .07, respectively). After adjusting for demographics, co-morbidities, LVEF, and perfusion pattern, phase BW was associated with worse outcome (hazard ratio 1.289 95% CI 1.010-1.644, P = .04). CONCLUSIONS: LVD by phase analysis of gated SPECT MPI provides prognostic value in ESRD beyond myocardial perfusion and EF.

The relationship of left ventricular mechanical dyssynchrony and cardiac sympathetic denervation to potential sudden cardiac death events in systolic heart failure.

BACKGROUND: Patients with heart failure (HF) are at increased risk for left ventricular (LV) dyssynchrony which is associated with sudden cardiac death (SCD). This study examined the association of LV mechanical dyssynchrony and cardiac sympathetic denervation with potential SCD events in symptomatic patients with HF and reduced ejection fraction (HFrEF). METHODS: Of the 917 HFrEF patients in ADMIRE-HF, 92 experienced adjudicated potential SCD events during a 17 months median follow-up. Propensity scores were used to assemble a matched cohort of 85 pairs of patients with and without potential SCD events. ADMIRE-HF subjects had rest gated SPECT Tc-99m and I-123 MIBG imaging. Perfusion images were processed using phase analysis software to derive phase standard deviation (SD), an index of mechanical dyssynchrony. RESULTS: Of the 92 patients who experienced adjudicated potential SCD events 23 had SCD, 5 fatal myocardial infarction, 7 resuscitated cardiac arrest, 46 had appropriate ICD therapy, and 11 had sustained ventricular tachycardia. Patients who experienced potential SCD events had significantly wider phase SD than matched control patients (62.3 ± 2.4º vs 55.5 ± 2.3º, P = .03) and were more likely to have a phase SD ≥ 60º (53 % vs 35 %, P = .03). Fewer patients with potential SCD events (6 % vs 15 % of the controls, P = .08) had an MIBG heart/mediastinum uptake-ratio ≥1.6. CONCLUSIONS: Among symptomatic HFrEF patients, LV mechanical dyssynchrony is independently associated with potential SCD events. Phase analysis may provide incremental prognostic information on top of current indicators of SCD risk in HFrEF.

Should one go for individual- or group-level brain parcellations? A deep-phenotyping benchmark.

The analysis and understanding of brain characteristics often require considering region-level information rather than voxel-sampled data. Subject-specific parcellations have been put forward in recent years, as they can adapt to individual brain organization and thus offer more accurate individual summaries than standard atlases. However, the price to pay for adaptability is the lack of group-level consistency of the data representation. Here, we investigate whether the good representations brought by individualized models are merely an effect of circular analysis, in which individual brain features are better represented by subject-specific summaries, or whether this carries over to new individuals, i.e., whether one can actually adapt an existing parcellation to new individuals and still obtain good summaries in these individuals. For this, we adapt a dictionary-learning method to produce brain parcellations. We use it on a deep-phenotyping dataset to assess quantitatively the patterns of activity obtained under naturalistic and controlled-task-based settings. We show that the benefits of individual parcellations are substantial, but that they vary a lot across brain systems.

Individual Brain Charting dataset extension, third release for movie watching and retinotopy data.

The Individual Brain Charting (IBC) is a multi-task functional Magnetic Resonance Imaging dataset acquired at high spatial-resolution and dedicated to the cognitive mapping of the human brain. It consists in the deep phenotyping of twelve individuals, covering a broad range of psychological domains suitable for functional-atlasing applications. Here, we present the inclusion of task data from both naturalistic stimuli and trial-based designs, to uncover structures of brain activation. We rely on the Fast Shared Response Model (FastSRM) to provide a data-driven solution for modelling naturalistic stimuli, typically containing many features. We show that data from left-out runs can be reconstructed using FastSRM, enabling the extraction of networks from the visual, auditory and language systems. We also present the topographic organization of the visual system through retinotopy. In total, six new tasks were added to IBC, wherein four trial-based retinotopic tasks contributed with a mapping of the visual field to the cortex. IBC is open access: source plus derivatives imaging data and meta-data are available in public repositories.