Molecular Mix Research Articles

Do near-threshold molecular states mix with neighboring Q¯Q states?

The last two decades are marked by a renaissance in hadronic spectroscopy caused by the arrival of vast experimental information on exotic states in the spectrum of charmonium and bottomonium. Most of such states have properties at odds with the predictions of the quark model and reside very close to strong hadronic thresholds. Prominent examples are provided by the glorious $X(3872)$ charmonium-like state and the doubly charmed tetraquark $T_{cc}^+$ with the masses within less than 1 MeV from the $D\bar{D}^*$ and $DD^*$ open-charm thresholds, respectively. The universality of this feature hints towards the existence of a general pattern for such exotic states. In this work we discuss a possible generic mechanism for the formation of near-threshold molecular states as a result of the strong coupling of compact quark states with a hadronic continuum channel. The compact states that survive the strong coupling limit decouple from the continuum channel and therefore also from the formed hadronic molecule - if realised this scenario would provide a justification to treat hadronic molecules isolated, ignoring the possible influence from surrounding, compact quark-model states. We confront the phenomenology of the $D_{s1}(2460)$ and $D_{s1}(2536)$ with this picture and find consistency, although other explanations remain possible for those states.

Achieving High-Performance Molecular Rectification through Fast Screening Alkanethiol Carboxylate-Metal Complexes Electroactive Units

Achieving High-Performance Molecular Rectification through Fast Screening Alkanethiol Carboxylate-Metal Complexes Electroactive Units

Electrochromic Metallo–Organic Nanoscale Films: A Molecular Mix and Match Approach to Thermally Robust and Multistate Solid‐State Devices

AbstractIn this work, the performance of surface‐confined molecular assemblies, combined with a solid‐state electrolyte, as multicolor displays is reported. An ultraviolet (UV) crosslinked polymer is used as a matrix for the electrolyte. No dedicated ion storage layer is required to operate the laminated devices; up to 4500 redox cycles are demonstrated at a low voltage. The intense coloration and switching properties (t = 0.4–2.8 s) are retained even after thermally treating these devices at 100 °C for 24 h in air. The versatility of this approach is demonstrated by the use of spray‐coated bimolecular assemblies for multicolor display fabrication. The molecular assemblies have coloration efficiencies as high as 338 cm2 C−1.

Choice of mobile phase: Implications for size exclusion chromatography-inductively coupled plasma-mass spectrometry analyses of copper, zinc and iron metalloproteins

The correct identification of the metalloproteins present in human tissues and fluids is essential to our understanding of the cellular mechanisms underpinning a host of health disorders. Separation and analysis of biological samples are typically done via size exclusion chromatography hyphenated with inductively coupled plasma-mass spectrometry (SEC-ICP-MS). Although this technique can be extremely effective in identification of potential metalloproteins, the choice of mobile phase may have a marked effect on results, results by adversely affecting metal-protein bonds of the metalloproteins of interest. To assess the choice of mobile phase on SEC-ICP-MS resolution and the resulting metalloproteome pattern, we analysed several different sample types (brain homogenate; Cu/Zn-superoxide dismutase (SOD1); a molecular weight standard mix containing ferritin (Ft), ceruloplasmin (Cp), cytochrome c (CytC), vitamin B12 (B12) and thyroglobulin (Tg) using six different mobile phase conditions (200 mM, pH 7.5 solutions of ammonium salts nitrate, acetate, and sulfate; HEPES, MOPS and Tris-HCl). Our findings suggest that ammonium nitrate, ammonium acetate and Tris-HCl are optimal choices for the mobile phase, with the specific choice being dependent on both the number of samples and method of detection that is hyphenated with separation. Furthermore, we found that MOPS, HEPES and ammonium sulfate mobile phases all caused significant changes to peak resolution, retention time and overall profile shape. MOPS and HEPES, in particular, produced additional Fe peaks that were not detected with any of the other mobile phases that were investigated. As well as this, MOPS and HEPES both caused significant concentration dependent matrix suppression of the internal standard.

Three-dimensional simulations of turbulent mixing in spherical implosions

High-resolution large-eddy simulations of turbulent mixing at the inner surface of a dense shell which undergoes forced compression by a spherically imploding shock wave are presented. Perturbations on the inner surface grow as a result of Richtmyer-Meshkov and Rayleigh-Taylor instabilities and effects related to geometric convergence and compressibility. Three different cases with different initial surface perturbations, one broadband and two narrowband, are considered. The perturbation power spectrum is related to the mode number via Pℓ ∝ ℓn, where the case with broadband perturbations has n = −2, and modes in the range ℓ = 6–200. The narrowband perturbations have n = 0 and modes in the range ℓ = 50–100 and ℓ = 100–200. The simulations are carried out in spherical coordinates using the PLUTO hydrodynamics code. Results on the mix layer width, molecular mix, and turbulent kinetic energy distribution are presented, demonstrating clearly the impact of the amplitude and spectral form of the initial perturbation on the evolution of integral properties. A recently developed model predicting the growth of single mode perturbations in spherical implosions including shock waves is extended to predict mix layer amplitudes for broadband and narrowband cases, along with a model proposed by Mikaelian [“Rayleigh-Taylor and Richtmyer-Meshkov instabilities and mixing in stratified spherical shells,” Phys. Rev. A 42, 3400–3420 (1990)]. The resultant layer amplitude predictions from the new model are in good agreement with the numerical results while the longest wavelengths are not yet saturated, while Mikaelian’s model agrees well where the initial modes are saturated.

Methods of improving spatial resolution for IR spectroscopy in atmospheric-pressure plasma systems

High-temperature, atmospheric pressure plasma systems operated in molecular gases present complex diagnostic challenges. Infrared spectroscopy has been used to make measurements of the absorbance spectrum of complex molecular gas mixtures and thereby calculate the concentrations and species temperatures in these systems. For atmospheric-pressure systems, high spatial gradients arise and high spatial-resolution measurements are thus desirable. Some systems have achieved increased spatial resolution by reducing the beam diameter. However, this increase in spatial resolution comes at the expense of the optical throughput. Here we propose modifying a commercial Fourier Transform, Infrared spectrometer system with a set of simple optical elements. This design allows for scannable, high spatial resolution absorbance spectrum measurements of a complex molecular gas mix. We analyze the signal-to-noise ratio for this design and compare it with the diameter reduction method. For sufficiently low plasma radiation levels, this design improves the signal-to-noise ratio relative to reducing the beam diameter size while transmitting nearly all of the beam power. However, whether this design can achieve the desired sub-mm spatial resolution depends on the radiating area of the infrared light source in the spectrometer.

Detection of feline Coronavirus in effusions of cats with and without feline infectious peritonitis using loop-mediated isothermal amplification

Feline infectious peritonitis (FIP) is a fatal disease in cats worldwide. The aim of this study was to test two commercially available reaction mixtures in a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect feline Coronavirus (FCoV) in body cavity effusions of cats with and without FIP, in order to minimize the time from sampling to obtaining results.RNA was extracted from body cavity effusion samples of 71 cats, including 34 samples from cats with a definitive diagnosis of FIP, and 37 samples of control cats with similar clinical signs but other confirmed diseases. Two reaction mixtures (Isothermal Mastermix, OptiGene Ltd.and PCRun™ Molecular Detection Mix, Biogal) were tested using the same primers, which were designed to bind to a conserved region of the FCoV membrane protein gene. Both assays were conducted under isothermal conditions (61 °C–62 °C). Using the Isothermal Mastermix of OptiGene Ltd., amplification times ranged from 4 and 39 min with a sensitivity of 35.3% and a specificity of 94.6% for the reported sample group. Using the PCRun™ Molecular Detection Mix of Biogal, amplification times ranged from 18 to 77 min with a sensitivity of 58.8% and a specificity of 97.3%.Although the RT-LAMP assay is less sensitive than real time reverse transcription PCR (RT-PCR), it can be performed without the need of expensive equipment and with less hands-on time. Further modifications of primers might lead to a suitable in-house test and accelerate the diagnosis of FIP.

In vitro structure-specific Zn(II)-induced adipogenesis and structure-function bioreactivity correlations

The advent of Zn(II) metallodrugs in metabolic syndrome pathologies generates a strong challenge toward synthetic endeavors targeting well-defined, atoxic and biologically active binary/ternary species of Zn(II). Proper formulation of that metal ion's coordination sphere sets the stage for construction of appropriately configured Schiff ligands based on tromethamine and variably modified vanillin core components. The arising Schiff ligands react with Zn(II) in a defined stoichiometry, thereby delivering new binary Zn(II)-L species with defined physicochemical properties. Analytical (elemental), spectroscopic (FT-IR, Thermogravimetric Analysis) and crystallographic techniques attest to the distinct nature of the derived binary-ternary materials, bearing defined Zn(II):L molecular stoichiometry, variable nuclearity, charge, bulk and balance mix of hydrophilicity-hydrophobicity, thereby providing the physicochemical profile based on which biological studies could ensue. The structurally based selection of species was applied onto in vitro 3T3-L1 cultures, essentially exploring toxicity, migration, morphology, cell differentiation and maturation. The systematic effort toward comparative work on appropriately defined Zn(II) species and insulin in inducing adipogenesis reveals the salient structural features in the Schiff family of ligands configuring Zn(II) so as to promote complex formation sufficient to engage biomolecular targets during the process of initiation and maturation. Molecular targets of importance in adipogenesis were examined under the influence of Zn(II) and their expression levels suggest the structural composition that a Zn(II) ion might have to optimally pursue cell differentiation. Thus, a well-defined selection of binary Zn(II)-L species is tightly associated with the incurred bioactivity, thereby setting the stage for the development of efficient Zn(II) metallodrugs to combat Diabetes mellitus II.

The inherent dynamics of a molecular liquid: Geodesic pathways through the potential energy landscape of a liquid of linear molecules

Because the geodesic pathways that a liquid follows through its potential energy landscape govern its slow, diffusive motion, we suggest that these pathways are logical candidates for the title of a liquid's "inherent dynamics." Like their namesake "inherent structures," these objects are simply features of the system's potential energy surface and thus provide views of the system's structural evolution unobstructed by thermal kinetic energy. This paper shows how these geodesic pathways can be computed for a liquid of linear molecules, allowing us to see precisely how such molecular liquids mix rotational and translational degrees of freedom into their dynamics. The ratio of translational to rotational components of the geodesic path lengths, for example, is significantly larger than would be expected on equipartition grounds, with a value that scales with the molecular aspect ratio. These and other features of the geodesics are consistent with a picture in which molecular reorientation adiabatically follows translation-molecules largely thread their way through narrow channels available in the potential energy landscape.

Sphingolipid symmetry governs membrane lipid raft structure

Lipid domain formation in membranes underlies the concept of rafts but their structure is controversial because the key role of cholesterol has been challenged. The configuration of glycosphingolipid receptors for agonists, bacterial toxins and enveloped viruses in plasma membrane rafts appears to be an important factor governing ligand binding and infectivity but the details are as yet unresolved. I have used X-ray diffraction methods to examine how cholesterol affects the distribution of glycosphingolipid in aqueous dispersions of an equimolar mixture of cholesterol and egg-sphingomyelin containing different proportions of glucosylceramide from human extracts. Three coexisting liquid-ordered bilayer structures are observed at 37°C in mixtures containing up to 20mol% glycosphingolipid. All the cholesterol was sequestered in one bilayer with the minimum amount of sphingomyelin (33mol%) to prevent formation of cholesterol crystals. The other two bilayers consisted of sphingomyelin and glucosylceramide. Asymmetric molecular species of glucosylceramide with N-acyl chains longer than 20 carbons form an equimolar complex with sphingomyelin in which the glycosidic residues are arranged in hexagonal array. Symmetric molecular species mix with sphingomyelin in proportions less than equimolar to form quasicrystalline bilayers. When the glycosphingolipid exceeds equimolar proportions with sphingomyelin cholesterol is incorporated into the structure and formation of a gel phase of glucosylceramide is prevented. The demonstration of particular structural features of ceramide molecular species combined with the diversity of sugar residues of glycosphingolipid classes paves the way for a rational approach to understanding the functional specificity of lipid rafts and how they are coupled across cell membranes.

Ruthenium dihydroxybipyridine complexes are tumor activated prodrugs due to low pH and blue light induced ligand release

Ruthenium drugs are potent anti-cancer agents, but inducing drug selectivity and enhancing their modest activity remain challenging. Slow Ru ligand loss limits the formation of free sites and subsequent binding to DNA base pairs. Herein, we designed a ligand that rapidly dissociates upon irradiation at low pH. Activation at low pH can lead to cancer selectivity, since many cancer cells have higher metabolism (and thus lower pH) than non-cancerous cells. We have used the pH sensitive ligand, 6,6′-dihydroxy-2,2′-bipyridine (66′bpy(OH)2), to generate [Ru(bpy)2(66′(bpy(OH)2)]2+, which contains two acidic hydroxyl groups with pKa1=5.26 and pKa2=7.27. Irradiation when protonated leads to photo-dissociation of the 66′bpy(OH)2 ligand. An in-depth study of the structural and electronic properties of the complex was carried out using X-ray crystallography, electrochemistry, UV/visible spectroscopy, and computational techniques. Notably, RuN bond lengths in the 66′bpy(OH)2 complex are longer (by ~0.3Å) than in polypyridyl complexes that lack 6 and 6′ substitution. Thus, the longer bond length predisposes the complex for photo-dissociation and leads to the anti-cancer activity. When the complex is deprotonated, the 66′bpy(O−)2 ligand molecular orbitals mix heavily with the ruthenium orbitals, making new mixed metal–ligand orbitals that lead to a higher bond order. We investigated the anti-cancer activities of [Ru(bpy)2(66′(bpy(OH)2)]2+, [Ru(bpy)2(44′(bpy(OH)2)]2+, and [Ru(bpy)3]2+ (44′(bpy(OH)2=4,4′-dihydroxy-2,2′-bipyridine) in HeLa cells, which have a relatively low pH. It is found that [Ru(bpy)2(66′(bpy(OH)2)]2+ is more cytotoxic than the other ruthenium complexes studied. Thus, we have identified a pH sensitive ruthenium scaffold that can be exploited for photo-induced anti-cancer activity.

Genetic Analysis of the Hox Hydrogenase in the Cyanobacterium Synechocystis sp. PCC 6803 Reveals Subunit Roles in Association, Assembly, Maturation, and Function

Hydrogenases are metalloenzymes that catalyze 2H(+) + 2e(-) ↔ H(2). A multisubunit, bidirectional [NiFe]-hydrogenase has been identified and characterized in a number of bacteria, including cyanobacteria, where it is hypothesized to function as an electron valve, balancing reductant in the cell. In cyanobacteria, this Hox hydrogenase consists of five proteins in two functional moieties: a hydrogenase moiety (HoxYH) with homology to heterodimeric [NiFe]-hydrogenases and a diaphorase moiety (HoxEFU) with homology to NuoEFG of respiratory Complex I, linking NAD(P)H ↔ NAD(P)(+) as a source/sink for electrons. Here, we present an extensive study of Hox hydrogenase in the cyanobacterium Synechocystis sp. PCC 6803. We identify the presence of HoxEFUYH, HoxFUYH, HoxEFU, HoxFU, and HoxYH subcomplexes as well as association of the immature, unprocessed large subunit (HoxH) with other Hox subunits and unidentified factors, providing a basis for understanding Hox maturation and assembly. The analysis of mutants containing individual and combined hox gene deletions in a common parental strain reveals apparent alterations in subunit abundance and highlights an essential role for HoxF and HoxU in complex/subcomplex association. In addition, analysis of individual and combined hox mutant phenotypes in a single strain background provides a clear view of the function of each subunit in hydrogenase activity and presents evidence that its physiological function is more complicated than previously reported, with no outward defects apparent in growth or photosynthesis under various growth conditions.

Characterization of a 2.6 μm Kinetex porous shell hydrophilic interaction liquid chromatography column in supercritical fluid chromatography with a comparison to 3 μm totally porous silica

The first systematic study of the performance of a porous shell, hydrophylic interaction liquid chromatography (HILIC) column in supercritical fluid chromatography (SFC) is presented. Observed efficiency on 2.6-μm porous shell particles exceeded all reports using UHPLC on 100-mm long columns packed with <2-μm totally porous particles. A Kinetex 4.6 × 150 mm, 2.6 μm HILIC column significantly outperformed a 3 μm Luna totally porous silica of the same length and diameter. A 17 component, low molecular weight test mix, consisting of a range of small drug-like molecules was separated isocratically on each column, with similar selectivity, but the porous shell column required ½ the time (≈2 min vs. 4 min), with almost 50% higher efficiency. Even little retained compounds ( k < 0.5) exhibited more than 30,000 plates under some conditions. Reduced plate heights were higher than previously reported on porous shell particles in both HILIC and rHPLC, with the lowest value of 1.62. Significant fronting was sometimes observed. The cause of the fronting was not determined. The least symmetrical peaks showed the highest apparent efficiency. Pressure drop at optimum velocity (2.5 ml/min) and low modifier concentrations was <60 bar, and only exceeded 250 bar at near double optimum flow and 65% modifier. Peak widths were mostly just over 0.01 min (20 Hz) wide. There was a loss of efficiency when the injection volume was increased. The chromatograph was shown to have extremely low extra-column dispersion, on the order of 5–10 μL 2, which is also the lowest reported in an SFC, in spite of using standard components. This is likely due to turbulent flow in the tubing and fittings.

Atomic force microscopy study of immunosensor surface to scale down the size ofELISA-type sensors

Here we describe the use of atomic force microscopy (AFM) to study the nanoscalemechanics of the molecular layers of a popular immunosensor, ELISA (enzyme-linkedimmunosorbent assay) type. We characterize the sensor surface in terms of brush lengthand grafting density of the molecular layers. The obtained data demonstrated that areliable reading of the immunosignal (a suggested dimensionless combinationof brush length and grafting density) can be attained from an area as small as ∼ 3 µm2. This is approximately 4 million times smaller compared to typical ELISA sensors. Theimmunosensor described is composed of a molecular mix of two different antigens.Intriguingly, we find that AFM can reliably distinguish between having the immunosignalfrom either antibody and from both antibodies together. This was impossible to get byusing standard optical detection methods.

Symmetry lowering of pentacene molecular states interacting with a Cu surface

Pentacene adsorbed on the Cu(119) vicinal surface forms long-range ordered chain structures. Photoemission spectroscopy measurements and ab initio density functional theory simulations provide consistent evidences that pentacene molecular orbitals mix with the copper bands, giving rise to interaction states localized at the interface. Angular-resolved and polarization dependent photoemission spectroscopy shows that most of the pentacene derived intensity is strongly dichroic. The symmetry of the molecular states of the free pentacene molecules is reduced upon adsorption on Cu(119), as a consequence of the molecule-metal interaction. Theoretical results show a redistribution of the charge density in $\ensuremath{\pi}$ molecular states close to the Fermi level, consistent with the photoemission intensities (density of states) and polarization dependence (orbital symmetry).

How do smectic liquid crystals of different molecular length mix in thin films?

We present a model for the structure of binary mixtures of smectic compounds in freely suspended films of 2-7 layers. The compounds are the hexyl (6AB) and dodecyl (10AB) homologues of p, p'-dialkylazoxybenzene that differ by about 40% in molecular length. X-ray reflectivity indicates that no demixing occurs between 6AB and 10AB molecules, while also there is no indication found of increased roughness at the film surfaces. However, the surface layers are somewhat expanded compared to the interior layers. This can be explained by backfolding of the dodecyl end chains of 10AB molecules at the surface via two gauche kinks, which ensures dense packing. This model is supported by surface tension measurements that indicate an increased amount of alkyl groups at the surfaces.

Spectral measurements of Rayleigh–Taylor mixing at small Atwood number

Temperature measurements have been made in a buoyancy driven mixing layer created by an unstable temperature gradient in water. Experiments were performed with a temperature difference of 5 °C, with a corresponding Atwood number of 7.5×10−4. Two types of analyses were used to determine density fluctuation correlations. The first analysis determined density fluctuation correlations from the mean density profiles, which is sufficient for a two-fluid distribution of the density where there was no molecular mixing. The second analysis used measurements taken from a continuous distribution of density, and thus included molecular mixing associated with heat diffusion. The thermocouples used for temperature measurements enabled the collection of large sample sizes and thus a detailed examination of molecular mix fractions, spectral properties of the density fluctuations, and probability distributions of the density through the mixing layer.

Ion/Ion Reactions for Oligopeptide Mixture Analysis: Application to Mixtures Comprised of 0.5–100 kDa Components

Oligopeptide mixtures have been subjected to electrospray ionization, accumulated within a quadrupole ion trap, and subjected to ion/ion proton transfer reactions with anions derived from perfluoro-1,3-dimethylcyclohexane. Various mixtures were studied with approximate molecular weight ranges of 0.5–8.5, 12–30, 45–100, and 0.5–100 kDa. Mixtures of known composition were studied to evaluate the mixture complexity amenable to electrospray combined with ion/ion reactions to reduce spectral complexity associated with multiple charging. Mixture analysis with at least 40 components of low and medium molecular weight and roughly comparable solution concentrations appears to be straightforward. No matrix effects upon ionization were implicated in the data for the low and medium molecular weight mixtures but bovine albumin appeared to inhibit signals from bovine transferrin and chicken conalbumin in the high molecular weight mix. Furthermore, the presence of abundant low mass-to-charge ions appeared to inhibit signals from high molecular weight proteins (>40 kDa) in the 0.5–100 kDa mix. Such an observation is consistent with dynamic range limitations that can arise from discrimination based on ion space charge effects, although an ionization matrix effect could not be precluded from the data reported here. The results reported here indicate that the limitation to mixture complexity amenable to electrospray mass spectrometry imposed by spectral congestion associated with multiple charging can be significantly reduced via ion/ion reactions. The use of ion/ion reactions can therefore facilitate the study of other factors that can impose limitations to mixture analysis, such as matrix effects upon ionization and differences in ion transmission, accumulation, storage, and detection efficiencies.

Large and Small Scale Structure in Rayleigh-Taylor Mixing

Laser-induced fluorescence is used to image the central plane of the mix region of two immiscible liquids subject to the Rayleigh-Taylor instability at an acceleration of 70 times Earth's gravity. The size of the mixing zone grows with coefficient ${\ensuremath{\alpha}}_{b}\ensuremath{\gtrsim}0.054$. Individual bubbles are clearly resolved and their structure is measured. The widths of the bubbles are narrower than recent models predict. An internal structure in the bubbles appears after the mixing zone is established. This structure suggests a cascade to small wavelengths. The cascade is required for molecular mix.