Comprehending the Formation of Eutectics and Cocrystals in Terms of Design and Their Structural Interrelationships

The phenomenon of cocrystallization, which encompasses the art of making multicomponent organic solids such as cocrystals, solid solutions, eutectics, etc. for novel applications, has been less studied in terms of reliably and specifically obtaining a desired cocrystallization product and the issues that govern their formation. Further, the design, structural, and functional aspects of organic eutectics have been relatively unexplored as compared to solid solutions and cocrystals well-established by crystal engineering principles. Recently, eutectics were proposed to be designable materials on par with cocrystals, and herein we have devised a systematic approach, based on the same crystal engineering principles, to specifically and desirably make both eutectics and cocrystals for a given system. The propensity for strong homomolecular synthons over weak heteromolecular synthons and vice versa during supramolecular growth was successfully utilized to selectively obtain eutectics and cocrystals, respectively, in two model systems and in two drug systems. A molecular level understanding of the formation of eutectics and cocrystals and their structural interrelationships which is significant from both fundamental and application viewpoints is discussed. On the other hand, the obscurity in establishing a low melting combination as a eutectic or a cocrystal is resolved through phase diagrams.

Nonlinear preconditioning for efficient and accurate interface capturing in simulation of multicomponent compressible flows

Single fluid schemes that rely on an interface function for phase identification in multicomponent compressible flows are widely used to study hydrodynamic flow phenomena in several diverse applications. Simulations based on standard numerical implementation of these schemes suffer from an artificial increase in the width of the interface function owing to the numerical dissipation introduced by an upwind discretization of the governing equations. In addition, monotonicity requirements which ensure that the sharp interface function remains bounded at all times necessitate use of low-order accurate discretization strategies. This results in a significant reduction in accuracy along with a loss of intricate flow features. In this paper we develop a nonlinear transformation based interface capturing method which achieves superior accuracy without compromising the simplicity, computational efficiency and robustness of the original flow solver. A nonlinear map from the signed distance function to the sigmoid type interface function is used to effectively couple a standard single fluid shock and interface capturing scheme with a high-order accurate constrained level set reinitialization method in a way that allows for oscillation-free transport of the sharp material interface. Imposition of a maximum principle, which ensures that the multidimensional preconditioned interface capturing method does not produce new maxima or minima even in the extreme events of interface merger or breakup, allows for an explicit determination of the interface thickness in terms of the grid spacing. A narrow band method is formulated in order to localize computations pertinent to the preconditioned interface capturing method. Numerical tests in one dimension reveal a significant improvement in accuracy and convergence; in stark contrast to the conventional scheme, the proposed method retains its accuracy and convergence characteristics in a shifted reference frame. Results from the test cases in two dimensions show that the nonlinear transformation based interface capturing method outperforms both the conventional method and an interface capturing method without nonlinear transformation in resolving intricate flow features such as sheet jetting in the shock-induced cavity collapse. The ability of the proposed method in accounting for the gravitational and surface tension forces besides compressibility is demonstrated through a model fully three-dimensional problem concerning droplet splash and formation of a crownlike feature. (C) 2014 Elsevier Inc. All rights reserved.

Finite size scaling in crossover among different random matrix ensembles in microscopic lattice models

Using numerical diagonalization we study the crossover among different random matrix ensembles (Poissonian, Gaussian orthogonal ensemble (GOE), Gaussian unitary ensemble (GUE) and Gaussian symplectic ensemble (GSE)) realized in two different microscopic models. The specific diagnostic tool used to study the crossovers is the level spacing distribution. The first model is a one-dimensional lattice model of interacting hard-core bosons (or equivalently spin 1/2 objects) and the other a higher dimensional model of non-interacting particles with disorder and spin-orbit coupling. We find that the perturbation causing the crossover among the different ensembles scales to zero with system size as a power law with an exponent that depends on the ensembles between which the crossover takes place. This exponent is independent of microscopic details of the perturbation. We also find that the crossover from the Poissonian ensemble to the other three is dominated by the Poissonian to GOE crossover which introduces level repulsion while the crossover from GOE to GUE or GOE to GSE associated with symmetry breaking introduces a subdominant contribution. We also conjecture that the exponent is dependent on whether the system contains interactions among the elementary degrees of freedom or not and is independent of the dimensionality of the system.

Temperature-Induced Reversible First-Order Single Crystal to Single Crystal Phase Transition in Boc-gamma(4)(R)Val-Val-OH: Interplay of Enthalpy and Entropy

Crystals of Boc-gamma y(4)(R)Val-Val-OH undergo a reversible first-order single crystal to single crystal phase transition at T-c approximate to 205 K from the orthorhombic space group P22(1)2(1) (Z' = 1) to the monoclinic space group P2(1) (Z' = 2) with a hysteresis of similar to 2.1 K. The low-temperature monoclinic form is best described as a nonmerohedral twin with similar to 50% contributions from its two components. The thermal behavior of the dipeptide crystals was characterized by differential scanning calorimetry experiments. Visual changes in birefringence of the sample during heating and cooling cycles on a hot-stage microscope with polarized light supported the phase transition. Variable-temperature unit cell check measurements from 300 to 100 K showed discontinuity in the volume and cell parameters near the transition temperature, supporting the first-order behavior. A detailed comparison of the room-temperature orthorhombic form with the low-temperature (100 K) monoclinic form revealed that the strong hydrogen-bonding motif is retained in both crystal systems, whereas the non-covalent interactions involving side chains of the dipeptide differ significantly, leading to a small change in molecular conformation in the monoclinic form as well as a small reorientation of the molecules along the ac plane. A rigid-body thermal motion analysis (translation, libration, screw; correlation of translation and libration) was performed to study the crystal entropy. The reversible nature of the phase transition is probably the result of an interplay between enthalpy and entropy: the low-temperature monoclinic form is enthalpically favored, whereas the room-temperature orthorhombic form is entropically favored.

Wallner lines, crack velocity and mechanisms of crack nucleation and growth in a brittle bulk metallic glass

Mode I fracture experiments were conducted on brittle bulk metallic glass (BMG) samples and the fracture surface features were analyzed in detail to understand the underlying physical processes. Wollner lines, which result from the interaction between the propagating crack front and shear waves emanating from a secondary source, were observed on the fracture surface and geometric analysis of them indicates that the maximum crack velocity is similar to 800 m s(-1), which corresponds to similar to 0.32 times the shear wave speed. Fractography reveals that the sharp crack nucleation at the notch tip occurs at the mid-section of the specimens with the observation of flat and half-penny-shaped cracks. On this basis, we conclude that the crack initiation in brittle BMGs is stress-controlled and occurs through hydrostatic stress-assisted cavity nucleation ahead of the notch tip. High magnification scanning electron and atomic force microscopies of the dynamic crack growth regions reveal highly organized, nanoscale periodic patterns with a spacing of similar to 79 nm. Juxtaposition of the crack velocity with this spacing suggests that the crack takes similar to 10(-10) s for peak-to-peak propagation. This, and the estimated adiabatic temperature rise ahead of the propagating crack tip that suggests local softening, is utilized to critically discuss possible causes for the nanocorrugation formation. Taylor's fluid meniscus instability is unequivocally ruled out. Then, two other possible mechanisms, viz. (a) crack tip blunting and resharpening through nanovoid nucleation and growth ahead of the crack tip and eventual coalescence, and (b) dynamic oscillation of the crack in a thin slab of softened zone ahead of the crack-tip, are critically discussed. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characterization of Interactions Involving Bromine in 2,2-Dibromo2,3-dihydroinden-1-one via Experimental Charge Density Analysis

Experimental and theoretical charge density analyses on 2,2-dibromo-2,3-dihydroinden-1-one have been carried out to quantify the topological features of a short CBr....O halogen bond with nearly linear geometry (2.922 angstrom, angle CBr....O = 172.7 degrees) and to assess the strength of the interactions using the topological features of the electron density. The electrostatic potential map indicates the presence of the s-hole on bromine, while the interaction energy is comparable to that of a moderate OH....O hydrogen bond. In addition, the energetic contribution of CH.....Br interaction is demonstrated to be on par with that of the CBr....O halogen bond in stabilizing the crystal structure.

Observation of a reversible isomorphous phase transition and an interplay of ``sigma-holes'' and ``pi-holes'' in Fmoc-Leu-psiCH2-NCS]

Fmoc-Leu-psiCH2NCS] undergoes a reversible isomorphous phase transition upon cooling. The crystal structure at 100 K displays a short N=C=S center dot center dot center dot N=C=S intermolecular interaction, which has been characterized based on experimental charge density analysis, as a stabilizing interaction with both sigma-holes and pi-holes acting cooperatively.

Experimental validation of `pnicogen bonding' in nitrogen by charge density analysis

The participation of a nitrogen atom acting as an electrophile in pnicogen bonding, a hitherto unexplored interaction has been established by experimental charge density analysis. QTAIM and NBO analyses ratify this observation.

Optically transparent polymer devices for in situ assessment of cell electroporation

In order to study cell electroporation in situ, polymer devices have been fabricated from poly-dimethyl siloxane with transparent indium tin oxide parallel plate electrodes in horizontal geometry. This geometry with cells located on a single focal plane at the interface of the bottom electrode allows a longer observation time in both transmitted bright-field and reflected fluorescence microscopy modes. Using propidium iodide (PI) as a marker dye, the number of electroporated cells in a typical culture volume of 10-100 mu l was quantified in situ as a function of applied voltage from 10 to 90 V in a series of 2-ms pulses across 0.5-mm electrode spacing. The electric field at the interface and device current was calculated using a model that takes into account bulk screening of the transient pulse. The voltage dependence of the number of electroporated cells could be explained using a stochastic model for the electroporation kinetics, and the free energy for pore formation was found to be kT at room temperature. With this device, the optimum electroporation conditions can be quickly determined by monitoring the uptake of PI marker dye in situ under the application of millisecond voltage pulses. The electroporation efficiency was also quantified using an ex situ fluorescence-assisted cell sorter, and the morphology of cultured cells was evaluated after the pulsing experiment. Importantly, the efficacy of the developed device was tested independently using two cell lines (C2C12 mouse myoblast cells and yeast cells) as well as in three different electroporation buffers (phosphate buffer saline, electroporation buffer and 10 % glycerol).

Revalidation of Natrix clerki Wall, 1925, an overlooked species in the genus Amphiesma Dumeril, Bibron & Dumeril, 1854 (Squamata: Natricidae)

Natrix clerki Wall, 1925, previously known from its sole holotype and considered a synonym of Amphiesma parallelum (Boulenger, 1890), is resurrected in the genus Amphiesma on the basis of the analysis of morphological variation in 28 specimens of ``Amphiesma parallelum'' auctorum, plus six living, unvouchered specimens discovered in Arunachal Pradesh and Nagaland, India, and one vouchered specimen from Talle Valley in Arunachal Pradesh. Specimens from northeast India (Nagaland), northern Myanmar, and China (Yunnan), previously identified as Amphiesma parallelum either in the literature or in museum's catalogues, are also here referred to A. clerki. The holotype of Amphiesma clerki is redescribed. As a consequence, the definition of Amphiesma parallelum is modified. A. parallelum inhabits the Khasi Hills and Naga Hills in Northeast India, whereas A. clerki has a wider range in the Eastern Himalayas, northern Myanmar and Yunnan (China). Amphiesma clerki differs from A. parallelum by its longer tail, dorsal scales more strongly keeled, scales of the first dorsal scale row strongly keeled vs. smooth, a postocular streak not interrupted at the level of the neck, and a much more vivid pattern on a darker background colour. Characters of species of the Amphiesma parallelum group, i.e. A. clerki, A. parallelum, A. bitaeniatum, A. platyceps and A. sieboldii are compared. A key to this group is provided.

A delocalizable cationic headgroup together with an oligo-oxyethylene spacer in gemini cationic lipids improves their biological activity as vectors of plasmid DNA

Lipoplex nano-aggregates constituted of plasmid DNA (pDNA) pEGFP-C3 and mixed cationic liposomes, consisting of several percentages of a gemini cationic lipid (GCL) of the 1,2-bis(hexadecyl imidazolium) oxyethylene series, referred to as (C(16)Im)(2)(C2O)(n), with oxyethylene spacers (n = 1, 2 or 3) between the imidazolium cationic groups and the DOPE zwitterionic helper lipid, have been characterized by various biophysical and biological approaches carried out at several GCL compositions (alpha), and either the mass or the effective charge ratio of the lipoplex. The electrochemical study by zeta-potential confirms that the three GCLs yield a 10% lower effective charge than the nominal one, while compacted pDNA yields only a 25% effective negative charge. The SAXS study reveals, irrespective of the spacer length (n) and effective charge ratio (rho(eff)), the presence of two lamellar structures, i.e., one (L-alpha,L-main) in the whole GCL composition and another (L-alpha,L-DOPE,L-rich) with higher periodicity values that coexists with the previous one at low GCL composition (alpha = 0.2). The cryo-TEM analysis shows two types of multilamellar structures consisting of cationic lipidic bilayers with pDNA sandwiched between them: a cluster-type (C-type) at low alpha = 0.2 and a fingerprint-type (FP-type) at alpha >= 0.5, both with similar interlamellar spacing (d) in agreement with the L-alpha,L-main structure determined by SAXS. Transfection efficacies (TEs) of each lipid mixture were determined in four different cell lines (HEK293T, HeLa, Caco-2 and A549) at several alpha and rho(eff) values in the absence and presence of serum (FBS). The optimized formulations (alpha = 0.2 and rho(eff) = 2.0) substantially transfect cells much better than a commercial transfection reagent, Lipofectamine 2000 and previously studied efficient lipoplexes containing other cationic head groups or spacers both in the absence and presence of serum. The activity of optimized formulations may be attributed to the combination of several factors, such as: (a) the fusogenic character of DOPE which results in higher fluidity of the lipoplexes at alpha = 0.2, (b) the coexistence of two lamellar structures at alpha = 0.2 that synergizes the TE of these lipid vectors, and mainly (c) the higher biocompatibility of the GCLs reported in this work due to the presence of two imidazolium cationic groups together with an oligo-oxyethylene spacer. The length of the spacer in the GCL seems to have less impact, although (C(16)Im)(2)(C2O)(n)/DOPEpDNA lipoplexes with n = 1 and 3 show higher gene transfection than n = 2. All the optimum formulations reported herein are all highly efficient with negligible levels of toxicity, and thus, may be considered as very promising gene vectors for in vivo applications.

Crystal landscape in the orcinol:4,4 `-bipyridine system: synthon modularity, polymorphism and transferability of multipole charge density parameters

Polymorphism in the orcinol: 4,4'-bipyridine cocrystal system is analyzed in terms of a robust convergent modular phenol...pyridine supramolecular synthon. Employing the Synthon Based Fragments Approach (SBFA) to transfer the multipole charge density parameters, it is demonstrated that the crystal landscape can be quantified in terms of intermolecular interaction energies in the five crystal forms so far isolated in this complex system. There are five crystal forms. The first has an open, divergent O-H...N based structure with alternating orcinol and bipyridine molecules. The other four polymorphs have different three-dimensional packing but all of them are similar at an interaction level, and are based on a modular O-H...N mediated supramolecular synthon that consists of two orcinol and two bipyridine molecules in a closed, convergent structure. The SBFA method, which depends on the modularity of synthons, provides good agreement between experiment and theory because it takes into account the supramolecular contribution to charge density. The existence of five crystal forms in this system shows that polymorphism in cocrystals need not be considered to be an unusual phenomenon. Studies of the crystal landscape could lead to an understanding of the kinetic pathways that control the crystallization processes, in other words the valleys in the landscape. These pathways are traditionally not considered in exercises pertaining to computational crystal structure prediction, which rather monitors the thermodynamics of the various stable forms in the system, in other words the peaks in the landscape.

Effect of viscosity contrast on plume formation in density stratified fluids

We perform two and three dimensional numerical simulations of plume formation in density and viscosity stratified fluid systems. We show that the ambient to plume fluid viscosity ratio strongly affects the near wall plume structures (line or sheet plumes) such as plume spacing and shape of plumes. We observe that where mushroom-like plumes are observed for lower viscosity ratios, taller plumes with bulbous heads form for high viscosity ratios. Plume structure and spacing are in good agreement with experimental results. By studying the geometry of the line plumes and the flow in the circulation cells, we discuss the mechanisms of their formation and the dynamics of merging. We show that an increase in the viscosity ratio decreases the total length of line plumes in the planform which indicates a decreased mixing at higher viscosity ratios. (C) 2015 Elsevier Ltd. All rights reserved.

Halogen Bonding and Chalcogen Bonding in 4,7-Dibromo-5, 6-dinitro-2,1,3-benzothiadiazole

An organic solid, 4,7-dibromo-5,6-dinitro-2,1,3-benzothiadiazole, has been designed to serve as an illustrative example to quantitatively evaluate the relative merits of halogen and chalcogen bonding in terms of charge density features. The compound displays two polymorphic modifications, one crystallizing in a non-centrosymmetric space group (Z' = 1) and the other in a centrosymmetric space group with two molecules in the asymmetric unit (Z' = 2). Topological analysis based on QTAIM clearly brings out the dominance of the chalcogen bond over the halogen bond along with an indication that halogen bonds are more directional compared to chalcogen bonds. The cohesive energies calculated with the absence of both strong and weak hydrogen bonds as well as stacking interaction are indicative of the stabilities associated with the polymorphic forms.