Unsolvable Phase Research Articles

Quantum computational, solvation and in-silico biological studies of a potential anti-cancer thiophene derivative

Heterocyclic molecules display a wide spectrum of properties that span both material and biological domains. Material properties stem from their interactions in the bulk, where a large number of molecules of the same type get together resulting in an enhancement of properties. However, biological properties emanate from the interaction of a single or a few molecules with a biologically functional macromolecule. Computational tools offer a particularly useful way of theoretically studying molecules to arrive at a conclusion regarding such properties, even though they may vary when experimentally evaluated. This study concerns itself with the theoretical investigation comprising density functional theory calculations, topological analyses and in-silico biological evaluation of a thiophene compound, i.e. the title compound. Density functional theory was used to compute properties of the title molecule and their variations in unsolvated and solvated phases using Gaussian 09. The molecule in solvent phases encompassing organic polar protic, organic polar aprotic and inorganic polar protic nature have been subjected to theoretical investigations. The suitability of the molecule for deployment as a modern optical material is examined with positive results. Topological characteristics of the molecule were evaluated using Multiwfn 3.8 to examine electron density distribution and the possible resulting covalent, non-covalent and weak interactions because of such distribution. The potency of the molecule towards brain cancer was evaluated by molecular docking with Auto Dock Tools against two brain cancer protein targets 6ETJ and 6YPE with a good docking score of −6.63 and −6.21 kcal mol−1 respectively and the resulting interactions visualized and its pharmacokinetic properties obtained using online tools.

Effects of a Nutritional Supplement (DìRelaxTM) on Anxiety in Dogs in a Randomized Control Trial Design.

Simple SummaryThe effects of a nutraceutical product, DìRelaxTM, were tested in a cohort of anxious dogs by the C-BARQ questionnaire to assess the presence of problematic behaviors, and by the impossible task paradigm, an experimental procedure to explore dogs’ cognitive performance following an expectancy frustration. Hematological and biochemical analyses showed no adverse effects. The treatment with DìRelaxTM showed a positive effect on the dog’s performances, with some of the behaviors appearing improved. The results suggested that DiRelaxTM may have some ameliorative effect on the cognitive performances of anxious dogs.This study aimed to investigate the efficacy of DìRelaxTM, a nutraceutical formulated to reduce anxiety in dogs, using a randomized controlled trial (RCT) design. The C-BARQ questionnaire, some clinical investigations, and the impossible task test were performed in dogs before and after treatment. The C-BARQ questionnaire is particularly useful for assessing the frequency and severity of problematic behaviors. The impossible task paradigm provides insight into the decision-making processes in the realm of expectancy frustration. Results showed an ameliorative effect on the performances of treated dogs during the solvable phases, with a significant decrease in the time needed to solve the task. No behavioral difference was found between treated and untreated anxious dogs during the unsolvable phase. According to the results from the C-BARQ questionnaire, some of the behaviors appeared to improve. Clinical investigations, including a complete blood cell count and blood chemistry, showed no difference between groups, thus suggesting the safety of the product. In general, this study suggests that DìRelaxTM can be safely administered with no adverse effects and can exercise a beneficial effect on anxious dogs by enhancing their cognitive abilities, but further studies should investigate the best method of administration.

A tetrairon(III) single-molecule magnet and its solvatomorphs: synthesis, crystal structures and vapor-phase processing

With the aim of investigating the impact of lattice solvent on the processability of tetrairon(III) single-molecule magnets by thermal sublimation, two new solvatomorphs of [Fe4(LPh)2(dpm)6] (1) were prepared and structurally characterized along with unsolvated 1 (H3LPh = 2-(hydroxymethyl)-2-phenylpropane-1,3-diol, Hdpm = dipivaloylmethane). All solvatomorphs crystallize in the C2/c space group whereas solvent-free 1 belongs to a different space group (P21/c). The pitch of the propeller-like tetrairon(III) molecules is distinctly different in solvated vs. unsolvated phases, highlighting the effect of intermolecular interactions and crystal packing. The compounds sublime at 450–490 K (in high vacuum conditions, ∼10−6–10−7 mbar) affording thick deposits which display different crystallinity depending on the particular starting material used. However, all sublimed samples retain slow magnetic relaxation with thermal activation parameters comparable to those of microcrystalline 1. The results indicate that factors other than mere molecular structure have a limited influence on the processability of these materials by thermal sublimation.

Who turns to the human? Companion pigs\u2019 and dogs\u2019 behaviour in the unsolvable task paradigm

When facing an unsolvable problem, dogs exhibit spontaneous human-oriented behaviours (e.g. looking at the human partner, gaze alternations between the human and the target) sooner and for longer than domestic cats and hand-raised wolves. These behaviours have been interpreted as interspecific communicative acts aimed to initiate interaction. Here, we compare the emergence of human-oriented behaviours (e.g. orientation towards humans, orientation alternations, vocalizations) in similarly raised family dogs and miniature pigs utilising an unsolvable task paradigm which consists of Baseline (no task), Solvable and Unsolvable phases. Relative to the Baseline phase in which both species showed human-oriented behaviours to a similar extent, during the Unsolvable phase dogs showed more and pigs showed less such behaviours. Species-predispositions in communicative behaviour may explain why dogs have a higher inclination than pigs to initiate interspecific interactions with humans in problem-solving contexts.

Large systems of random linear equations with nonnegative solutions: Characterizing the solvable and the unsolvable phase.

Large systems of linear equations are ubiquitous in science. Quite often, e.g., when considering population dynamics or chemical networks, the solutions must be nonnegative. Recently, it has been shown that large systems of random linear equations exhibit a sharp transition from a phase, where a nonnegative solution exists with probability one, to one where typically no such solution may be found. The critical line separating the two phases was determined by combining Farkas' lemma with the replica method. Here we show that the same methods remain viable to characterize the two phases away from criticality. To this end we analytically determine the residual norm of the system in the unsolvable phase and a suitable measure of robustness of solutions in the solvable one. Our results are in very good agreement with numerical simulations.

Detailed Analysis of Packing Efficiency Allows Rationalization of Solvate Formation Propensity for Selected Structurally Similar Organic Molecules

In structural study of seven bile acids it was identified that their propensity for solvate formation is directly related to the packing efficiency of the unsolvated phases: low packing index, voids, and unsatisfied hydrogen bonding lead to extensive solvate formation, whereas efficient packing leads to the opposite. This was determined to be caused by the presence of OH group attached to carbon C12. Solvate formation was determined to provide a noticeable improvement in the packing efficiency for compounds having ansolvates with inefficient packing.

Solid state forms of 4-aminoquinaldine - From void structures with and without solvent inclusion to close packing.

Polymorphs of 4-aminoquinaldine (4-AQ) have been predicted in silico and experimentally identified and characterised. The two metastable forms, AH (anhydrate) II and AH III, crystallise in the trigonal space group [Formula: see text] and are less densely packed than the thermodynamically most stable phase AH I° (P21/c ). AH II can crystallise and exist both, as a solvent inclusion compound and as an unsolvated phase. The third polymorph, AH III, is exclusively obtained by desolvation of a carbon tetrachloride solvate. Theoretical calculations correctly estimated the experimental 0K stability order, confirmed that AH II can exist without solvents, gave access to the AH III structure, and identified that there exists a subtle balance between close packing and number of hydrogen bonding interactions in the solid state of anhydrous 4-AQ. Furthermore, the prevalence of void space and solvent inclusion in [Formula: see text] structures is discussed.

Algorithm independent bounds on community detection problems and associated transitions in stochastic block model graphs

We derive rigorous bounds for well-defined community structure in complex networks for a stochastic block model (SBM) benchmark. In particular, we analyze the effect of inter-community “noise” (inter-community edges) on any “community detection” algorithm’s ability to correctly group nodes assigned to a planted partition, a problem which has been proven to be NP complete in a standard rendition. Our result does not rely on the use of any one particular algorithm nor on the analysis of the limitations of inference. Rather, we turn the problem on its head and work backwards to examine when, in the first place, well defined structure may exist in SBMs. The method that we introduce here could potentially be applied to other computational problems. The objective of community detection algorithms is to partition a given network into optimally disjoint subgraphs (or communities). Similar to k−SAT and other combinatorial optimization problems, “community detection” exhibits different phases. Networks that lie in the “unsolvable phase” lack well-defined structure and thus have no partition that is meaningful. Solvable systems splinter into two disparate phases: those in the “hard” phase and those in the “easy” phase. As befits its name, within the easy phase, a partition is easy to achieve by known algorithms. When a network lies in the hard phase, it still has an underlying structure yet finding a meaningful partition which can be checked in polynomial time requires an exhaustive computational effort that rapidly increases with the size of the graph. When taken together, (i) the rigorous results that we report here on when graphs have an underlying structure and (ii) recent results concerning the limits of rather general algorithms, suggest bounds on the hard phase.

Solvent Direction of Molecular Architectures in Group 1 Metal Pentacyanocyclopentadienides

AbstractA series of group 1 metal salts of the pentacyanocyclopentadienide anion [Cp(CN)5–] (1) have been crystallised from two distinct solvent systems and the structures of the resulting species investigated by single‐crystal X‐ray diffraction. The structural results show that the bonding mode of 1 and the architecture of the resulting lattice is subtly influenced by the alkali metal and the presence of coordination or lattice solvation. The crystallisation of Na[1] from propan‐2‐ol/n‐pentane produces an open clathrate‐type structure of hexagonal type HS‐I composed of fullerene‐like units in which 1 behaves as a planar five‐fold symmetric node with solvent‐filled lattice voids. In contrast, crystallisation of the sodium, potassium, rubidium and caesium salts from the same solvent system results in highly condensed, unsolvated phases in which 1 adopts a variety of non‐planar coordination modes involving four or five of the CN groups. When crystallised from nitromethane/diethyl ether, the potassium, rubidium and caesium complexes form solvated arrangements with coordinated MeNO2 that contain helical subunits.

Kinetic model of excess activated sludge thermohydrolysis

Thermal hydrolysis of excess activated sludge suspensions was carried at temperatures ranging from 423 K to 523 K and under pressure 0.2–4.0 MPa. Changes of total organic carbon (TOC) concentration in a solid and liquid phase were measured during these studies. At the temperature 423 K, after 2 h of the process, TOC concentration in the reaction mixture decreased by 15–18% of the initial value. At 473 K total organic carbon removal from activated sludge suspension increased to 30%.It was also found that the solubilisation of particulate organic matter strongly depended on the process temperature. At 423 K the transfer of TOC from solid particles into liquid phase after 1 h of the process reached 25% of the initial value, however, at the temperature of 523 K the conversion degree of ‘solid’ TOC attained 50% just after 15 min of the process.In the article a lumped kinetic model of the process of activated sludge thermohydrolysis has been proposed. It was assumed that during heating of the activated sludge suspension to a temperature in the range of 423–523 K two parallel reactions occurred. One, connected with thermal destruction of activated sludge particles, caused solubilisation of organic carbon and an increase of dissolved organic carbon concentration in the liquid phase (hydrolysate). The parallel reaction led to a new kind of unsolvable solid phase, which was further decomposed into gaseous products (CO2). The collected experimental data were used to identify unknown parameters of the model, i.e. activation energies and pre-exponential factors of elementary reactions. The mathematical model of activated sludge thermohydrolysis appropriately describes the kinetics of reactions occurring in the studied system.

Polymorphism and solvatomorphism of bicalutamide

Single crystals of the crystallosolvate [bicalutamide + DMSO] with 1:1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. Polymorphic modifications I and II, the amorphous state, and the DMSO crystallosolvate of bicalutamide were prepared and thermochemistry of fusion processes was studied by DSC technique. The temperature dependence of the saturated vapor pressure of polymorphic form I was obtained and the thermodynamic characteristics of the sublimation process including the crystal lattice energy were calculated. The solution enthalpies of the forms under consideration and the crystallosolvate were acquired by the solution calorimetry procedure. The phase transition enthalpies estimated for form I, form II, and the amorphous state followed the rank order: form I— > form II, form I— > amorphous state, and form II— > amorphous state. The crystal lattice energy of polymorphic form II was determined using the results of sublimation and solution calorimetric experiments. The difference between the crystal lattice energy of the crystallosolvate and unsolvated phases was observed. The dissolution kinetics of forms I, II, the amorphous state, and DMSO solvate in water were investigated.

Phase transitions in random Potts systems and the community detection problem: spin-glass type and dynamic perspectives

Phase transitions in spin-glass type systems and, more recently, in related computational problems have gained broad interest in disparate arenas. In the current work, we focus on the “community detection” problem when cast in terms of a general Potts spin-glass type problem. As such, our results apply to rather broad Potts spin-glass type systems. Community detection describes the general problem of partitioning a complex system involving many elements into optimally decoupled “communities” of such elements. We report on phase transitions between solvable and unsolvable regimes. A solvable region may further split into “easy” and “hard” phases. Spin-glass type phase transitions appear at both low and high temperatures (or noise). Low-temperature transitions correspond to an “order by disorder” type effect wherein fluctuations render the system ordered or solvable. Separate transitions appear at higher temperatures into a disordered (or an unsolvable) phase. Different sorts of randomness lead to disparate behaviors. We illustrate the spin glass character of both transitions and report on memory effects. We further relate Potts type spin systems to mechanical analogs and suggest how chaotic-type behavior in general thermodynamic systems can indeed naturally arise in hard computational problems and spin glasses. The correspondence between the two types of transitions (spin glass and dynamic) is likely to extend across a larger spectrum of spin-glass type systems and hard computational problems. We briefly discuss potential implications of these transitions in complex many-body physical systems.

Polymorphs and solvates of felodipine: analysis of crystal structures and thermodynamic aspects of sublimation and solubility processes

Single crystals of the crystallosolvates [felodipine + N-methylformamide] and [Fel + DMF] with 1 : 1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. The crystal structures were analyzed together with the already published felodipine forms I and II, and crystallosolvate [Fel + formamide]. The temperature dependence of saturated vapor pressure for polymorphic form I was obtained and thermodynamic characteristics of sublimation process with crystal lattice energy estimation were calculated. The fusion processes of solvatomorphs were investigated and their thermophysical parameters were determined. The differences in crystal lattice energy of the three crystallosolvates and those of the unsolvated forms were obtained by solution calorimetry technique. The impact of the “guest”/solvent molecules on the crystal lattice energy of the crystallosolvates was analyzed. The dissolution kinetics of felodipine form I, [Fel + FA], [Fel + N-Me-FA] and [Fel + DMF] in water was investigated. The solution calorimetric and solubility experiments were used to obtain the thermodynamic characteristics of phase transitions (crystallosolvate → unsolvated phase).

Finite-size scaling in randomK-satisfiability problems

We provide a comprehensive view of various phase transitions in random K-satisfiability problems solved by stochastic-local-search algorithms. In particular, we focus on the finite-size scaling (FSS) exponent, which is mathematically important and practically useful in analyzing finite systems. Using the FSS theory of nonequilibrium absorbing phase transitions, we show that the density of unsatisfied clauses clearly indicates the transition from the solvable (absorbing) phase to the unsolvable (active) phase as varying the noise parameter and the density of constraints. Based on the solution clustering (percolation-type) argument, we conjecture two possible values of the FSS exponent, which are confirmed reasonably well in numerical simulations for 2 ≤ K ≤ 3.

Solution-space structure of (some) optimization problems

We study numerically the cluster structure of random ensembles of two NP-hard optimization problems originating in computational complexity, the vertex-cover problem and the number partitioning problem. We use branch-and-bound type algorithms to obtain exact solutions of these problems for moderate system sizes. Using two methods, direct neighborhood-based clustering and hierarchical clustering, we investigate the structure of the solution space. The main result is that the correspondence between solution structure and the phase diagrams of the problems is not unique. Namely, for vertex cover we observe a drastic change of the solution space from large single clusters to multiple nested levels of clusters. In contrast, for the number-partitioning problem, the phase space looks always very simple, similar to a random distribution of the lowest-energy configurations. This holds in the ‘‘easy’’/solvable phase as well as in the ‘‘hard’’/unsolvable phase.

Thermodynamic and Structural Aspects of Hydrated and Unhydrated Phases of 4-Hydroxybenzamide

Single crystals of the anhydrate and hydrate [4-OH-BZA + H2O] with 1:1 stoichiometry of 4-hydroxybenzamide (4-OH-BZA) were grown, and their structures were solved by X-ray diffraction methods. Furthermore, the temperature dependence of the vapor pressure of the anhydrate phase was obtained, and the thermodynamic parameters of sublimation were calculated (ΔGsub° = 58.9 kJ·mol−1; ΔHsub298 = 117.8 ± 0.6 kJ·mol−1; ΔSsub298 = 198 ± 2 J·mol−1·K−1). The differences in crystal lattice energies between the 2:1 and 1:1 hydrates and the anhydrous phase were found to be 2.2 and 6.2 kJ·mol−1, respectively. The absolute values of the crystal lattice energies of the outlined hydrates (ΔHsub298 (2:1) = 120 ± 1 kJ·mol−1; ΔHsub298 (1:1) = 124 ± 1 kJ·mol−1) were obtained on the basis of sublimation and solution calorimetric experiments. Finally, the thermodynamic stability of the three crystalline phases of 4-hydroxybenzamide was estimated. In conclusion, the comparison of the crystal lattice energy of an unsolvated phase with the “stabilization” energy (an energy gain introduced by guest molecules) of the crystal lattice of an solvated phase enables a practical classification of host−guest molecular crystals when the sizes of the host and guest are comparable, thus making it difficult to find out an appropriate qualitative criterion to distinguish them.

A reactivity index study to monitor the role of solvation on the interaction of the chromophores with amino-functional silanol surface for colorimetric sensors

Amino-functional silanol surface are mostly used for the immobilization of inorganic ions, molecules, organic or biochemical molecules onto the mesopore surface. In analytical chemistry, the metal ion uptake was visualized through colorimetric sensors using chromophore molecules. One needs to know the structure–property correlation between the chromophore and silylating agent while choosing chromophore, which is very important to design the sensors. We have used two chromophores representative of hydrophobic and hydrophilic type. We used density functional calculation on all the interacting molecules in both the unsolvated phase and solvated medium within the domain of hard soft acid base principle (HSAB) to look at the localized activity of the interacting atoms of these reacting molecules to formulate a priori rule to choose of the best chromophore. We have as well postulated the mechanism of interaction between chromophore and the silylating agent. The results were compared with experiment and it is observed that solvation plays a detrimental role in the binding of chromophore with silylating agent. The results also show that, the range of reactivity index can be used as a suitable property to scale activity of chromophore molecules suitable for the sensing process. It is observed that the hydrophobic chromophore binds stronger with both the metal and the silylating agent; whereas for the hydrophilic one, it binds only with the silylating agent when solvated and in all cases the metal ion binding is weaker compared to that of the hydrophobic one.

Solvates with anomalous low melting points

Single crystals of the N,N-dimethylformamide (DMF) solvate (1:1) of flurbiprofen (FBP) were grown for the first time and characterised by X-ray diffraction, IR spectrophotometry, DSC and solution calorimetric methods. The structure may be characterised as a layer-structure, where DMF double-sheets are arranged between FBP double-sheets. The FBP and DMF molecules are linked to each other by a hydrogen bond, which is formed between the hydroxyl group of FBP and the carbonyl group of DMF. The conformation of FBP molecules in the DMF solvate differs from analogous enantiomers in the unsolvated form. The differences are discussed from the point of view of the influence of the nature of the solvent on selective crystallisation of the enantiomers. A peculiarity of the solvate is its low melting point, 37.3±0.2°C, with respect to the unsolvated phase, 113.5±0.2°C. Based on solution enthalpies of the solvated and unsolvated phases dissolved in DMF, the difference in crystal lattice energies, 9.8 kJ mol-1, was calculated and the difference in entropies, 33 J mol-1 K-1 estimated. A possible mechanism explaining the low melting point of the solvate is discussed.

Optical spectroscopy of unsolvated and solvated crystalline Alq3

Three novel unsolvated crystalline phases of tris-(8-hydroxyquinoline)-aluminum(III) (Alq3), namely α-, β- and γ-Alq3, have been synthesized and their crystalline structure determined from X-ray diffraction data on powders and single crystals. Both α- and β-Alq3 crystals are triclinic, space group P-1, but differ for the molecular packings. In the γ-Alq3 phase, Alq3 molecules lie about a 3-position of the trigonal P-3 space group. A solvated Alq3(C6H5Cl)1/2 phase (monoclinic, space group P21/n) was also isolated. The optical and vibrational properties of these newly isolated crystal phases of Alq3 have been investigated by absorption, photoluminescence excitation, photoluminescence and Raman spectroscopy. The effect of the different molecular packing on the emission properties has been elucidated, the nature of the photoexcitations clarified, and the vibrational fingerprints of the α- and β-crystalline forms highlighted. The origin of the amorphous nature of the vacuum sublimed thin films is discussed on the basis of the accessibility of many different π–π links between homo- and hetero-chiral Alq3 molecules.

Thermophysical and structural properties of crystalline solvates of tetraphenylporphyrin and their zinc, copper and cadmium metallo-complexes

The results of a thermochemical and structural investigation of the process of desolvation of crystalline solvates of tetraphenylporphyrin H 2TPP with o-, m-xylene; zinc(II) tetraphenylporphyrin ZnTPP with benzene, toluene, o-, m-, p-xylene; cadmium(II) tetraphenylporphyrin CdTPP and copper(II) tetraphenylporphyrin CuTPP with o-, m-xylene are reported. Thermogravimetry and differential scanning calorimetry were used to determine the stoichiometry of crystalline solvates, the energy of activation and the heat effect of the desolvation process. The lattice parameters of the unsolvated crystalline CdTPP, ZnTPP and crystalline solvates of ZnTPP with p-xylene and CuTPP with m-xylene were determined using the X-ray powder diffraction method and the algorithm of Ito. The stoichiometry 1:1 for crystalline solvates [ZnTPP+( p-xylene) 1] and [CuTPP+( m-xylene) 1] was observed. The values of free volume per solvent molecules V free defined as the difference between volume of unit cell of crystalline solvate and the sum of the volume of a unit cell of unsolvated phase of an investigated compound and Van der Waals volume of solvent molecules were calculated. The packing coefficients K chan of the solvent molecules located in channels of the porphyrin matrix were also calculated. For ZnTPP crystalline solvates, we found the correlations between heat of desolvation and free volume per guest molecules of unit cell, as well as between the coefficient of channel packing and the temperature for which the half-lifetime of desolvation phase is equal to 60 min. A linear kinetic compensation effect for the crystalline solvates studied was found.