Allosteric interactions have been discussed in the context of the acetylcholinesterase (EC 3.1.1.7; AChE) catalysis and inhibition for nearly sixty years, but even determination of more than 200 AChE X-ray structures has not helped to resolve a generally accepted atomic-level mechanism. Allosterism in inhibition of this key enzyme of cholinergic neurotransmission was first proposed by J.-P. Changeux for interaction of AChE with flaxedil and d-tubocurarine in early 1960s. It was followed by meticulous analyses of non-competitive fluorescent ligand binding by P. Taylor group and non-competitive components of reversible and covalent AChE inhibition by W.N. Aldridge and E. Reiner in early 1970s. The accumulated functional evidence of interactions between the active center and spatially remote sites of ligand binding appeared in apparent contradiction with small magnitudes of rarely-observed conformational changes of the 70 kDa catalytic AChE subunit in commonly used cryo- X-ray crystallographic analyses.

We have turned to room-temperature X-ray crystallography to detect conformational diversity of active center human AChE (hAChE) residues reflected in distinct conformations of pyridinium aldoximes found to span active center and allosteric sites of the native and organophosphate (OP) inhibited hAChE. A sequence of conformational changes in the hAChE backbone, triggered by covalent OP inhibition can lead to dissociation of a hAChE homodimer, that we detected by SAXS, and identified structural elements of that allosteric effect. Furthermore, analysis of geometries of crystallographic hAChE homodimers, as well as homodimers of closely related alpha/beta hydrolase-fold proteins provided both evidence and suggestions for structural basis of allosteric interactions in those physiologically important proteins.

This research was supported by the CounterACT Program, National Institutes of Health Office of the Director (NIH OD), and the National Institute of Neurological Disorders and Stroke (NINDS), [Grant Numbers U01 NS083451 and R21 NS098998].

Dimensional reduction, as published by Tulsky and Long in 2001, is “a practical Formalism for Manipulating Solid Structures”.^[1] The introduction of a dimensional reduction agent can reduce the dimensionality of a metal anion framework by several degrees, from a 3D parent compound all the way to a discrete child compound. In our research^[2] we extended the scope of this formalism to metal organic coordination polymers and found similar results.

The use of different types of en-type blocking ligands such as tetramethylethylenediamine (TMEDA), 2,2’-bipyridine (BIPY), 2-(aminomethyl)pyridine (AMPY) and ethylenediamine (EDA) can lead to reduction of the dimensionality of coordination polymers by a degree of one. This effect was observed both for one-dimensional chain polymers, that were reduced to discreet molecular compounds, and for two-dimensional layer structures, that were reduced to one dimensional strands. A reduction by more than one degree of dimensionality could not be observed yet. So far, this dimensional reduction was successfully conducted with Cu(II)aspartate, all stereoisomers of copper(II)tartrate and the copper(II) complex of the tartaric acid derivative dibenzoyl-tartaric acid. The addition of the blocking ligands usually leads to an increase in solubility of the polymer compound, allowing all reactions and crystallisations presented here to be performed in aqueous solutions at room temperature.

[1] E. G. Tulsky and J. R. Long, Chem. Mater. 2001, 13, 1149-1166

[2] M. Kremer, J. v. Leusen and U. Englert, Crystals 2020, 10, 485

The A₀→L1₀ phase transformation, which appears in red gold alloys with compositions close to Au-Cu, is well known as diffusive. However, a shape memory effect has been reported in these alloys, which must involve variant selection during a displacive transformation. Therefore, in this work, the variant selection is studied by EBSD in a polycrystalline red gold alloy heat treated under 4-point bending. For the first time, the L1₀ domains could be identified by EBSD despite their c/a ratio close to unity and their nanometric scale. The orientation relationship between parent and daughter phases was determined and the mechanical work of the variant formation calculated from both the lattice distortion and the experimental orientations. The maximal work criterion, initially introduced for variant selection in martensitic transformations, was applied on large-scale areas with statistical data and it provided quantitative results on the degree of variant selection in both tension and compression.

Halogen bonds recently experienced an increased interest in the crystallographic society due to their high directionality and tunable properties. These properties are a result of the aspherical distribution of the electron density at the halogen atom; the density is shifted perpendicular to the bond forming a ‘sigma hole’. This effect can be investigated with charge density studies based on high resolution diffraction data. Up to now, the focus in those studies was mainly on the halogen atom and its surroundings, whereas the influence of the environment of the halogen bond acceptor has not been investigated in detail yet.

We investigated five crystal structures containing a halogen bond between iodine in a pentafluriodobenzene molecule and nitrogen in four different pyridine derivatives and triethylamine. After a multipole refinement of the diffraction data, the electron density distribution was analyzed according to Bader's Atoms in Molecules theory.

All structures show a polarization of the electron density in the nitrogen molecule towards the halogen direction, but the electron density distribution of the iodine molecule varies widely between the structures. The crystal structures containing pyridine and paraphenyl pyridine express the most pronounced formation of a sigma hole at the iodine atom. The origin of the differences in polarization must be further examined to determine whether it is due to additional interactions of the pentafluoriodobenze with other molecules in the crystal structure or the different structures of the acceptor molecule.

Solitons are localized travelling waves that were first discovered in a shallow canal by Russell in 1834 ¹. They are ubiquitous and exist in various areas of physics, such as nonlinear photonics, magnetic matter, superconductors and cosmology ². However, producing multidimensional solitary states and manipulation of their motion are still large challenges. Liquid Crystals (LCs) are self-organized anisotropic fluids. The coupling between the molecular orientation, the director, and the fluid velocity of LCs introduces a nonlinear term in the director equation of motion, which leads to the possible existence of solitons ³. In this work, we describe the formation of dynamic multidimensional solitons in nematics with negative and positive dielectric anisotropies, respectively. These solitons are self-confined director perturbations that propagate rapidly through the LC bulk and preserve their identities after collisions. We tune the velocity of the solitons by electric fields and control their trajectories through alignment layers. We also show that these solitons can be used as vehicles for 2D delivery of micro-cargos.

1 Dauxois, T. & Peyrard, M. Physics of solitons, (Cambridge University Press, 2006).

2 Kartashov, Y. V., Astrakharchik, G. E., Malomed, B. A. & Torner, L., Nature Reviews Physics, 1, 185-197 (2019).

3 Lam, L. & Prost, J. Solitons in liquid crystals, (Springer Science & Business Media, 2012).

In this communication we will present a data reduction software for single crystal neutron diffraction, named Int3D. This software has been initially developed to perform the data reduction for the D19 instrument of the Institut Laue Langevin (ILL), a large solid angle single crystal neutron diffractometer. However, it has been designed to be easily extended to any diffractometer operating with a 2D detector, and it will be adapted as well to the D9 and D10 single crystal diffractometers of the ILL in the near future.

Int3D consists of a graphical user interface (GUI) through which the users can visualise, interact with and process their raw data to obtain the integrated intensities of the reflections collected during the diffraction experiment. It allows to perform all the required tasks of the data reduction process: the peak search, the determination of the orientation matrix, the integration of the reflection intensity and the refinement of the cell and instrument parameters.

The application is written in PyQt. The visualization tools are based on Silx [1] and VTK [2] libraries. This allows fast and efficient 2D and 3D data visualization, which is extremely useful to validate the different steps in the data reduction process. On the other hand, all the crystallographic calculations are based on the CrysFML library [3], a crystallographic library written in Fortran. Forpy [4] is used to pass data at runtime between the GUI and the Fortran programs running in the background, coupling the visualization with the crystallographic calculations.

A demonstration of a full data reduction process carried out with Int3D can be found here [5].

References:

[1] https://www.silx.org/

[2] https://vtk.org/

[3] https://code.ill.fr/scientific-software/crysfml

[4] https://github.com/ylikx/forpy

[5] https://youtu.be/dOxVcku10dM

An ambient conditions alpha polymorph of solid AgF₂ with a layered Ag^IIF₂ structure recently received attention due to numerous structural and electronic similarities with oxocuprate precursors of high-temperature superconductors [1]. The individual [Ag^IIF₂] layers here are isoelectronic with undoped [CuO₂] sheets in oxocuprates and both systems are antiferromagnetic semiconductors with charge-transfer band gap. Interestingly, diamagnetic mixed-valence Ag^IAg^IIIF₄ beta polymorph was also reported [2]. Notably, β form undergoes a rapid exothermic conversion to the α form (Ag^IAg^IIIF₄ à 2Ag^IIF₂) when the temperature is raised to 0 °C. This observation is important, since a direct relation between the disproportionation reaction and unconventional superconductivity is well documented for charge-ordered insulator BaBi^3+/5+O₃; this compound can be converted to superconductor by a non-isovalent substitution leading to Ba_1-xK_xBiO₃ [3]. In order to better understand the thermodynamics and electron-lattice interplay in the two AgF₂ phases, we have calculated their lattice vibrations and related electronic structures using various Density Functional Theory exchange-correlation functionals and we have evaluated phonons in quasi-harmonic approximation. Additionally, we have evaluated anharmonicity effects in lattice dynamics of the alpha phase by applying a new developed method based on a nonperturbative approach of probing the crystals potential-energy landscape in the multidimensional space of atomic displacements [4]. This permitted us to calculate the alpha-beta (p,T) phase diagram. Importantly, for alpha-Ag^IIF₂ we have identified Ag-F bond stretching modes of B_2g symmetry which induce modulated intervalence charge transfer (charge density wave) with unusually strong response to on-site Coulombic correlation [5].

Acknowledgment: K.T. and M.D. acknowledges the ERDF, Research and Innovation Operational Programme, for project No. ITMS2014+: 313011W085; the Slovak Research and Development Agency, grant No. APVV-18-0168 and Scientific Grant Agency of the Slovak Republic, grant No. VG 1/0223/19. WG acknowledges Polish National Science Center for Maestro grant (UMO-2017/26/A/ST5/00570). The calculations were carries out using Aurel supercomputing facility in CC of Slovak Academy of Sciences acquired in projects ITMS 26230120002 and 26210120002 funded by ERDF and the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw under grant no. ADVANCE++ (GA76-19).

References:

[1] J. Gawraczyński, D. Kurzydłowski, W. Gadomski, Z. Mazej, T. Jaroń, A. Ozarowski, S. Hill, P. J. Leszczyński, K. Tokár, M. Derzsi, P. Barone, K. Wohlfeld, J. Lorenzana and W. Grochala, Proc. Natl. Acad. Sci. USA, 116, 1495 (2019).

[2] C. Shen, B, Žemva, G. M. Lucier, O. Graudejus, J. A. Allman, N. Bartlett, Inorg. Chem., 38, 4570 (1999).

[3] C. Franchini, G. Kresse, and R. Podloucky, Phys. Rev. Lett. 102, 256402 (2009).

[4] K. Parlinski, Phys. Rev. B, 98, 054305 (2018).

[5] K. Tokár, M. Derzsi, W. Grochala, arXiv:2008.03081 (2020).

Palladium is an important catalyst in many catalytic reactions with diversity of technological applications. Apart from the pure metal, catalytic activity is being increasingly attributed also to palladium oxides, which however remain poorly characterized. The only thoroughly scientifically studied and technologically exploited palladium oxide is PdO. In our present study we focus on theoretical examination of PdO₂. Its formation was observed under elevated hydrostatic pressure and rutile structure was proposed [1,2]. Using Density Functional Theory modelling, we have obtained more detailed information about existence of PdO₂ including possible polymorphs with distinct oxygen anions (O^2-, (O₂)^2-), details of crystal structures, vibrational properties and thermodynamic stability [3]. Here we will show that apart from the rutile structure, PdO₂ can form in variety of polymorphs with much more favorable formation enthalpies. We examine these polymorphs in relation to PtO₂ and calculate their IR/Raman fingerprints in broader pressure range that can help to identify them in future experiments.

Acknowledgement: The European Regional Development Fund, Research and Innovation Operational Programme, for project No. ITMS2014+: 313011W085; Scientific Grant Agency of the Slovak Republic, grant No. VG 1/0223/19; the Slovak Research and Development Agency, grant No. APVV-18-0168; Aurel supercomputing infrastructure in CC of Slovak Academy of Sciences acquired in projects ITMS 26230120002 and 26210120002 funded by ERDF.

References:

[1] I. S. Shaplygin, G. L. Aparnikov, V. B.Lazarev, Zhurnal Neorganicheskoi Khimii, 23, 884 (1978).

[2] G. I. Goncharenko, V. B. Lazarev, I. S. Shaplygin, Zhurnal Neorganicheskoi Khimii, 30, 3032 (1985).

[3] D. Fabušová, Bachelor thesis 2020, available at https://opac.crzp.sk/

The design and synthesis of pharmaceutical co-crystals have received great interest in recent years. co-crystallization of drug substances offer a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hygroscopicity, dissolution rates, and bioavailability. This short review summarizes this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of co-crystals, co-crystal preparation, and characterization, comparison of different (traditional and novel) methods for co-crystal formation, and implications for regulatory control and intellectual property protection. Traditionally, co-crystal can be prepared by solvent evaporation method, grinding, and slurry method, but, every method has limitations for certain conditions. The current trend for co-crystal formation uses sophisticated methods such as the hot-melt extru­sion method, spray drying method, supercritical fluid technology, and the newest, and laser irradiation method. The development of new method is not only to overcome the limitation of traditional co-crystallization methods but also to generate a simpler step and continuous process for the production of co-crystal products. This article gives a brief explanation of each method that can be used to generate pharmaceutical co-crystals.

Silver chloride, AgCl, is well known crystalline solid that has been mostly recognized due to its photoactive properties. Intriguingly, no other crystallize phase of silver with chlorine is known. This is quite surprising considering the richness of stoichiometries in other transition metal halides, the most frequent being di- and trichlorides. Additionally, Cu and Au that sits together with Ag in Group 11 form apart from mono- and dihalides also M₄Cl₈ and M₂Cl₆ phases. The lack of these crystalline phases in the Ag-Cl system is even more surprising since the binary system of silver fluorides is quite rich [1]. The absence of their chloride counterparts may indicate incompatibility of chlorine with higher oxidation states of silver, but this issue requires through examination. Employing evolutionary algorithms (EA) in combination with Density Functional Theory (DFT), we have recently uncovered chemical identity of metastable crystalline AgCl₂ phase [2]. Subsequently, computing simple DFT models of Cl-staffed/enriched cubic silver and vice versa, we have demonstrated possible existence of several other stoichiometries [3,4]. In this contribution we present their crystal and electronic structures and formation enthalpies as predicted by combined EA+DFT approach, while considering also the existence of chlorine substituted Ag_xF_y phases and possibility to stabilize them under external pressure. Our ongoing exhaustive computational study reveals very different crystal chemistry of silver chlorides in respect to fluorides involving polychloride anions.

Acknowledgement: The European Regional Development Fund, Research and Innovation Operational Programme, for project No. ITMS2014+: 313011W085; Scientific Grant Agency of the Slovak Republic, grant No. VG 1/0223/19; the Slovak Research and Development Agency, grant No. APVV-18-0168; Aurel supercomputing infrastructure in CC of Slovak Academy of Sciences acquired in projects ITMS 26230120002 and 26210120002 funded by ERDF.

References:

[1] T. Nakajima, B. Žemva and A. Tressaud (Editors), Elsevier Science S.A, (2000).

[2] M. Derzsi A. Grzelak, P. Kondratiuk, K.Tokár and W. Grochala, Crystals, 9, 423 (2019).

[3] M. Uhliar, Bachelor thesis 2019, available at https://opac.crzp.sk/ .

[4] M. Uhliar and M. Derzsi, 19^th Symposium on fluorine chemistry, Warsaw (2019).