Acta Cryst Research Articles

Construction of Super-Stabilized Direct Electron Transfer Type Glucose Dehydrogenase for Long Term Continuous Glucose Sensing System

Introduction: The development of super-stabilized flavin adenine dinucleotide glucose dehydrogenase (FADGDH) was achieved based on the rational biomolecular engineering.The FADGDH from Burkholderia cepacia (BcGDH) is the ideal enzyme for continuous glucose monitoring (CGM) sensor, because of its inherent DET ability (Yamazaki 2008, Lee 2018). BcGDH is composed of three subunits, which are the catalytic subunit harboring FAD and iron-sulfur (3Fe-4S) cluster, the electron transfer subunit harboring three heme c, and the small subunit which functions as a “hitchhiker” protein. We recently reported the BcGDH catalytic subunit complexed with small subunit (Yoshida et al., 2019, PDB 6a2u), thereby elucidated the intra-molecular electron transfer pathway, and inherent disulfide bond between catalytic subunit and small subunit.BcGDH shows two distinct temperature profiles due to variations in its quaternary structure (Sode 1996, Yamazaki 1999). BcGDH composed of three subunits showed an optimum reaction temperature of approximately 45 ̊C. By increasing temperature, enzyme activity gradually decreases, due to the dissociation of electron transfer subunit. However, at temperature above 60 ̊C, enzyme activity increases again with the increase the temperature and shows second peak at around 70 ̊C, which is derived from the complex composed of catalytic subunit and small subunit. This phenomenon suggested that the dissociation of the electron transfer subunit dominates the stability of BcGDH three subunit complex, which is the essential structure to show DET ability. Namely, to stabilize BcGDH enzyme complex, the stabilization of quaternary structure is the most rational strategy for this enzyme.We recently succeeded in the elucidation of crystal structure of BcGDH complex together with the electron transfer subunit. The availability of quaternary structure of this enzyme enabled us to design inter-subunit disulfide bond in BcGDH. In this study, the designing and characterization of super-stabilized BcGDH is presented. We also characterize the DET ability of the engineered BcGDH, which is the mandatory characteristic of this enzyme for the development of the future innovative biosensing systems. Methods: Amino acid substitution to cysteine residues were carried out at the residues existing on the surface of each subunit, to form inter-subunit disulfide bonds. Recombinantly prepared BcGDH mutant complexes were purified by affinity chromatography. The catalytic activity and thermal stability were investigated. Then DET-type sensors were constructed by immobilization on the gold electrode with self-assembled monolayer (SAM) layer, and investigated their stability by continuous operation. Results and Discussion: Based on the 3D structure of BcGDH complex, disulfide bonds between electron transfer subunit and either catalytic subunit or small subunit were designed. By the screening of the cystaine residue substituted mutants, some mutants showed remarkable high thermal stability as BcGDH complex without the decrease of the catalytic activity. Furthermore, multiple inter-subunit disulfide bonds made the enzyme as super-stabilized which showed high catalytic activity even by the incubation at 70 ̊C. Thus developed engineered enzyme revealed to show DET ability with electrode, indistinguishable to the wild type one. This super-stabilized enzyme will contribute the improvement of the operational stability of enzyme sensors. References Lee et al., Bioelectrochemistry. 121 (2018) 1–6Sode et al., Enzyme Microb. Technol. 19 (1996) 82–85Yamazaki et al., Appl. Biochem. Biotechnol. 77 (1999) 325–336Yamazaki et al., Anal. Lett. 41 (2008) 2363-2373.Yoshida et al., Acta Crystallogr. Sect. D Struct. Biol. 75 (2019) 841–851

Crystal structure and Hirshfeld surface analysis of a third polymorph of 2,6-di-meth-oxy-benzoic acid.

A third crystalline form of the title compound, C9H10O4, crystallizing in the centrosymmetric monoclinic space group P21/c, has been identified during screening for co-crystals. The asymmetric unit comprises a non-planar independent mol-ecule with a synplanar conformation of the OH group. The sterically bulky o-meth-oxy substituents force the carb-oxy group to be twisted away from the plane of the benzene ring by 74.10 (6)°. The carb-oxy group exhibits the acidic H atom disordered over two sites between two O atoms. A similar situation has been found for the second tetra-gonal polymorph reported [Portalone (2011 ▸). Acta Cryst. E67, o3394-o3395], in which mol-ecules with the OH group in a synplanar conformation form dimeric units via strong O-H⋯O hydrogen bonds. In contrast, in the first ortho-rhom-bic form reported [Swaminathan et al. (1976 ▸). Acta Cryst. B32, 1897-1900; Bryan & White (1982 ▸). Acta Cryst. B38, 1014-1016; Portalone (2009 ▸). Acta Cryst. E65, o327-o328], the mol-ecular components do not form conventional dimeric units, as an anti-planar conformation adopted by the OH group favors the association of mol-ecules in chains stabilized by linear O-H⋯O hydrogen bonds.

Fundamental aspects of symmetry and order parameter coupling for martensitic transition sequences in Heusler alloys. Erratum

In the course of further studies of phase transitions in martensites [Driver, Salje, Howard, Lampronti, Ding & Carpenter (2020), Phys. Rev. B, 102, 014105], errors were uncovered in a few entries in Table 3 of the paper by Carpenter & Howard [(2018), Acta Cryst. B74, 560–573]. The required corrections are given here.

Synthesis and Characterization of NLO Material L-Valine L-Valinium Perchlorate Monohydrate for Photonics Applications

L-valine L-valinium perchlorate monohydrate single crystal has been synthesized by slow evaporation technique at room temperature. The crystal structure and space group of the crystal were confirmed by single crystal X-ray diffractometer. Optical behavior of the crystal was analyzed by using UV-visible spectrophotometer. Thermal stability was discussed by using thermo gravimetric analysis. Mechanical strength of the grown crystal was studied using Vickers microhardness tester. Nonlinear optical property was explored to confirm the second harmonic generation efficiency of the grown crystal. These preliminary investigations suggest that the title compound can serve as a potential material for photonics applications. Full Text: PDF ReferencesD. J. Williams, "Nonlinear Optical Properties of Organic and Polymer Materials" (ACS Symposium series 233, American Chemical Society, Washington, DC, 1983). CrossRef K. Bouchouit, Z. Sofiani, B. Derkowska, S. Abed, N. Benali-cherif, M. Bakasse and B. Sahraoui, "Investigation of crystal structure and nonlinear optical properties of 2-methoxyanilinium nitrate", Opt. Commun. 278, 180 (2007), CrossRef K. Bouchouit, H. Bougharraf, B. Derkowska-zielinska, N. Benali-cherif and B. Sahraoui, "Reversible phase transition in semi-organic compound p-Nitroanilinium sulfate detected using second harmonic generation as a tool", Opt.Mater. 48, 215 (2015), CrossRef J. H. Joshi, S. Kalainathan, M. J. Joshi and K. D. Parikh, "Crystal growth, spectroscopic, second and third order nonlinear optical spectroscopic studies of L-phenylalanine doped ammonium dihydrogen phosphate single crystals", Arab. J. Chem. 13, 5018 (2020), CrossRef A. Vijayakumar, A. Ponnuvel and A. Sasikala, "Growth and characterization of α and β form of L-histidine dihydrochloride single crystals", Mater. Today 14, 338 (2019), CrossRef C. Usha, R. Sathakuamri, Lynnette Joseph, D.Sajan, R.Meenakshi, and A.Sinthiya, "Growth and combined experimental and quantum chemical study of glycyl-L-Valine crystal", Heliyon 5, e01574 (2019), CrossRef P. Maadeshwaran and J. Chandrasekaran, "Synthesis, growth and characterization of l-valine cadmium chloride monohydrate—A novel semiorganic nonlinear optical crystal", Optik 122, 1128 (2011) CrossRef S. Pandiyaran, M. Umadevi, R. K. Rajaraman and V. K. Ramakrishnan, "Infrared and Raman spectroscopic studies of l-valine l-valinium perchlorate monohydrate", Spectrochim. Act A Mol. 62, 630 (2005) CrossRef S. Pandiarajan, B. Sridhar and R. K. Rajaram, "L-Valine L-valinium perchlorate monohydrate", Acta Crystallogr. E, 57, 0466 (2001) CrossRef M. Lydia Caroline and S. Vasudevan, "Growth and characterization of l-phenylalanine nitric acid, a new organic nonlinear optical material", Mater. Lett. 63, 41 (2009) CrossRef J. Tauc, R. Grigorovici and A. Vancu, "Optical Properties and Electronic Structure of Amorphous Germanium", Phy. Solid. Stat. 15, 627 (1966), CrossRef J. Tauc, A. Menth and D.L. Wood, "Optical and Magnetic Investigations of the Localized States in Semiconducting Glasses", Phys. Rev. Lett. 25, 749 (1970) CrossRef B. Thirumalaiselvam, R. Kanagadurai, D. Jayaraman and V. Natarajan, "Growth and characterization of 4-methyl benzene sulfonamide single crystals", Opt.Mater. 37, 74 (2014) CrossRef J. Bowman and M. Bevis, "The evaluation of the structure and hardness of processed plastics by the Vickers microhardness test", Colloid Polym. Sci. 255, 954 (1977) CrossRef S. K. Kurtz and T. T. Perry, "A Powder Technique for the Evaluation of Nonlinear Optical Materials", J. Appl. Phy. 39, 3798 (1968) CrossRef M. Prakash, D. Geetha and M. Lydia Caroline, "Crystal growth, structural, optical, spectral and thermal studies of tris(l-phenylalanine)l-phenylalaninium nitrate: A new organic nonlinear optical material", Spectrochim. Act A Mol. 81, 48 (2011) CrossRef

Looking at local classical and quantum forces in stable crystals using multipole-model refined electron densities and orbital-free DFT approximations.

Two distinct approaches, that of energy and that of force, are adopted in quantum mechanics to get insights on chemical processes. In the second one, the net forces acting on the electrons and nuclei in a system (Ehrnefest and Hellmann-Feynman forces, respectively) are determined and a local version of the approach, in terms of force density fields rather than forces, has also been proposed for electrons. This is the path followed by Tsirelson & Stash (2020) in this issue of Acta Crystallographica Section B, to study for the first time the spatial distribution of the electronic forces of different nature acting in stable crystals. Interestingly, by relying on approximations taken from orbital-free DFT, all components of the inner-crystal force can be easily retrieved from multipole-model refined experimental electron densities and their derivatives. No less important is that these calculations are becoming easily doable for any X-ray density crystallographer thanks to a new version of the computer program WinXPRO, purposely developed in the study which is discussed in this commentary.

Crystal structure of aqua-(citric acid)(hydrogen citrato)calcium monohydrate, [Ca(HC6H5O7)(H3C6H5O7)(H2O)]·H2O, from synchrotron X-ray powder data, and DFT-optimized crystal structure of existing calcium hydrogen citrate trihydrate, [Ca(HC6H5O7)(H2O)3].

The crystal structure of 'aquabis-(di-hydrogen citrato)calcium hydrate', better formulated as aqua-(citric acid)(hydrogen citrato)calcium monohydrate, (I), has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. The CaO8 coordination polyhedra are isolated, but occur in layers parallel to the ab plane. Both the Rietveld-refined and DFT-optimized structures indicate that one citrate is doubly ionized and that the other is citric acid. All of the active hydrogen atoms participate in strong (11-16 kcal mol-1) hydrogen bonds. Hydrogen atoms were added to the existing calcium hydrogen citrate trihydrate structure [Sheldrick (1974 ▸). Acta Cryst. B30, 2056-2057; CSD refcode: CAHCIT], (II), and a DFT calculation was carried out to assess the hydrogen bonding and compare it to this optimized structure.

Crystal structures of monohydrate and methanol solvate compounds of {1-[(3,5-bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzyl)amino]cyclopentyl}methanol.

In the title monohydrate compound, 1a, and the methanol solvate compound, 1b, the tri-ethyl-benzene derivative, C35H51N5O, has three functionalized side arms and three ethyl groups, the former being located on one side of the central benzene ring, while the latter are directed to the opposite side. Both the crystals are constructed of structurally similar dimers of 1:1 host-guest complexes held together by N-H⋯O and O-H⋯N hydrogen bonds, and in 1a additionally by O-H⋯O hydrogen bonds. The structure of 1b contains additional highly disordered solvent mol-ecules. Thus, the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] in PLATON was used to generate a modified data set, in which the contribution of the disordered mol-ecules to the structure amplitudes is eliminated. These solvent mol-ecules are not considered in the reported chemical formula.

Bis[tris-(pyridin-2-yl)amine]-iron(II) tris-(di-cyano-methyl-idene)methane-diide.

In the title compound, [Fe{(C5H4N)3N}2][C{C(CN)2}3], both ions lie across centres of inversion, with the anion being statistically disordered over two sets of atomic sites having equal occupancy. The cation and anion have approximate and 32 symmetry, respectively, and the Fe-N bond lengths indicate low-spin FeII. A combination of two-centre C-H⋯N and three-centre C-H⋯(N)2 hydrogen bonds link the ions into complex sheets. Several low-occupancy water mol-ecules are present, whose H atoms could not be located: accordingly, the reflection data were subjected to the SQUEEZE procedure [Spek (2015 ▸). Acta Cryst. C71, 9-18].

Re-refinement of sodium ammonium sulfate dihydrate at 170 K.

The title compound, sodium ammonium sulfate dihydrate (SASD), NaNH4SO4·2H2O, a synthetic analogue of the mineral lecontite, is a well known ferroelectric. The crystal structure of the paraelectric phase has been re-refined at 170 K on the basis of single-crystal X-ray data, improving the previous study [Arzt & Glazer (1994 ▸). Acta Cryst. B50, 425-431] in terms of accuracy regarding hydrogen-atom positions and thus details of the hydrogen bonding. O-H⋯O and N-H⋯O hydrogen bonds between the principal building units [Na(OH2)4O2 octa-hedra, SO4 tetra-hedra and ammonium cations] constitute a three-dimensional network structure.

Bis(μ4-adamantane-1,3-di-carboxyl-ato-1κO 1:2κO 1':3κO 3:4κO 3')octa-carbonyl-1κ2 C,2κ2 C,3κ2 C,4κ2 C-tetra-kis-[tris-(4-methyl-phen-yl)phosphane]-1κP,2κP,3κP,4κP-tetra-osmium(I)(2 Os-Os).

The title complex, [{Os2(CO)4(C21H21P)2}2(C12H14O4)2], is a centrosymmetric mol-ecular loop consisting of two Os-Os sawhorse units linked by two adamantane di-carboxyl-ato bridges. It was synthesized by the microwave-mediated reaction between Os3(CO)12 and adamantane-1,3-di-carb-oxy-lic acid. In contrast to the related complex [{Os2(CO)6}2(μ4-adamantane-1,3-di-acetate)2], the metal-metal axes within each mol-ecule are oriented parallel rather than perpendicular to one another. The crystal structure exhibits cavities that contain residual electron density peaks, but it was not possible to unambiguously identify the solvent therein. The contribution of the disordered solvent mol-ecules to the scattering was removed using the SQUEEZE (Spek (2015 ▸). Acta Cryst. C71, 9-18) routine in PLATON [Spek (2020 ▸). Acta Cryst. E76, 1-11]. These solvent mol-ecules are not considered in the given chemical formula and other crystal data.

Crystal structures of three functionalized chalcones: 4'-di-methyl-amino-3-nitro-chalcone, 3-di-methyl-amino-3'-nitrochalcone and 3'-nitro-chalcone.

The structure of three functionalized chalcones (1,3-di-aryl-prop-2-en-1-ones), containing combinations of nitro and di-methyl-amino functional groups, are presented, namely, 1-[4-(di-methyl-amino)-phen-yl]-3-(3-nitro-phen-yl)prop-2-en-1-one, C17H16N2O3, Gp8m, 3-[3-(di-methyl-amino)-phen-yl]-1-(3-nitro-phen-yl)prop-2-en-1-one, C17H16N2O3, Hm7m and 1-(3-nitro-phen-yl)-3-phenyl-prop-2-en-1-one, C15H11NO3, Hm1-. Each of the mol-ecules contains bonding motifs seen in previously solved crystal structures of functionalized chalcones, adding to the large dataset available for these small organic mol-ecules. The structures of all three of the title compounds contain similar bonding motifs, resulting in two-dimensional planes of mol-ecules formed via C-H⋯O hydrogen-bonding inter-actions involving the nitro- and ketone groups. The structure of Hm1- is very similar to the crystal structure of a previously solved isomer [Jing (2009 ▸). Acta Cryst. E65, o2510].

Crystal structure of bis(5-bromo-1,10-phenanthroline-κ2 N,N')bis-[di-hydro-bis-(pyrazol-1-yl)borato-κ2 N 2,N 2']iron(II) toluene disolvate.

The structure determination of the title compound was undertaken as part of a project on the modification and synthesis of new spin-crossover (SCO) compounds based on octa-hedral FeII bis-(pyrazol-yl)borate complexes. In the course of these investigations, the compound [Fe(C6H8BN4)2(C12H7BrN2)] was synthesized, for which magnetic measurements revealed an incomplete spin-crossover behaviour. Crystallization of this compound from toluene led to the formation of crystals of the toluene disolvate, [Fe(C6H8N4B)2(C12H7N2Br)]·2C7H8. Its asymmetric unit comprises two discrete metal complex mol-ecules and two toluene solvent mol-ecules. One of the latter is severely disordered and its contribution to the diffracted intensities was removed using the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18]. In each complex mol-ecule, the FeII cation is coordinated by the two N atoms of a 5-bromo-1,10-phenanthroline ligand and by two pairs of N atoms of chelating di-hydro-bis(pyrazol-1-yl)borate ligands in the form of a slightly distorted octa-hedron. The discrete complexes are arranged in columns along the a-axis direction with the toluene solvate mol-ecules located between the columns. The 5-bromo-1,10-phenanthroline ligands of neighbouring columns are approximately parallel and are slightly shifted relative to each other, indicating π-π inter-actions.

New Section Editor of Acta Cryst. D

New Section Editor of <i>Acta Cryst. D</i>

Crystal structure and Hirshfeld surface analysis of phen-yl(5,7,8a-triphenyl-1,2,3,7,8,8a-hexa-hydro-imidazo[1,2-a]pyridin-6-yl)methanone with an unknown solvent.

In the title compound, C32H28N2O, the imidazolidine and pyridine rings of the central hexa-hydro-imidazo[1,2-a]pyridine ring system adopt envelope and screw-boat conformations, respectively. The mol-ecule exhibits two weak intra-molecular π-π inter-actions between phenyl rings. In the crystal, mol-ecules are linked via pairs of C-H⋯ O hydrogen bonds, forming inversion dimers. The dimers are further linked by pairs of C-H⋯π inter-actions, forming infinite chains along the c-axis direction. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (73.4%), C⋯H/H⋯C (18.8%) and O⋯H/H⋯O (5.7%) contacts. The contribution of some disordered solvent to the scattering was removed using the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] in PLATON. The solvent contribution was not included in the reported mol-ecular weight and density.

Structural diversity in copper(I) iodide complexes with 6-thioxopiperidin-2-one, piperidine-2,6-di-thione and isoindoline-1,3-di-thione ligands.

Copper(I) iodide complexes are well known for displaying a diverse array of structural features even when only small changes in ligand design are made. This structural diversity is well displayed by five copper(I) iodide compounds reported here with closely related piperidine-2,6-di-thione (SNS), isoindoline-1,3-di-thione (SNS6), and 6-thioxopiperidin-2-one (SNO) ligands: di-μ-iodido-bis-[(aceto-nitrile-κN)(6-sulfanylidenepiperidin-2-one-κS)copper(I)], [Cu2I2(CH3CN)2(C5H7NOS)2] (I), bis-(aceto-nitrile-κN)tetra-μ3-iodido-bis-(6-sulfanylidenepiperidin-2-one-κS)-tetra-hedro-tetra-copper(I), [Cu4I4(CH3CN)4(C5H7NOS)4] (II), catena-poly[[(μ-6-sulfanylidenepiperidin-2-one-κ2 O:S)copper(I)]-μ3-iodido], [CuI(C5H7NOS)] n (III), poly[[(piperidine-2,6-di-thione-κS)copper(I)]-μ3-iodido], [CuI(C5H7NS2)] n (IV), and poly[[(μ-isoindoline-1,3-di-thione-κ2 S:S)copper(I)]-μ3-iodido], [CuI(C8H5NS2)] n (V). Compounds I and II crystallize as discrete dimeric and tetra-meric complexes, whereas III, IV, and V crystallize as polymeric two-dimensional sheets. To the best of our knowledge, compound III is the first instance of an extended hexa-gonal [Cu3I3] structure that is not supported by bridging ligands. Structures I, II, and IV display weak to moderately strong Cu⋯Cu cuprophilic inter-actions [Cu⋯Cu inter-nuclear distances range between 2.5803 (10) and 2.8485 (14) Å]. All structures except III display weak hydrogen-bonding inter-actions between the N-H of the ligand and the μ2 and μ3-I- atoms. Structure III contains classical N-H⋯O inter-actions between the SNO ligands that connect the mol-ecules in a three-dimensional framework. Complex V features π-π stacking inter-actions between the aryl rings of the SNS6 ligands within the same polymeric sheet. In structure IV, there were three partially occupied solvent mol-ecules of di-chloro-methane and one partially occupied mol-ecule of aceto-nitrile present in the asymmetric unit. The SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] was used to correct the diffraction data for diffuse scattering effects and to identify the solvent mol-ecules. The given chemical formula and other crystal data do not take into account the solvent mol-ecules.

Structure refinement of black phosphorus under high pressure.

The structure refinement of black phosphorus was performed at pressures of up to 3.2 GPa at room temperature by powder neutron diffraction techniques. The bond lengths and bond angles between the phosphorus atoms at pressures were precisely determined and confirmed to be consistent with those of the previous single crystal x-ray analysis [A. Brown and S. Rundqvist, Acta Cryst. 19, 684 (1965)]. Although the lattice parameters exhibited an anisotropic compressibility, the covalent P1-P2 and P1-P3 bond lengths were almost independent of pressure and only the P3-P1-P2 bond angle was reduced significantly. On the basis of our results, the significant discrepancy in the bond length reported by Cartz et al. [J. Chem. Phys. 71, 1718 (1979)] has been resolved. Our structural data will contribute to the elucidation of the Dirac semimetal state of black phosphorus under high pressure.

Three new Co-editors appointed to Acta Crystallographica Section D, Structural Biology.

Three new Co-editors appointed to Acta Crystallographica Section D, Structural Biology.

Theoretical study of the properties of X-ray diffraction moiré fringes. III. Theoretical simulation of previous experimental moiré images.

As a practical confirmation of a recently published X-ray moiré-fringe theory [Yoshimura (2015). Acta Cryst. A71, 368-381], computer simulations using this theory were conducted for previous experimental moiré images of a strained bicrystal specimen [Yoshimura (1996). Acta Cryst. A52, 312-325]. Simulated moiré images with a good or fairly good likeness are presented as a result of this simulation, in which the characteristic fringe-and-band and local strain patterns in the experimental images are reproduced well. Experimental moiré images taken when the inclination of the lattice planes was forcedly increased in one of the component crystals of the bicrystal specimen were also fairly well simulated in this computation, and their fringe patterns of inclined fringes are shown to be in accordance with the prediction by the theory. This moiré-fringe theory is thus considered to be widely applicable to the study of moiré images. Furthermore, the successful simulation of the previous experimental moiré images means that a satisfactory theoretical explanation was given for the experimental images, with respect to their characteristic global features. However, this study by the theoretical simulation shows explicitly that some significant peculiarities in the fringe profiles of the experimental images still remain unexplained by this moiré-fringe theory.

Novel phasing method using the origin-free modulus sum function expressed in terms of the absolute electron density.

The origin-free modulus sum function SM refines the set Φ of phases of the structure factors by maximizing the coincidence between the experimental origin-free modulus function and the calculated one in terms of the ρ(Φ)2 density function [Rius, J. (1993). Acta Cryst. A49, 406-409]. Maximization is normally achieved through the recursive application of a Fourier-based algorithm. The purpose of the present study is: (i) to show that ρ(Φ)2 can be replaced by |ρ(Φ)| in SM; (ii) to illustrate the viability of the corresponding phasing algorithm with experimental data.

Charge density of 4-methyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]thiazole-2(3H)-thione. A comprehensive multipole refinement, maximum entropy method and density functional theory study.

The structure of 4-methyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]thiazole-2(3H)-thione (MTTOTHP) was investigated using X-ray diffraction and computational chemistry methods for determining properties of the nitrogen-oxygen bond, which is the least stable entity upon photochemical excitation. Experimentally measured structure factors have been used to determine and characterize charge density via the multipole model (MM) and the maximum entropy method (MEM). Theoretical investigation of the electron density and the electronic structure has been performed in the finite basis set density functional theory (DFT) framework. Quantum Theory of Atoms In Molecules (QTAIM), deformation densities and Laplacians maps have been used to compare theoretical and experimental results. MM experimental results and predictions from theory differ with respect to the sign and/or magnitude of the Laplacian at the N-O bond critical point (BCP), depending on the treatment of n values of the MM radial functions. Such Laplacian differences in the N-O bond case are discussed with respect to a lack of flexibility in the MM radial functions also reported by Rykounov et al. [Acta Cryst. (2011), B67, 425-436]. BCP Hessian eigenvalues show qualitatively matching results between MM and DFT. In addition, the theoretical analysis used domain-averaged fermi holes (DAFH), natural bond orbital (NBO) analysis and localized (LOC) orbitals to characterize the N-O bond as a single σ bond with marginal π character. Hirshfeld atom refinement (HAR) has been employed to compare to the MM refinement results and/or neutron dataset C-H bond lengths and to crystal or single molecule geometry optimizations, including considerations of anisotropy of H atoms. Our findings help to understand properties of molecules like MTTOTHP as progenitors of free oxygen radicals.