pH-dependent concatenation of an inorganic complex results in solid state helix formation.

Growth of the library of tetraaza macrocyclic pyridinophane ligands is a result of the potential to treat neurodegenerative diseases by binding unregulated redox active metal-ions, scavenging radicals, and reducing oxidative stress. As part of this work, the copper complex of OH PyN 3 Cu (3,6,9,15-tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol) was previously identified as a discrete molecule in the solid state when isolated at lower pH values. However, here we report that OH PyN 3 Cu forms a helical structure upon crystallization around pH 6.5. Several properties of the ligand and complex were evaluated to understand the driving forces that led to the concatenation and formation of this solid-state helix. DFT studies along with a comparison of keto/enol tautomerization stability and bond lengths were used to determine the keto-character of the C=O within each subunit. This pH dependent keto-enol tautomerization is responsible for the solid state intermolecular C=O···Cu bonds observed in this metallohelix (Cu1 H ) when produced around pH 6.5. Perchlorate templating that occurs through hydrogen bonding between perchlorate counter ions and each Cu1 H unit is the primary driving factor for the twist that leads to the helix structure. Cu1 H does not exhibit the typical factors that stabilize the formation of helices, such as intra-strand hydrogen bonding or π-stacking. The helix structure further highlights the diversity of inorganic metallohelices and demonstrates the importance of tautomerization and pH that occurs with the pyridinophane ligand used in this study. To our knowledge and although these phenomenon have been observed individually, this is the first example of a pH dependent keto-enol tautomerization in an azamacrocycle being the driving force for the formation of a metallohelix solid state structure and is a particularly unique observation for pyridinophane complexes.

Sensing of Zn²âº ion by N-furfurylsalicylaldimine based on CHEF process.

The recognition ability of N-Furfurylsalicylaldimine (HL) toward various cations (Pb(2+), Hg(2+), Ba(2+), Cd(2+), Ag(+), Zn(2+), Cu(2+), Ni(2+), Co(2+), K(+), Sr(2+), and Na(+)) has been studied by UV-Vis and fluorescence spectroscopy. The compound showed highly selective fluorescence signaling behaviour for Zn(2+) ions in methanol-water medium based on CHEF process and is capable of distinguishing Zn(2+) from Cd(2+) ion. From single crystal X-ray analysis it is revealed that a Zn(2+) ion binds two ligand molecules through imine nitrogen and phenolate oxygen atom.

Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study.

Pincer type coumarin based N-substituted semicarbazone ligands HL1-4 and their corresponding ruthenium(II) complexes (1-4) were synthesized, analyzed and confirmed by various spectro analytical techniques. The molecular structure of the ligand HL3 and complex 3 was confirmed by single crystal X-ray diffraction analysis. The stoichiometry of complexes 1, 2 and 4 was confirmed by high resolution mass spectroscopy (HRMS). The binding affinity of the compounds with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was established by absorption and emission titration methods. The results of In vitro cytotoxicity showed the significant cytotoxic potential of the complexes against MDA-MB-231 cells (TNBC- Triple-negative breast cancer). Among the complexes, 1 and 4 have shown appreciable results. Further, antimigratory activity against the MDA-MB-231 cells was studied for the complexes 1 and 4. The percentage cell cycle arrest, apoptosis and necrosis were explored by flow cytometry. The in vivo anti-tumor activity of the complexes 1 and 4 using C. elegans as model organism was established by using the tumoral C. elegans strain JK1466 (gld-1(q485)), which bears a mutation in the gld-1 tumor suppressor gene. We have determined the effect of our complexes on tumor gonad reduction and found to be non toxic to the JK1466 worms and they have prolonged their mean lifespan with potential antioxidant ability by overcoming stress responses. Overall, our study reported herein demonstrated that the complexes 1 and 4 could be established as potential metallo-drugs substantiating further exploration.

Bis(2-hydroxy-3-isopropyl-6-methyl-benzaldehyde)ethylenediamine: a novel cation sensor.

Novel substituted phenol-based new symmetrical bis(2-hydroxy-3-isopropyl-6-methyl-benzaldehyde)ethylenediamine (1) has been designed and synthesized. The compound 1 fluorometrically recognized Cu(2+) ion in CH3OH/H2O (90:10, v/v) by exhibiting an increase in emission upon complexation. In addition, Cu(2+) gave rise to a change in colour of the solution of compound 1, which was clearly visible to the naked eye under UV irradiation. The association constant (K) of compound 1 with Cu(2+) ion was computed with the Benesi-Hildebrand plot and Scatchard plot at 43,000 M(-1) and 43,011 M(-1) respectively.

Heparin-Induced Dual Mode Luminescence Modulation of Organic Nanoparticles and Efficient Energy Transfer.

Amphiphilic di-cationic fumaronitrile derivatives with peripheral n-alkyl chains formed organic nanoparticles (NPs) through self-assembly in aqueous media. The NPs exhibited enhanced luminescence in both steady-state and delayed mode in comparison to their molecularly dissolved state. Due to the presence of the multivalent array of positive charges on their surface, they were found to bind heparin, a bio-polyanion which is routinely employed during surgery as an anticoagulant. The electrostatically driven co-assemblies resulted in a significant enhancement in the steady-state and delayed luminescence of the NPs. This provided a highly sensitive detection of the polyanion in aqueous buffer as well as in highly competitive serum and plasma media. Furthermore, and most notably, the heparin based co-assemblies were found to act as efficient donors exhibiting fluorescence resonance energy transfer (FRET) to acceptor dyes with the energy transfer efficiency reaching up to 88%.

Non-stoichiometric carbamazepine cocrystal hydrates of 3,4-/3,5-dihydroxybenzoic acids: coformer-water exchange.

The cocrystallisation of carbamazepine (CBZ) with 3,4-/3,5-dihydroxybenzoic acids (34/35DHBA) with different stoichiometries formed molecular alloys, exchanging a water molecule, in their isostructural CBZ dihydrate form. Furthermore, we show a correlation between the mechanical properties of the CBZ-DHBA cocrystals with the amount of coformer present.

The benefits of Cu Kß radiation for the single-crystal X-ray structure determination of crystalline sponges.

The crystalline sponge method facilitates the X-ray structure determination of samples that do not crystallize or are too sparsely available to afford viable crystallization. By including these materials in a metal-organic framework, the structure of the guest molecules can be determined. Some of the inherent difficulties of this method are discussed and the use of Cu Kß radiation is presented as a simple and effective means to improve the quality of the diffraction data that can be obtained from a sponge crystal.

Refinement of anomalous dispersion correction parameters in single-crystal structure determinations.

Correcting for anomalous dispersion is part of any refinement of an X-ray dif-fraction crystal structure determination. The procedure takes the inelastic scattering in the diffraction experiment into account. This X-ray absorption effect is specific to each chemical compound and is particularly sensitive to radiation energies in the region of the absorption edges of the elements in the compound. Therefore, the widely used tabulated values for these corrections can only be approximations as they are based on calculations for isolated atoms. Features of the unique spatial and electronic environment that are directly related to the anomalous dispersion are ignored, although these can be observed spectroscopically. This significantly affects the fit between the crystallographic model and the measured intensities when the excitation wavelength in an X-ray diffraction experiment is close to an element's absorption edge. Herein, we report on synchrotron multi-wavelength single-crystal X-ray diffraction, as well as X-ray absorption spectroscopy experiments which we performed on the mol-ecular compound Mo(CO)6 at energies around the molybdenum K edge. The dispersive (f') and absorptive (f'') terms of the anomalous dispersion can be refined as independent parameters in the full-matrix least-squares refinement. This procedure has been implemented as a new feature in the well-established OLEX2 software suite. These refined parameters are in good agreement with the independently recorded X-ray absorption spectrum. The resulting crystallographic models show significant improvement compared to those employing tabulated values.

Exploration of Molecular Structure, DFT Calculations, and Antioxidant Activity of a Hydrazone Derivative.

The hydrazine derivatives are known to possess several biological activities including anticancer, antibacterial and anti-fungal, anticonvulsant, and antioxidant. This communication presents the synthesis, X-ray crystal structure analysis, DFT calculations, cell cytotoxicity, and antioxidant activity of the Schiff base 4,4'-((1E,1'E)-hydrazine-1,2-diylidenebis(ethan-1-yl-1-ylidene))bis(benzene-1,3-diol) (compound 2). We have also isolated the side product compound 1 and characterized it using single X-ray crystallography. The crystal structure of compound 1 depicts that the ensuing C-H···N hydrogen bonding interaction is presented and discussed herein. In addition, the calculations using density functional theory (DFT) approximation supported by experimental 1H and 13C NMR studies on the key compound 2 are reported. The results of theoretical and experimental 1H and 13C NMR were concordant. The antioxidant activity of compound 2 was determined by using 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) radical cation assays and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay. Compound 2 demonstrated excellent antioxidant activity in ABTS assay (IC50 = 4.30 ± 0.21 µM) and DPPH assay (IC50 = 81.06 ± 0.72 µM) with almost no cytotoxicity below 25 µM.

Vanishing of the atomic form factor derivatives in non-spherical structural refinement - a key approximation scrutinized in the case of Hirshfeld atom refinement.

When calculating derivatives of structure factors, there is one particular term (the derivatives of the atomic form factors) that will always be zero in the case of tabulated spherical atomic form factors. What happens if the form factors are non-spherical? The assumption that this particular term is very close to zero is generally made in non-spherical refinements (for example, implementations of Hirshfeld atom refinement or transferable aspherical atom models), unless the form factors are refinable parameters (for example multipole modelling). To evaluate this general approximation for one specific method, a numerical differentiation was implemented within the NoSpherA2 framework to calculate the derivatives of the structure factors in a Hirshfeld atom refinement directly as accurately as possible, thus bypassing the approximation altogether. Comparing wR2 factors and atomic parameters, along with their uncertainties from the approximate and numerically differentiating refinements, it turns out that the impact of this approximation on the final crystallographic model is indeed negligible.

Teaching a large-scale crystallography school with Zoom Webinar.

In order to address the loss of crystallographic training opportunities resulting from the cancelation of conventional schools around the world due to the COVID-19 pandemic, we have started an online crystallography school with live lectures and live Q&A using Zoom Webinar. Since we were trying to reach a large audience in a relatively short period, we have limited the school to ten 1 h lectures covering practical aspects of small molecule crystallography including data collection, data processing, and structure solution. In the school, we also covered some advanced topics that students commonly see in their work: absolute structure determination, twinning, and disorder. To round out the education, we provided lectures on macromolecular crystallography and powder diffraction. For students to practice on their own, we used freely available data reduction and structure solution software, as well as datasets with which to practice. To give students credit for course completion, we provided an online exam and an electronic certificate of completion. In this editorial, we will provide some insight into the issues of holding lectures with up to 750 students of very diverse backgrounds and review the efficacy of the school in teaching crystallography for the two cohorts of students.

The C-glycosylation of flavonoids in cereals.

Flavonoids normally accumulate in plants as O-glycosylated derivatives, but several species, including major cereal crops, predominantly synthesize flavone-C-glycosides, which are stable to hydrolysis and are biologically active both in planta and as dietary components. An enzyme (OsCGT) catalyzing the UDP-glucose-dependent C-glucosylation of 2-hydroxyflavanone precursors of flavonoids has been identified and cloned from rice (Oryza sativa ssp. indica), with a similar protein characterized in wheat (Triticum aestivum L.). OsCGT is a 49-kDa family 1 glycosyltransferase related to known O-glucosyltransferases. The recombinant enzyme C-glucosylated 2-hydroxyflavanones but had negligible O-glucosyltransferase activity with flavonoid acceptors. Enzyme chemistry studies suggested that OsCGT preferentially C-glucosylated the dibenzoylmethane tautomers formed in equilibrium with 2-hydroxyflavanones. The resulting 2-hydroxyflavanone-C-glucosides were unstable and spontaneously dehydrated in vitro to yield a mixture of 6C- and 8C-glucosyl derivatives of the respective flavones. In contrast, in planta, only the respective 6C-glucosides accumulated. Consistent with this selectivity in glycosylation product, a dehydratase activity that preferentially converted 2-hydroxyflavanone-C-glucosides to the corresponding flavone-6C-glucosides was identified in both rice and wheat. Our results demonstrate that cereal crops synthesize C-glucosylated flavones through the concerted action of a CGT and dehydratase acting on activated 2-hydroxyflavanones, as an alternative means of generating flavonoid metabolites.

Field-induced slow magnetic relaxation in mixed valence di- and tri-nuclear CoII-CoIII complexes.

Two novel mixed valence CoII-CoIII complexes, namely [CoIICoIII(L1)(ab)(mb)2(H2O)]·dmf (1) and [CoCoII(L2)4(H2O)4]·2H2O (2) [H2L1 = (E)-2-((1-hydroxybutan-2-ylimino)methyl)-6-methoxyphenol, ab = 2-amino-butan-1-ol anion, mb = p-methyl benzoate, H2L2 = 3-((2-hydroxy-3-methoxy-benzylidene)-amino)-propionic acid, and dmf = N,N-dimethyl-formamide], were synthesized and characterized by single crystal X-ray diffraction and magnetic studies at low temperature. The structure determination reveals that both complexes belong to the monoclinic system with P21/c (1) and I2/a (2) space groups. Complex 1 is a dinuclear CoIIICoII compound with distorted octahedral cobalt centers showing different coordination environments. In 2, a bent trinuclear CoCoII complex, the coordination environments around the two terminal CoIII sites are alike, whereas they are different in the central CoII ion. Alternating current/direct current (ac/dc) magnetic studies revealed that both complexes show field-induced slow magnetic relaxation. The dc magnetic susceptibility and magnetization data were analyzed with the following Hamiltonianwhere D and E are the axial and rhombic zero-field splitting (zfs) parameters, respectively, and a good agreement between experimental and simulated results was found using the parameters g⊥ = 2.585, g∥ = 2.437, D = +98.1 cm-1, E/D = 0.008 and F = 8.2× 10-5 for 1 and g⊥ = 2.580, g∥ = 2.580, D = +55.4 cm-1, and E/D = 0.000 for 2.

Accurate crystal structures and chemical properties from NoSpherA2.

The relationship between the structure and the properties of a drug or material is a key concept of chemistry. Knowledge of the three-dimensional structure is considered to be of such importance that almost every report of a new chemical compound is accompanied by an X-ray crystal structure - at least since the 1970s when diffraction equipment became widely available. Crystallographic software of that time was restricted to very limited computing power, and therefore drastic simplifications had to be made. It is these simplifications that make the determination of the correct structure, especially when it comes to hydrogen atoms, virtually impossible. We have devised a robust and fast system where modern chemical structure models replace the old assumptions, leading to correct structures from the model refinement against standard in-house diffraction data using no more than widely available software and desktop computing power. We call this system NoSpherA2 (Non-Spherical Atoms in Olex2). We explain the theoretical background of this technique and demonstrate the far-reaching effects that the improved structure quality that is now routinely available can have on the interpretation of chemical problems exemplified by five selected examples.

Trimerisation of carbon suboxide at a di-titanium centre to form a pyrone ring system.

The reaction of the syn-bimetallic bis(pentalene)dititanium complex Ti2(µ:η5,η5-Pn†)2 (Pn† = C8H4(1,4-SiiPr3)2) 1 with carbon suboxide (O[double bond, length as m-dash]C[double bond, length as m-dash]C[double bond, length as m-dash]C[double bond, length as m-dash]O, C3O2) results in trimerisation of the latter and formation of the structurally characterised complex [{Ti2(µ:η5,η5-Pn†)2}{µ-C9O6}]. The trimeric bridging C9O6 unit in the latter contains a 4-pyrone core, a key feature of both the hexamer and octamer of carbon suboxide which are formed in the body from trace amounts of C3O2 and are, for example, potent inhibitors of Na+/K+-ATP-ase. The mechanism of this reaction has been studied in detail by DFT computational studies, which also suggest that the reaction proceeds via the initial formation of a mono-adduct of 1 with C3O2. Indeed, the carefully controlled reaction of 1 with C3O2 affords [Ti2(µ:η5,η5-Pn†)2 (η2-C3O2)], as the first structurally authenticated complex of carbon suboxide.

Probing the accuracy and precision of Hirshfeld atom refinement with HARt interfaced with Olex2.

Hirshfeld atom refinement (HAR) is a novel X-ray structure refinement technique that employs aspherical atomic scattering factors obtained from stockholder partitioning of a theoretically determined tailor-made static electron density. HAR overcomes many of the known limitations of independent atom modelling (IAM), such as too short element-hydrogen distances, r(X-H), or too large atomic displacement parameters (ADPs). This study probes the accuracy and precision of anisotropic hydrogen and non-hydrogen ADPs and of r(X-H) values obtained from HAR. These quantities are compared and found to agree with those obtained from (i) accurate neutron diffraction data measured at the same temperatures as the X-ray data and (ii) multipole modelling (MM), an established alternative method for interpreting X-ray diffraction data with the help of aspherical atomic scattering factors. Results are presented for three chemically different systems: the aromatic hydro-carbon rubrene (orthorhombic 5,6,11,12-tetra-phenyl-tetracene), a co-crystal of zwitterionic betaine, imidazolium cations and picrate anions (BIPa), and the salt potassium hydrogen oxalate (KHOx). The non-hydrogen HAR-ADPs are as accurate and precise as the MM-ADPs. Both show excellent agreement with the neutron-based values and are superior to IAM-ADPs. The anisotropic hydrogen HAR-ADPs show a somewhat larger deviation from neutron-based values than the hydrogen SHADE-ADPs used in MM. Element-hydrogen bond lengths from HAR are in excellent agreement with those obtained from neutron diffraction experiments, although they are somewhat less precise. The residual density contour maps after HAR show fewer features than those after MM. Calculating the static electron density with the def2-TZVP basis set instead of the simpler def2-SVP one does not improve the refinement results significantly. All HARs were performed within the recently introduced HARt option implemented in the Olex2 program. They are easily launched inside its graphical user interface following a conventional IAM.

The anatomy of a comprehensive constrained, restrained refinement program for the modern computing environment - Olex2 dissected.

This paper describes the mathematical basis for olex2.refine, the new refinement engine which is integrated within the Olex2 program. Precise and clear equations are provided for every computation performed by this engine, including structure factors and their derivatives, constraints, restraints and twinning; a general overview is also given of the different components of the engine and their relation to each other. A framework for adding multiple general constraints with dependencies on common physical parameters is described. Several new restraints on atomic displacement parameters are also presented.

The nature of the counter-anion can determine the rate of water exchange in a metal aqua complex.

The nature of the counter-anion determines the water exchange rate for a series of cationic gadolinium complexes in aqueous solution, as a consequence of the ordering effect that the anion imposes on the structure of the second hydration sphere.

Controlling the variation of axial water exchange rates in macrocyclic lanthanide(III) complexes.

The rate of axial water exchange in well-defined series of lanthanide complexes depends on the extent of second sphere hydration which is determined by complex hydrophobicity and the nature of the lanthanide ion and its counter-ion.

Very bright europium complexes that stain cellular mitochondria.

The synthesis, structure and photophysical properties of a series of highly emissive europium complexes is reported. Certain complexes enter mammalian cells by macropinocytosis and stain the mitochondria selectively, allowing observation of the Eu emission in cellulo by time-gated spectral imaging.