Crystal Packing Effects Research Articles

Effect of crystal packing and coordinated solvent molecules on metal-ligand bond distances in linear trinuclear nickel compounds with bridging acetato and Schiff base ligands

Abstract A combined experimental and theoretical study on the molecular structure of linear trinuclear nickel compounds of general formula [Ni3(μ-Zsaltn)2(μ-AcO)2(S)2] (Z = H, 1S, and Br, 2S, where S identifies coordinated solvent molecules) is here presented. In these complexes the three metal ions are linked together by bridging acetato ions and tetradentate Schiff base ligands, these last derived from the condensation of 1,3-diaminopropane with two equivalents of 5-Z-salicylaldehyde. Two solvent molecules S can also interact with the terminal nickel ions to complete an octahedral coordination environment. We report the synthesis of [Ni3(μ-Brsaltn)2(μ-AcO)2] (2), and its crystal structure with two coordinated dimethylformamide molecules, [Ni3(μ-Brsaltn)2(μ-AcO)2(DMF)2] (2DMF). Its comparison with the crystal structure of 2 without solvent, together with the series of compounds 1, 1DMF, 1MeOH, 1DMSO, 1Py and 1H2O (MeOH = methanol, DMSO = dimethylsulfoxide, Py = pyridine) available in the literature, allows recognising modification in Ni O and Ni N coordination bond lengths and peculiar intermolecular contacts between neighbour molecules. In order to discern among the contribution of solvent molecules, crystal packing and substituent Z (H or Br) on bond distances (and angles), we performed a systematic theoretical study on four representative derivatives, namely 1, 1DFM, 2 and 2DMF, with the M06 functional and a careful choice of the best basis set. The results indicate that, while the major modulating factor is the presence or absence of the sixth solvent molecule to the peripheral nickel(II) ion, even if less strongly coordinated with Ni O/N bond distances > 2.15 A, π-π stacking interactions and C H⋯π and/or C Br⋯π non-bonded interactions affect the coordination geometry in a significant way.

Puckering behavior in six new phosphoric triamides containing aliphatic six- and seven-membered ring groups and a database survey of analogous ring-containing structures

The influence of a N heteroatom on the ring conformations of six- and seven-membered aliphatic rings in six new C(O)NHP(O)-based phosphoric triamide structures (analysed by X-ray crystallography) is investigated. Additionally the influence of steric and crystal packing effects is also studied by the analysis of Hirshfeld surfaces. The results are compared to analogous structures with three- to seven- aliphatic membered rings deposited in the Cambridge Structural Database. In the newly determined structures, the six-membered rings only show the near-chair conformation with a maximum deviation of the θ puckering parameter of 4.4° from the ideal chair value of 0°/180°, while the seven-membered rings are found in different conformations such as near-chair, twist chair and twist sofa.

Intramolecular London Dispersion Interaction Effects on Gas-Phase and Solid-State Structures of Diamondoid Dimers.

The covalent diamantyl (C28H38) and oxadiamantyl (C26H34O2) dimers are stabilized by London dispersion attractions between the dimer moieties. Their solid-state and gas-phase structures were studied using a multitechnique approach, including single-crystal X-ray diffraction (XRD), gas-phase electron diffraction (GED), a combined GED/microwave (MW) spectroscopy study, and quantum chemical calculations. The inclusion of medium-range electron correlation as well as the London dispersion energy in density functional theory is essential to reproduce the experimental geometries. The conformational dynamics computed for C26H34O2 agree well with solution NMR data and help in the assignment of the gas-phase MW data to individual diastereomers. Both in the solid state and the gas phase the central C-C bond is of similar length for the diamantyl [XRD, 1.642(2) Å; GED, 1.630(5) Å] and the oxadiamantyl dimers [XRD, 1.643(1) Å; GED, 1.632(9) Å; GED+MW, 1.632(5) Å], despite the presence of two oxygen atoms. Out of a larger series of quantum chemical computations, the best match with the experimental reference data is achieved with the PBEh-3c, PBE0-D3, PBE0, B3PW91-D3, and M06-2X approaches. This is the first gas-phase confirmation that the markedly elongated C-C bond is an intrinsic feature of the molecule and that crystal packing effects have only a minor influence.

Torsional Barriers to Rotation and Planarization in Heterocyclic Oligomers of Value in Organic Electronics.

In order to understand the conformational behavior of organic components in organic electronic devices, we have computed the torsional potentials for a library of thiophene-based heterodimers. The accuracy and efficiencies of computational methods for these organic materials were benchmarked for 11 common density functionals with three Pople basis sets against a Focal Point Analysis (FPA) on a model oligothiophene 2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]-thiophene (BTTT) system. This study establishes a set of general trends in regards to conformational preferences, as well as planarization and rotational barriers for a library comprised of common fragments found in organic materials. These gas phase structures are compared to experimental crystal structures to determine the effect of crystal packing on geometry. Finally, we analyze the structure of hole-transporting material DERDTS-TBDT and design a new oligomer likely to be planar in the solid state.

Structural Diversity and Argentophilic Interactions in One-Dimensional Silver-Based Coordination Polymers

A series of new one-dimensional coordination polymer materials, based on Ag(I)–N bond formation, has been synthesized and structurally characterized by single crystal X-ray diffraction. Reactions between the poly-monodentate ligands based on (1E,1′E′)-N,N′-(-bis(1-pyridin-3-yl)methanimine and Ag(I) salts give products that feature simple coordination chains or metallacyclic- and tape-based structures. For the simple chains these are as either isolated units, or assembled in dimeric and tetrameric arrangements through intermetallic, argentophilic interactions. However, crystal packing effects and solvent inclusion are found to readily disrupt this type of bonding. Density functional theory calculations provide an assessment of the bond order and the influence of anion binding on these interactions.

2 H magic-angle spinning NMR and powder diffraction study of deuterated paramagnetic copper(II) glycinato complexes. Information on crystallographic symmetries, stereo-isomerism, and molecular mobility available from ssNMR spectra

Effects of stereochemistry, polymorphism, crystal packing, and solid phase mobility on the 2H magic-angle spinning (MAS) NMR spectra of the paramagnetic Cu(II) glycinato complexes have been investigated. The reliability of information obtained from the spectra, such as symmetry relations within a molecule, number of chemical sites or molecules found in the asymmetric units, was confirmed by previously published X-ray crystal and molecular structures. From the 2H MAS spectra, complemented with powder diffractograms of the synthetized bis(glycinato-d4)copper(II) complexes, we could identify three solid phases, namely the cis aqua and non-aqua forms and the trans non-aqua crystals. A fourth sample was identified as octahedral copper(II) complex chain with bidentate glycine and NO3 ligands in the octahedral building units. Correlations between the sign and magnitude of the observed paramagnetic shifts and the number of bonds and/or the dihedral angles connecting the actual 2H nucleus and the paramagnetic center, useful in structural assignments, were revealed. The agreement of the 2H MAS NMR spectral information with the available crystal diffraction data forecast their applicability in NMR crystallographic works too.

Synthesis, structural and biological studies of two new Co(III) complexes with tridentate hydrazone ligand derived from the antihypertensive drug hydralazine

A new Schiff base derived from the antihypertensive hydralazine (LH) and its Co(III) complexes [CoL2]X*4H2O, where X=NO3− (1) or Cl− (2), were synthesized and characterized using FTIR, UV–Vis, 1H NMR spectroscopy as well as thermal analysis. The crystal structures of the three compounds have been determined using single crystal X-ray diffraction technique. The two complexes structure is strictly divided in a highly ordered part of the [CoL2]+ units and a disordered section containing the anions and sixteen crystal water molecules per unit cell. In the complexes, the two ligand anions (L−) chelate to the Co(III) through the nitrogen atoms in a tridentate meridional manner. The pyridine and phthalazine rings showed deviations from co-planarity in all compounds which attributed to the crystal packing effects as revealed by analysis of their molecular packing using Hirshfeld analysis and further supported by DFT calculations. The optimized structure of the [CoL2]NO3 as a model showed no co-planarity of the two rings while perfectly planar ligand units were predicted in the [CoL2]+ cation indicating that the intermolecular interactions with the nitrate counter anion have a major role in the deviations of the two ring moieties from planarity. The ligand anion (L−) optimized structure using B97D function which include dispersion model showed similar results while the functions (B3LYP and mPW1PW91) which include no dispersion model predicted perfectly planar arrangement. Atoms in molecules (AIM) studies predicted the strength of the Co-N interactions is in the order, Co-N(azomethine)>Co-N(phthalazine)>Co-N(pyridine) which are generally stronger in 2 than 1. The developmental toxicity of LH and its complexes were tested in zebrafish embryos. The ligand itself was very toxic with LC50 of just 2µM as compared to its metal complexes, whereas, at sub-lethal concentration the ligand perturbed the neurogenesis in zebrafish embryos.

Analysis of Biphenyl-Type Inhibitors Targeting the Eg5 α4/α6 Allosteric Pocket.

Eg5 is a mitotic kinesin protein that plays an important role in the formation and maintenance of the bipolar spindle during the mitotic phase. Due to its potentially reduced side effects in cancer therapy, Eg5 is considered to be an attractive target for developing anticancer inhibitors. Herein, we report a computational modeling study involving biphenyl-type inhibitors known to interact with the α4/α6 allosteric pocket of Eg5. Compared to the well-known α2/L5/α3 allosteric inhibitors, biphenyl-type inhibitors show a unique activity profile. In the Eg5–PVZB1194 (a biphenyl-type inhibitor) crystal structure, loop L11, which is located in the entrance of the α4/α6 allosteric-binding pocket, is missing due to crystal-packing effects. To better understand the role of this flexible loop upon biphenyl-type inhibitor-binding, MD simulations were performed to observe the L11 conformations from different states. It was demonstrated that L11 was more stabilized and showed less fluctuation when PVZB1194 was bound to Eg5. Residue Asn287 from L11 forms hydrogen bonding to the sulfone group of PVZB1194, whereby L11 moves inward to the α4/α6 allosteric pocket and moves away from the pocket in absence of the inhibitor. Pharmacophore, three-dimensional (3D)-QSAR, and ADME studies of biphenyl-type inhibitors of Eg5 were also performed. A best pharmacophore model, DDRRH.6, was generated, having correlation coefficients in the 3D-QSAR study of R2 = 0.81 and Q2 = 0.64. Furthermore, docking studies were carried out to observe the interaction between the remaining biphenyl-type inhibitors with Eg5. In addition, on the basis of fragment docking, a structure-based pharmacophore was generated, which shares good overlap of the DHRR features of the pharmacophore model DDHRR.6. The structure-based pharmacophore also contains extra hydrogen-bond acceptors and hydrophobic groups, features which provide possibilities in developing new or improved series of compounds.

Quantum Chemical Dissection of the Shortest P=O⋅⋅⋅I Halogen Bond: The Decisive Role of Crystal Packing Effects.

A supramolecular arrangement comprising a bridged triarylphoshine oxide and an aryl iodide is reported, featuring the shortest ever reported P=O⋅⋅⋅I halogen bond of 2.683(5) Å in the solid state. X-ray crystallographic analysis together with modern quantum chemical methods were enlisted to dissect the individual contributions that compelled this exceptionally short halogen bond, pointing out the decisive role of crystal packing effects.

Modelling micro-crack initiation and propagation of crystal structures with microscopic defects under uni-axial tension by discrete element method

This paper investigates mechanical behaviour and failure process of a 3D notched plate subjected to uni-axial tension using the discrete element method (DEM). The 3D notched plate consisted of different crystal structures, such as simple cubic (SC), body-centered cubic (BCC), face-centered cubic (FCC) and hexagonal close-packed (HCP), where constituent spheres were bonded together by contact bond. The inclination angle of the notch ranged from 0° to 90° with an increment of 15°. The aim of this study is to explore the effects of crystal packing and notch inclination angle on the mechanical responses, crack initiation and propagation, and crack paths. The proposed DEM model was first verified for the pre-cracking behaviour by the corresponding FEM calculation, and was confidently used to study the post-cracking behaviour. Numerical results reveal that the crack initiation and propagation of crystal structures depend on the crystal configuration and notch inclination angle. The loading stiffness of the four crystal structures follows the sequence of HCP>FCC>SC>BCC. The stress concentration factor shows a convex profile against notch inclination angle, with the maximum value at the notch inclination angle of 30° and the minimum value at the notch inclination angle of 90°. The SC and BCC crystal structures show a symmetric feature of crack propagation, whilst the FCC and HCP crystal structures exhibit asymmetric characteristics. In such a loading scenario, the crack initiation and propagation in all the four crystal structures are mainly dominated by the tension failure mode.

Polymorphism of bimolecular crystals of CL-20 with tris[1,2,5]oxadiazolo[3,4-b:3´,4´-d:3″,4″-f]azepine-7-amine

New bimolecular crystals (BMCs) of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) with tris[1,2,5]oxadiazolo[3,4-b:3´,4´-d:3″,4″-f]azepine-7-amine (AZ2) were synthesized. Four different crystal structures — two polymorphic modifications with the CL-20: AZ2 ratio of 1: 1 (BMCs 1 and 2) and two polymorphic modifications with the ratio of 1: 2 (BMCs 3 and 4) — were obtained depending on the crystallization conditions. These crystals were studied by X-ray diffraction. The results of quantum chemical calculations indicate that the new η-conformation found in crystal 1 is not a stable conformer of CL-20 and its existence is attributed to the crystal packing effects in structure 1.

Do All X-ray Structures of Protein-Ligand Complexes Represent Functional States? EPOR, a Case Study

Based on differences between the x-ray crystal structures of ligand-bound and unbound forms, the activation of the erythropoietin receptor (EPOR) was initially proposed to involve a cross-action scissorlike motion. However, the validity of the motions involved in the scissorlike model has been recently challenged. Here, atomistic molecular dynamics simulations are used to examine the structure of the extracellular domain of the EPOR dimer in the presence and absence of erythropoietin and a series of agonistic or antagonistic mimetic peptides free in solution. The simulations suggest that in the absence of crystal packing effects, the EPOR chains in the different dimers adopt very similar conformations with no clear distinction between the agonist and antagonist-bound complexes. This questions whether the available x-ray crystal structures of EPOR truly represent active or inactive conformations. The study demonstrates the difficulty in using such structures to infer a mechanism of action, especially in the case of membrane receptors where just part of the structure has been considered in addition to potential confounding effects that arise from the comparison of structures in a crystal as opposed to a membrane environment. The work highlights the danger of assigning functional significance to small differences between structures of proteins bound to different ligands in a crystal environment without consideration of the effects of the crystal lattice and thermal motion.

Approaching an experimental electron density model of the biologically active trans‐epoxysuccinyl amide group—Substituent effects vs. crystal packing

AbstractThe trans‐epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active ingredients in relation to their biological activity. Here, the synthesis and the electronic properties of the smallest possible active site model compound are reported to close the gap between the unknown experimental electron density of trans‐epoxysuccinyl amides and the well‐known function of related drugs. Intramolecular substituent effects are separated from intermolecular crystal packing effects on the electron density, which allows us to predict the conditions under which an experimental electron density investigation on trans‐epoxysuccinyl amides will be possible. In this context, the special importance of the carboxylic acid function in the model compound for both crystal packing and biological activity is revealed through the novel tool of model energy analysis.

Intermolecular hydrogen bonding H···Cl− in the solid palladium(II)-diaminocarbene complexes

Abstract Weak intermolecular non-covalent H···Cl− interactions in the solid chelated palladium(II)-diaminocarbene complex cis-[PdCl(CNXyl){C(NHXyl)=NHC6H2Me2 NH2}]Cl (3; Xyl=2,6-Me2C6H3) were studied by XRD followed by appropriate DFT calculations. The N–H···Cl contacts for both NH groups in the carbene moiety are different (N1–H···Cl2 3.5258(19), N2–H···Cl2 3.0797(17) Å). The DFT calculations and topological analysis of the electron density distribution within the formalism of Bader’s theory (QTAIM method) were performed for a model cluster of the carbene complex 3. The theoretical data confirmed that the strength of intermolecular HB H···Cl− is different for two NH-protons of the carbene fragment. The influence of crystal packing effects on the formation of hydrogen bonds in the cluster of 3 is noticeable.

Backbone flexibility of extended metal atom chains. Ab initio molecular dynamics for Cr3(dpa)4X2 (X = NCS, CN, NO3) in gas and crystalline phases.

Recently published static DFT and CASSCF/CASPT2 calculations depicted extremely flat Potential Energy Surfaces (PESs) for the Cr-Cr flexibility of Cr3(dpa)4X2 (X = NCS-, CN-, NO3-) extended metal atom chains (EMACs) (M. Spivak, et al., Dalton Trans., 2017, 46, 6202). We herein explore the thermal and crystal packing effects on the structure of EMACs using ab initio molecular dynamics (MD). Car-Parrinello DFT-based simulations of the isolated molecules show that thermal energy favors asymmetric arrangements of the Cr3 chain due, in part, to the bending of the axial ligands (X) and the increased X-Cr distance, both of which weaken X → Cr σ-donation. This effect is even more prominent in the crystalline phase due to the interaction between the axial ligands of neighboring molecules in the unit cell. This could explain the typical discrepancies between the experimental and theoretical characterization of Cr3 EMACs observed in the literature.

A novel angularly fused bistetracene: facile synthesis, crystal packing and single-crystal field effect transistors

Simply “migrating” the aromatic sextet of cata-condensed 2D PAH with the same number of fused benzene rings affords novel organic semiconductors with different properties.

Evidence of crystal packing effects in stabilizing high or low spin states of iron(ii) complexes with functionalized 2,6-bis(pyrazol-1-yl)pyridine ligands.

The molecular structures and magnetic properties of homoleptic iron(ii) compounds [Fe(bpp-COOMe)2](ClO4)2 (1) and [Fe(bpp-triolH3)2](ClO4)2 (2) have been investigated to ascertain their spin crossover (SCO) behaviour. In these hexacoordinated complexes, the bpp (2,6-bis(pyrazol-1-yl)pyridine) ligands adopt a mer-mer coordination mode and carry COOMe or C(O)NHC(CH2OH)3para substituents, respectively, on the central pyridyl ring. In spite of the almost equal donor power of the ligands to the iron(ii) centre, the two compounds feature different spin state configurations at room temperature. Compound 1 displays a highly-distorted octahedral environment around the iron(ii) centre, which adopts a high spin (HS) state at all temperatures, even under an external applied pressure up to 1.0 GPa. By contrast, 2 is characterized by a more regular octahedral coordination around the metal ion and exhibits a low spin (LS) configuration at or below room temperature. However, it shows a thermally-induced SCO behaviour at T > 400 K, along with Light-Induced Excited Spin State Trapping (LIESST) at low temperature, with TLIESST = 38 K. Since DFT (U)M06/6-311+G(d) geometry optimizations in vacuo indicate that both complexes should adopt a HS state and a highly-distorted coordination geometry, the stabilization of a LS configuration in 2 is ultimately ascribed to the effect of intermolecular hydrogen bonds, which align the [Fe(bpp-triolH3)2]2+ cations in 1D chains and impart profound differences in the geometric arrangement of the ligands.

Revisiting antibody modeling assessment for CDR-H3 loop.

The antigen-binding site of antibodies, also known as complementarity-determining region (CDR), has hypervariable sequence properties. In particular, the third CDR loop of the heavy chain, CDR-H3, has such variability in its sequence, length, and conformation that ordinary modeling techniques cannot build a high-quality structure. At Stage 2 of the Second Antibody Modeling Assessment (AMA-II) held in 2013, the model structures of the CDR-H3 loops were submitted by the seven modelers and were critically assessed. After our participation in AMA-II, we rebuilt one of the long CDR-H3 loops with 13 residues (A52 antibody) by a more precise method, using enhanced conformational sampling with the explicit water model, as compared to our previous method employed at AMA-II. The current stable models obtained from the free energy landscape at 300 K include structures similar to the X-ray crystal structures. Those models were not built in our previous work at AMA-II. The current free energy landscape suggested that the CDR-H3 loop structures in the crystal are not stable in solution, but they are stabilized by the crystal packing effect.

Effector Roles of Putidaredoxin on Cytochrome P450cam Conformational States.

In this study, the effector role of Pdx (putidaredoxin) on cytochrome P450cam conformation is refined by attaching two different spin labels, MTSL or BSL (bifunctional spin-label) onto the F or G helices and using DEER (double electron-electron resonance) to measure the distance between labels. Recent EPR and crystallographic studies have observed that oxidized Pdx induces substrate-bound P450cam to change from the closed to the open state. However, this change was not observed by DEER in the reduced Pdx complex with carbon-monoxide-bound P450cam (Fe(2+)CO). In addition, recent NMR studies have failed to observe a change in P450cam conformation upon binding Pdx. Hence, resolving these issues is important for a full understanding the effector role of Pdx. Here we show that oxidized Pdx induces camphor-bound P450cam to shift from the closed to the open conformation when labeled on either the F or G helices with MTSL. BSL at these sites can either narrow the distance distribution widths dramatically or alter the extent of the conformational change. In addition, we report DEER spectra on a mixed oxidation state containing oxidized Pdx and ferrous CO-bound P450cam, showing that P450cam remains closed. This indicates that CO binding to the heme prevents P450cam from opening, overriding the influence exerted by Pdx binding. Finally, we report the open form P450cam crystal structure with substrate bound, which suggests that crystal packing effects may prevent conformational conversion. Using multiple labeling approaches, DEER provides a unique perspective to resolve how the conformation of P450cam depends on Pdx and ligand states.

Effect of packing motifs on the energy ranking and electronic properties of putative crystal structures of tricyano-1,4-dithiino[c]-isothiazole.

We present an analysis of putative structures of tricyano-1,4-dithiino[c]-isothiazole (TCS3), generated within the sixth crystal structure prediction blind test. Typical packing motifs are identified and characterized in terms of distinct patterns of close contacts and regions of electrostatic and dispersion interactions. We find that different dispersion-inclusive density functional theory (DFT) methods systematically favor specific packing motifs, which may affect the outcome of crystal structure prediction efforts. The effect of crystal packing on the electronic and optical properties of TCS3 is investigated using many-body perturbation theory within the GW approximation and the Bethe-Salpeter equation (BSE). We find that a structure with Pna21 symmetry and a bilayer packing motif exhibits intermolecular bonding patterns reminiscent of π-π stacking and has markedly different electronic and optical properties than the experimentally observed P21/n structure with a cyclic dimer motif, including a narrower band gap, enhanced band dispersion and broader optical absorption. The Pna21 bilayer structure is close in energy to the observed structure and may be feasible to grow.