Crystal Packing Interactions Research Articles

Enhancement with Hirshfeld surface analysis of structural, electrical, dielectric and luminescent performance of two bioactive V-substituted polytungstates

Two new V-substituted polytungstates of piperazinium derivatives, (H2pip)2[V2W4O19]·4H2O (1) and (H2pipEtOH)2[V2W4O19]·4H2O (2), (H2pip = piperazin-1,4-dium; H2pipEtOH = 1-ethylhydroxy-piperazin-1,4-dium), were synthesized in aqueous solution and characterized by ICP and elemental analysis, X-ray diffraction, IR, Raman, UV–Visible, luminescence, DSC and conductivity measurements. X-ray structural and Hirshfeld surface analysis of 1 and 2 with fingerprint plots evidenced polymeric-3D-hydrogen bonded networks of porous extended polyanionic frameworks filled by H2pip and H2pipEtOH dications. Inspection of intermolecular interactions in crystal packing of 1 and 2, via Hirshfeld surface analysis reveals that about two-thirds of the close contacts are associated with O⋯H/H⋯O intermolecular interactions. The conductivity and dielectric behavior of both compounds have been studied as a function of temperature and frequency. The electrical analysis shows that the Nyquist plots (Z″ versus Z′) are well fitted to an equivalent circuit model which consists of a parallel combination of a bulk resistance R and constant phase elements CPE. Besides, the dielectric constants ε′, ε″ and loss tangent (tan(δ)) versus frequency, at several temperatures, show a distribution of relaxation times. Furthermore, the activation energy responsible for relaxation has been evaluated and found to be close to the conductivity. Moreover, the biological properties of both compounds were investigated showing promising antibacterial and antifungal activities.

Easy mammalian expression and crystallography of maltose-binding protein-fused human proteins.

We present a strategy to obtain milligrams of highly post-translationally modified eukaryotic proteins, transiently expressed in mammalian cells as rigid or cleavable fusions with a mammalianized version of bacterial maltose-binding protein (mMBP). This variant was engineered to combine mutations that enhance MBP solubility and affinity purification, as well as provide crystal-packing interactions for increased crystallizability. Using this cell type-independent approach, we could increase the expression of secreted and intracellular human proteins up to 200-fold. By molecular replacement with MBP, we readily determined five novel high-resolution structures of rigid fusions of targets that otherwise defied crystallization.

Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6-di(CH2OH)py)2]NO3.

Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44–28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis.

A theoretical study of the electronic structure and charge transport properties of thieno[2,3-b]benzothiophene based derivatives.

The electronic structure and charge transport properties of thieno[2,3-b]benzothiophene (TBT) and its eight derivatives are investigated via density functional theory (DFT). The impact of different π-bridge spacers (1, the dimer of TBT; 2, vinyl; 3, phenyl; and 4, tetrafluorophenyl) and substituents (5, phenyl; 6, biphenyl; 7, naphthalenyl; and 8, benzothiophenyl) on the geometric structures, reorganization energy, absorption spectra, frontier orbitals, ionization potentials (IPs) and electron affinities (EAs) of all the compounds is explored to establish the relationship between the structure and properties. All the compounds show wide band gaps and low-lying HOMOs, and the IPs of all the TBT derivatives are higher than that of pentacene. The crystal packing interactions, transfer integrals and charge carrier mobilities of compounds 1, 2, 4 and 6 are also calculated. The calculated results demonstrated that these kinds of materials may exhibit good environmental stability and high charge mobility due to their large conjugated planar structure, close π-stacking arrangement, and multiple intermolecular interactions. For compounds 1 and 4, the predicted hole mobility is as high as 0.28 and 0.17 cm(2) V(-1) s(-1), respectively, indicating that both of them benefit hole transport, while compounds 2 and 6 exhibit balanced charge transport properties with the hole and electron mobilities of 0.012 and 0.013 cm(2) V(-1) s(-1), respectively, for compound 2. Compound 6 shows a relatively lower charge mobilities of 10(-3) order of magnitude for both holes and electrons due to the larger reorganization energy and lower transfer integrals.

Cocrystals of isoliquiritigenin with enhanced pharmacokinetic performance

Isoliquiritigenin (ISL) is an abundant dietary flavonoid with numerous pharmacological activities. However, isoliquiritigenin is poorly absorbed by the body which limits its clinical usage. Cocrystallization has attracted attention recently as a means of modifying unfavourable physicochemical properties of compounds. Herein, we report the synthesis of two new cocrystals of ISL: isoliquiritigenin–nicotinamide (ISL–NIC) and isoliquiritigenin–isonicotinamide (ISL–INM). To our knowledge, this is the first report of flavonoid cocrystals from a compound with a chalcone structure. The cocrystals are characterized by various techniques, including powder X-ray diffraction, Raman spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Through single-crystal X-ray diffraction analysis, we investigate the crystal packing and intermolecular interactions of ISL cocrystals. The binary phase diagrams of ISL and the conformers are constructed for understanding the thermal behaviors of physical mixtures upon heating. Pharmacokinetic studies show that both of the ISL cocrystals outperform the pure form of ISL and its monohydrate with increases in bioavailabilities.

New crystal form of human ubiquitin in the presence of magnesium

Ubiquitin is a small globular protein that has a considerable number of lysine residues on its surface. This results in a high surface entropy that precludes the formation of crystal-packing interactions. To date, only a few structures of the native form of ubiquitin have been solved, and most of the crystals that led to these structures were obtained in the presence of different divalent metal cations. In this work, a new crystallographic structure of human ubiquitin solved from crystals grown in the presence of magnesium is presented. The crystals belonged to a triclinic space group, with unit-cell parameters a = 29.96, b=30.18, c = 41.41 Å, α = 88.52, β = 79.12, γ = 67.37°. The crystal lattice is composed of stacked layers of human ubiquitin molecules with a large hydrophobic interface and a smaller polar interface in which the magnesium ion lies at the junction between adjacent layers in the crystal. The metal ion appears in a hexa-aquo coordination, which is key to facilitating the crystallization of the protein.

Sent packing: protein engineering generates a new crystal form of Pseudomonas aeruginosa DsbA1 with increased catalytic surface accessibility.

Pseudomonas aeruginosa is an opportunistic human pathogen for which new antimicrobial drug options are urgently sought. P. aeruginosa disulfide-bond protein A1 (PaDsbA1) plays a pivotal role in catalyzing the oxidative folding of multiple virulence proteins and as such holds great promise as a drug target. As part of a fragment-based lead discovery approach to PaDsbA1 inhibitor development, the identification of a crystal form of PaDsbA1 that was more suitable for fragment-soaking experiments was sought. A previously identified crystallization condition for this protein was unsuitable, as in this crystal form of PaDsbA1 the active-site surface loops are engaged in the crystal packing, occluding access to the target site. A single residue involved in crystal-packing interactions was substituted with an amino acid commonly found at this position in closely related enzymes, and this variant was successfully used to generate a new crystal form of PaDsbA1 in which the active-site surface is more accessible for soaking experiments. The PaDsbA1 variant displays identical redox character and in vitro activity to wild-type PaDsbA1 and is structurally highly similar. Two crystal structures of the PaDsbA1 variant were determined in complex with small molecules bound to the protein active site. These small molecules (MES, glycerol and ethylene glycol) were derived from the crystallization or cryoprotectant solutions and provide a proof of principle that the reported crystal form will be amenable to co-crystallization and soaking with small molecules designed to target the protein active-site surface.

Structural considerations on acridine/acridinium derivatives: Synthesis, crystal structure, Hirshfeld surface analysis and computational studies

This article describes a detailed study of the molecular packing and intermolecular interactions in crystals of four derivatives of acridine, i.e. 9-methyl-, 9-ethyl, 9-bromomethyl- and 9-piperidineacridine (1, 2, 3 and 4, respectively) and three 10-methylacridinium salts containing the trifluoromethanesulphonate anion and 9-vinyl-, 9-bromomethyl, and 9-phenyl-10-methylacridinium cations (5, 6 and 7, respectively). The crystal structures of all of the compounds are stabilized by long-range electrostatic interactions, as well as by a network of short-range C–H⋅⋅⋅O (in hydrates and salts 3 and 5–7, respectively), C–H⋅⋅⋅π, π–π, C–F⋅⋅⋅π and S–O⋅⋅⋅π (in salts 5–7) interactions. Hirshfeld surface analysis shows that various intermolecular contacts play an important role in the crystal packing, graphically exhibiting the differences in spatial arrangements of the acridine/acridinium derivatives under scrutiny here. Additionally, computational methods have been used to compare the intermolecular interactions in the crystal structures of the investigated compounds. Computations have confirmed the great contribution of dispersive interactions for crystal lattice stability in the case of 9-substituted acridine and electrostatic interactions for the crystal lattice stability in the case of 9-substituted 10-methylacridinium trifluoromethanesulphonates. The value of crystal lattice energy and the electrostatic contribution in the crystal lattice energy of monohydrated acridine derivatives have confirmed that these compounds have behave as acridinium derivatives.

Role of Crystal Packing and Weak Intermolecular Interactions in the Solid State Fluorescence of N-Methylpyrazoline Derivatives

Six compounds containing an N-methylpyrazoline ring fused with flavanone derivatives have been synthesized and characterized by X-ray structural studies and fluorescence spectroscopy. The influence of molecular arrangement on the emission properties, including fluorescence lifetime and quantum yield, was discussed on the basis of structural data and detailed analysis of the Hirshfeld surfaces. The correlation of fluorescence and crystal packing reveals that solid state emission of this class of compounds strongly depends on intermolecular interactions present in a different crystal lattice. It was observed that the inverse of fluorescence lifetime (1/τavg) is dependent on a percentage contribution of H···O and H···N contacts in the Hirshfeld surface. In addition, the lipophilicity (log P) of these compounds is related to contribution of C···H interactions as well as noncovalent bonding involving a halogen atom.

Studying the Role of C═O···C═O, C═O···N–O, and N–O···N–O Dipole–Dipole Interactions in the Crystal Packing of 4-Nitrobenzoic Acid and 3,3′-Dinitrobenzophenone Polymorphs: An Experimental Charge Density Study

An experimental charge density study of 4-nitrobenzoic acid and 3,3′-dinitrobenzophenone polymorphs has been performed to study the role played by various intermolecular interactions in the crystal packing. The study highlights the importance of dipole–dipole interactions analyzed with the help of Bader’s quantum theory of atoms in molecules (QTAIM), low-reduced density gradient (RDG) based topological descriptors of electron density and computations. The molecular pairs held by antiparallel C═O···C═O, C═O···N–O, and N–O···N–O type dipole–dipole interactions were found to contribute significantly toward stability especially in the case of 3,3′-dinitrobenzophenone, Form II. The low-RDG based descriptors were used for understanding the nature of these dipole–dipole interactions, which indicates the involvement of multiple atoms in stabilizing many of these interactions. The significant contributions from the O···C, O···O, and O···N contacts arising from these dipole–dipole interactions in crystal packing are also revealed from the Hirshfeld surface analysis of these crystals.

New water soluble heterometallic complex showing unpredicted coordination modes of EDTA

A mesoporous 3D polymeric complex (I) having formula {[Zr(IV)O-μ3-(EDTA)Fe(III)OH]·H2O}n has been crystallized and characterized by various techniques. Single-crystal X-ray diffraction analysis revealed that complex (I) crystallized in chiral monoclinic space group Cc (space group no. 9) with unexpected coordination modes of EDTA and mixture of two transition metal ions. In this complex, the coordination number of Zr(IV) ion is seven where four carboxylate oxygen atoms, two nitrogen atoms, one oxide atom are coordinating with Zr(IV). Fe(III) is four coordinated and its coordination environment is composed of three different carboxylic oxygen atoms from three different EDTA and one oxygen atom of –OH group. The structure consists of 4-c and 16-c (2-nodal) net with new topology and point symbol for net is (336·454·530)·(36). TGA study and XRPD pattern showed that the coordination polymer is quite stable even after losing water molecule and –OH ion. Quenching behavior in fluorescence of ligand is observed by complexation with transition metal ions is due to n–π⁎ transition. The SEM micrograph shows the morphology of complex (I) exhibits spherical shape with size ranging from 50 to 280nm. The minimum N2 (SBET=8.7693m2/g) and a maximum amount of H2 (high surface area=1044.86m2/g (STP)) could be adsorbed at 77K. From DLS study, zeta potential is calculated i.e. −7.94 shows the negative charges on the surface of complex. Hirshfeld surface analysis and fingerprint plots revealed influence of weak or non bonding interactions in crystal packing of complex.

Crystal Structure Optimization and Semi-Empirical Quantum Chemical Calculations of Fused Bicyclic Heterocycles

The crystal structures of two fused pyridine derivatives viz Ethyl 3-amino-6-phenyl-4-tolylfuro[2,3-b]pyridine-2-carboxylate (I) and Ethyl 3-amino-6-phenyl-4-tolylthieno[2,3-b] pyridine-2-carboxylate (II) were optimized by semi-empirical methods using MOPAC2009 program. The geometries optimized for both the structures from Austin Model 1 (AM1) and Parametrization Model 6 (PM6) describe the conformational discrepancy and crystal packing effects. The parametric molecular electrostatic potential (PMEP) calculated by AM1 semi-empirical method describe the involvement of nitrogen and oxygen atoms in the crystal packing interactions in both the structures. The frontier molecular orbitals highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) indicate the intramolecular charge transfer interactions. The HOMED indices computed for the phenyl rings in the structures describe the p-electron delocalization. The linear regression analysis shows good correlation between experimental and theoretical structures.

Two isostructural halogen derivatives of 9-ethylcarbazole: crystal structure, Hirshfeld surface analysis, and structural comparison with other simple analogs

This article describes a detailed study of the molecular packing and intermolecular interactions in crystals of two derivatives of 9-ethylcarbazole, i.e., 3-chloro- and 3-bromo-9-ethylcarbazole (1 and 2, respectively). A significance of this study lies both in the comparison drawn between the crystal structures of these compounds and those of several of their simple analogs [i.e., 3,6-dibromo-9-ethylcarbazole (3), 3,6-dibromo-9-methylcarbazole (4), 3,6-dibromocarbazole (5), 3-bromocarbazole (6), 3,6-diiodocarbazole (7), 9-ethylcarbazole (8), 9-methylcarbazole (9) and carbazole (10)], and in the preliminary assessment of their suitability as active materials for organic electronics. This comparison shows a close similarity in the packing of molecules of three of them (i.e., 3, 4, 6) that form the π-stacks along the shortest crystallographic axes, with a substantial spatial overlap between adjacent molecules in the stacks, depending mainly on the length of substituent at position 9 of carbazole skeleton and on the ratio of (%C···H)/(%C···C) interactions. Similar to them, in the crystal structures of 1 and 2 there is slipped face-to-face π···π interaction, but in contrast this interaction connects two molecules of these compounds into the dimers that are further connected by C–H···π interaction. The molecular packing in crystals of these compounds is intermediate between the arrangement of molecules of 3, 4, and 6, where the slipped π-stacking is predominant, and the typical herringbone packing in compounds 5 and 7–10. Thus, it can be supposed that out of ten compounds analyzed here, only 3, 4, and 6 will turn to be the most promising materials for device applications (particularly for field-effect transistors).

Unraveling Interactions in Molecular Crystals Using Dispersion Corrected Density Functional Theory: The Case of the Epoxydihydroarsanthrene Molecules.

Noncovalent interactions are prevalent in crystal packing and supramolecular chemistry. Directional noncovalent interactions such as donor-acceptor bonds (e.g., hydrogen, chalcogen, and pnictogen bonds) as well as nondirectional forces (such as dispersion) come together to stabilize supramolecular assemblies by striking a delicate energetic balance. Typically, a two-pronged approach employing experimental X-ray structures and gas phase quantum chemical modeling has been used to understand and design supramolecular architectures. Drawing from recent advances in molecular crystal modeling with dispersion corrected density functional theory (DFT), we propose in this article a combination of qualitative noncovalent index (NCI) analysis and periodic and gas phase DFT calculations on substitutional crystal analogues to unravel the dominant interactions in a particular crystal packing. We illustrate the possibilities of this approach by studying three crystal packings of epoxydihydroarsanthrene analogues that present a complex combination of donor-acceptor interactions including pnictogen-pnictogen, pnictogen-π, and pnictogen-chalcogen. We show that, in these crystals, the chalcogen-pnictogen interaction dominates over the pnictogen-pnictogen and pnictogen-π. In the latter, the role of donor and acceptor is reversed depending on the interacting moieties. Multiple chalcogen-pnictogen interactions necessitate larger donor atoms, such as sulfur. These observations explain and rationalize the experimentally observed crystal structures.

Topology of the interactions pattern in pharmaceutically relevant polymorphs of methylxanthines (caffeine, theobromine, and theophiline): combined experimental (¹H-¹⁴N nuclear quadrupole double resonance) and computational (DFT and Hirshfeld-based) study.

Three anhydrous methylxanthines: caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) and its two metabolites theophylline (1,3-dimethylxanthine; 1,3-dimethyl-7H-purine-2,6-dione) and theobromine (3,7-dimethyl-xanthine; 3,7-dimethyl-7H-purine-2,6-dione), which reveal multifaceted therapeutic potential, have been studied experimentally in solid state by (1)H-(14)N NMR-NQR (nuclear magnetic resonance-nuclear quadrupole resonance) double resonance (NQDR). For each compound the complete NQR spectrum consisting of 12 lines was recorded. The multiplicity of NQR lines indicates the presence of a stable β form of anhydrous caffeine at 233 K and stable form II of anhydrous theobromine at 213 K. The assignment of signals detected in NQR experiment to particular nitrogen atoms was made on the basis of quantum chemistry calculations performed for monomer, cluster, and solid at the DFT/GGA/BLYP/DPD level. The shifts due to crystal packing interactions were evaluated, and the multiplets detected by NQR were assigned to N(9) in theobromine and N(1) and N(9) in caffeine. The ordering theobromine > theophylline > caffeine site and theophylline < theobromine < caffeine according to increasing electric field gradient (EFG) at the N(1) and N(7) sites, respectively, reflects the changes in biological activity profile of compounds from the methylxanthines series (different pharmacological effects). This difference is elucidated on the basis of the ability to form intra- and intermolecular interactions (hydrogen bonds and π···π stacking interactions). The introduction of methyl groups to xanthine restricts the ability of nitrogen atoms to participate in strong hydrogen bonds; as a result, the dominating effect shifts from hydrogen bond (theobromine) to π···π stacking (caffeine). Substantial differences in the intermolecular interactions in stable forms of methylxanthines differing in methylation (site or number) were analyzed within the Hirshfeld surface-based approach. The analysis of local environment of the nitrogen nucleus permitted drawing some conclusions on the nature of the interactions required for effective processes of recognition and binding of a given methylxanthine to A1-A(2A) receptor (target for caffeine in the brain). Although the interactions responsible for linking neighboring methylxanthines molecules in crystals and methylxanthines with targets in the human organism can differ significantly, the knowledge of the topology of interactions provides reliable preliminary information about the nature of this binding.

Crystal and Molecular Structure of Two Organic Salts from 3,5-Dimethylpyrazole and Organic Acids

Two compounds (3,5-dimethylpyrazole): (4-nitro-phthalic acid) (1) [(HL)+·(Hnpa)−, Hnpa = 4-nitro-hydrogenphthalate], and (3,5-dimethylpyrazole): (naphthalene-1,5-disulfonic acid) (2) [(HL+)2·(nds2−), nds2− = 1,5-naphthalenedisulfonate] were obtained from self-assembly of the corresponding acids with the 3,5-dimethylpyrazole, and their structures were fully characterized. Both compounds are ionic, with proton transfer occurring to the N of the 3,5-dimethylpyrazole moiety. The two structures adopted hetero supramolecular synthons. Compound 1 crystallizes in the monoclinic, space group P2(1), with a = 7.843(3) A, b = 6.8506(12) A, c = 12.816(2) A, β = 92.0710(10)°, V = 688.1(3) A3, Z = 2. Compound 2 crystallizes in the triclinic, space group P-1, with a = 8.0883(13) A, b = 8.2960(15) A, c = 8.9223(14) A, α = 75.502(14)°, β = 89.975(13)°, γ = 80.197(14)°, V = 570.60(16) A3, Z = 1. Supramolecular architectures of the compounds 1–2 involve O–H···O/N–H···O/N–H···S hydrogen bonds as well as other noncovalent associations. The role of these noncovalent interactions in the crystal packing is analysed. Both salts displayed 3D framework structure for the synergistic effect of the various noncovalent interactions. The crystal structures of the 3,5-dimethylpyrazole salts with 4-nitro-phthalic acid, and naphthalene-1,5-disulfonic acid show extensive hydrogen bonding as well as C–H···O, CH3···O, and C···π interections, giving three-dimensional networks.

Surprising base pairing and structural properties of 2'-trifluoromethylthio-modified ribonucleic acids.

The chemical synthesis of ribonucleic acids (RNA) with novel chemical modifications is largely driven by the motivation to identify eligible functional probes for the various applications in life sciences. To this end, we have a strong focus on the development of novel fluorinated RNA derivatives that are powerful in NMR spectroscopic analysis of RNA folding and RNA ligand interactions. Here, we report on the synthesis of 2′-SCF3 pyrimidine nucleoside containing oligoribonucleotides and the comprehensive investigation of their structure and base pairing properties. While this modification has a modest impact on thermodynamic stability when it resides in single-stranded regions, it was found to be destabilizing to a surprisingly high extent when located in double helical regions. Our NMR spectroscopic investigations on short single-stranded RNA revealed a strong preference for C2′-endo conformation of the 2′-SCF3 ribose unit. Together with a recent computational study (L. Li, J. W. Szostak, J. Am. Chem. Soc. 2014, 136, 2858–2865) that estimated the extent of destabilization caused by a single C2′-endo nucleotide within a native RNA duplex to amount to 6 kcal mol−1 because of disruption of the planar base pair structure, these findings support the notion that the intrinsic preference for C2′-endo conformation of 2′-SCF3 nucleosides is most likely responsible for the pronounced destabilization of double helices. Importantly, we were able to crystallize 2′-SCF3 modified RNAs and solved their X-ray structures at atomic resolution. Interestingly, the 2′-SCF3 containing nucleosides that were engaged in distinct mismatch arrangements, but also in a standard Watson–Crick base pair, adopted the same C3′-endo ribose conformations as observed in the structure of the unmodified RNA. Likely, strong crystal packing interactions account for this observation. In all structures, the fluorine atoms made surprisingly close contacts to the oxygen atoms of the corresponding pyrimidine nucleobase (O2), and the 2′-SCF3 moieties participated in defined water-bridged hydrogen-bonding networks in the minor groove. All these features allow a rationalization of the structural determinants of the 2′-SCF3 nucleoside modification and correlate them to base pairing properties.

Quantitative crystal structure analysis of fluorinated porphyrins

Herein, we report a series of fluorinated porphyrins, 5,10,15,20-tetrakis(2′,6′-difluorophenyl)porphyrin, MT(2′,6′-DFP)P where M=2H, 1; Co(II)·(MeOH)2, 2; Cu(II), 3; Zn(II)·(MeOH)2, 4 and Zn(II)·(THF)3, 5 have been structurally characterized by single crystal X-ray diffraction analysis. All the compounds are crystallized in monoclinic crystal system and the crystal structures of 2, 4 and 5 features octahedral geometry whereas 3 exhibits square planar geometry. The compounds 1, 3 and 2, 4 are isostructural, show similar molecular crystal packing and comparable intermolecular interactions. The supramolecular self assembly of compounds 1–5 is dominated by a variety of intermolecular interactions such as CH⋯F, CH⋯π, CF⋯π and F⋯F. Furthermore, the role of weak intermolecular interactions in the crystal packing has been analysed and quantified using Hirshfeld surface analysis.

Supramolecular architectures ofN-acetyl-L-proline monohydrate andN-benzyl-L-proline

The title compounds, N-acetyl-L-proline monohydrate, C7H11NO3·H2O, (I), and N-benzyl-L-proline, C12H15NO2, (II), crystallize in the monoclinic space group P21 with Z' = 1 and Z' = 2, respectively. The conformation of C(γ) with respect to the carboxylic acid group in (I) is C(γ)-exo or UP pucker, with the pyrrolidine ring twisted, while in (II), it is C(γ)-endo or DOWN, with the pyrrolidine ring assuming an envelope conformation. The crystal packing interactions in (I) are composed of two substructures, one characterized by an R6(6)(24) motif through O-H...O hydrogen bonds and the other by an R4(4)(23) ring through C-H...O interactions. In (II), the crystal packing interactions consist of N-H...O and C-H...O hydrogen bonds. Proline (Pro) exists in its neutral form in (I) and is zwitterionic in (II). This difference in the ionization states of Pro is manifested through the absence of N-H...O and presence of O-H...O interactions in (I), and the presence of N-H...O and absence of O-H...O hydrogen bonds in (II). While C-H...O interactions are present in both (I) and (II), the geometry of the synthons formed by them and their mode of participation in intermolecular interactions is different. Though the title compounds differ significantly in terms of modifications in the Pro skeleton, the differences in their supramolecular structures may also be viewed as a result of the molecular recognition facilitated by the presence of a solvent water molecule in (I) and the zwitterionic state of the amino acid in (II).

Strategies for crystallizing a chromatin protein in complex with the nucleosome core particle

The molecular details of how chromatin factors and enzymes interact with the nucleosome are critical to understanding fundamental genetic processes including cell division and gene regulation. A structural understanding of such processes has been hindered by the difficulty in producing diffraction-quality crystals of chromatin proteins in complex with the nucleosome. We describe here the steps used to grow crystals of the 300-kDa RCC1 chromatin factor/nucleosome core particle complex that diffract to 2.9-Å resolution. These steps include both pre- and postcrystallization strategies potentially useful to other complexes. We screened multiple variant RCC1/nucleosome core particle complexes assembled using different RCC1 homologs and deletion variants, and nucleosomes containing nucleosomal DNA with different sequences and lengths, as well as histone deletion variants. We found that using RCC1 from different species produced different crystal forms of the RCC1/nucleosome complex consistent with key crystal packing interactions mediated by RCC1. Optimization of postcrystallization soaks to dehydrate the crystals dramatically improved the diffraction quality of the RCC1/nucleosome crystal from 5.0- to 2.9-Å resolution.