Supramolecular architectures of functionalized tetraphenylmetalloporphyrins in crystalline solids. Studies of the 4-methoxyphenyl, 4-hydroxyphenyl and 4-chlorophenyl derivatives

Abstract

A series of new ‘inclusion’ materials based on tetra-4-methoxyphenyl, tetra-4-hydroxyphenyl and tetra-4-chlorophenyl derivatives of the metalloporphyrin system, in combination with a wide variety of guest molecules and ligands, have been prepared, and their structural systematics analysed. Crystallographic investigations have confirmed that the supramolecular arrangement of the hydroxyphenylporphyrin species is dominated by interporphyrin directional hydrogen-bonding interactions, and consists of continuous networks of strongly coordinated entities with varying degrees of cross-linking and rigidity. Guest molecules can be absorbed in these solids in distinctly defined sites of the lattice: in the small interhost cages of fixed size between adjacent intercoordinated porphyrin hosts, or in extended one-dimensional channels formed between the hydrogen bonded host arrays running parallel or perpendicular to the porphyrin plane. For polar ligands with strong nucleophiles, their potential coordination to the metal center provides an additional recognition factor. The stacking mode (offset geometry or overlapping) of the host metalloporphyrin arrays is also affected by the nature of the incorporated guest/ligand. Materials based on the chloro-substituted porphyrins were found to form similarly networked structural modes, influenced by the molecular shape as well as by halogen-halogen noncovalent interactions. Formation of a polar tubular intermolecular architecture capable of aligning organic dipolar guest molecule in the crystal bulk has also been demonstrated. The methoxy-substituted materials form clathrate-type structures characterized by dense layered arrangement of the porphyrin building blocks in two-dimensions. The various structural features directing the observed modes of the supramolecular architecture, and affecting the host structure as well as the guest mobility in it, are discussed.     

Host–Guest Complexation Using Pillar[5]arene Crystals: Crystal-Structure Dependent Uptake,Release, and Molecular Dynamics of an Alkane Guest

Host–guest complexation has been mainly investigated in solution, and it is unclear how guest molecules access the assembled structures of host and dynamics of guest molecules in the crystal state. In this study, we studied the uptake, release, and molecular dynamics of n-hexane vapor in the crystal state of pillar[5]arenes bearing different substituents. Pillar[5]arene bearing 10 ethyl groups yielded a crystal structure of herringbone-type 1:1 complexes with n-hexane, whereas pillar[5]arene with 10 allyl groups formed 1:1 complexes featuring a one-dimensional (1D) channel structure. For pillar[5]arene bearing 10 benzyl groups, one molecule of n-hexane was located in the cavity of pillar[5]arene, and another n-hexane molecule was located outside of the cavity between two pillar[5]arenes. The substituent-dependent differences in molecular arrangement influenced the uptake, release, and molecular dynamics of the n-hexane guest. The substituent effects were not observed in host–guest chemistry in solution, and these features are unique for the crystal state host–guest chemistry of pillar[5]arenes.     

Host Perturbation in a β‐Hydroquinone Clathrate Studied by Combined X‐ray/Neutron Charge‐Density Analysis: Implications for Molecular Inclusion in Supramolecular Entities

X‐ray/neutron (X/N) diffraction data measured at very low temperature (15 K) in conjunction with ab initio theoretical calculations were used to model the crystal charge density (CD) of the host–guest complex of hydroquinone (HQ) and acetonitrile. Due to pseudosymmetry, information about the ordering of the acetonitrile molecules within the HQ cavities is present only in almost extinct, very weak diffraction data, which cannot be measured with sufficient accuracy even by using the brightest X‐ray and neutron sources available, and the CD model of the guest molecule was ultimately based on theoretical calculations. On the other hand, the CD of the HQ host structure is well determined by the experimental data. The neutron diffraction data provide hydrogen anisotropic thermal parameters and positions, which are important to obtain a reliable CD for this light‐atom‐only crystal. Atomic displacement parameters obtained independently from the X‐ray and neutron diffraction data show excellent agreement with a |ΔU| value of 0.00058 Ų indicating outstanding data quality. The CD and especially the derived electrostatic properties clearly reveal increased polarization of the HQ molecules in the host–guest complex compared with the HQ molecules in the empty HQ apohost crystal structure. It was found that the origin of the increased polarization is inclusion of the acetonitrile molecule, whereas the change in geometry of the HQ host structure following inclusion of the guest has very little effect on the electrostatic potential. The fact that guest inclusion has a profound effect on the electrostatic potential suggests that nonpolarizable force fields may be unsuitable for molecular dynamics simulations of host–guest interaction (e.g., in protein–drug complexes), at least for polar molecules.     

Inclusion Compounds of Nitrosobenzenes with Cholic Acid and Deoxycholic Acid

The crystalline inclusion compounds of cholic acid (CA) and deoxycholic acid (DCA) with several nitrosobenzenes were prepared. The IR spectra and crystal structures of these compounds confirmed inclusion of the monomeric form of the C-nitroso compounds. The DCA compounds have 2 : 1 host:guest stoichiometry and P2₁ symmetry. Guest molecules are enclosed in channels and disordered. In the CA-nitrobenzene inclusion compound (1·CA) the host:guest stoichiometry is 1 : 1. The host molecules form typical CA bilayer aggregates and guest molecules are accommodated in helicoidal channels. The guest nitroso group is not coplanar with the phenyl ring; the torsion angle on the C–N bond is 8.6(8)°. The solid-state circular dichroism spectrum of 1·CA shows the negative Cotton effect at 780 nm corresponding to the n–^* electronic transition that can be associated with the P helicity of the guest molecule. The extremely weak magnitude of the Cotton effects exhibited by the DCA complexes points to a nearly planar arrangement of the NO group and the phenyl ring in the guest molecules.     

Inclusion compounds with the drug 5-Methoxysulphadiazine: Structures,thermodynamics of decomposition and relationship to polymorphism of the sulphonamide

Abstract

The structures and thermal decompositions of the solvates of 5-methoxysulphadiazine with dioxane, chloroform and tetrahydrofuran have been investigated by X-ray analysis, differential scanning calorimetry and thermogravimetry. These species are clathrates with 1:1 host-guest stoichiometry crystallizing in space group P2₁/c with very similar unit cell parameters. Their structures are based on a common isostructural host framework in which the guest molecules occupy channels with the narrowest constriction being 2 Å. The unusual stability of these species and their decomposition to a common polymorph (Form I) of 5-methoxysulphadiazine are rationalized on the basis of crystal packing analysis, potential energy calculations and estimates of the activation energy for desolvation. Hydrogen bonding patterns between host molecules in the clathrates are compared with those occurring in two polymorphic forms of the parent sulphonamide.     

New Bis- and Tris-Ferrocenoyl and Tris-Benzoyl Lower-rim Substituted Calix[5]arene Esters: Synthesis,Electrochemistry and X-ray Crystal Structures

Abstract

New tris-benzoyl-, tris-ferrocenoyl- and bis-ferrocenoyl p-tert-butylcalix[5]arene esters have been synthesised (1–3 respectively) by reaction of the parent calixarene with the appropriate acid chloride. X-ray crystal structures of all three compounds have been determined with the structure of 2 revealing an ethanol guest molecule bound deep in the cavity of the calix[5]arene. The electrochemical properties of 2 have been extensively investigated using rotating disk electrode, cyclic and square wave voltammetric techniques. Electrochemical evidence is presented suggesting 2 has the capability of detecting neutral polar guest molecules, such as dimethylformamide, in dichloromethane solutions.     

Crystal structure of inclusion compounds: The complexes of thecis-syn-cis and thecis-anti-cis isomers of dicyclohexano-18-crown-6 with 4-methylbenzenesulfamide

The crystal structure of two complexes of the isomerscis-syn-cis (isomer A) andcis-anti-cis (isomer B) of dicyclohexano-18-crown-6 with 4-methylbenzenesulfamide have been determined by X-ray single crystal diffraction methods. The two structures have been solved by direct methods and refined to agreement values of 0.067 and 0.038 for isomers A and B respectively. The first isomer forms an inclusion compound with a host/guest ratio of 1 : I; the second one of I:2. The amino groups of the guest molecules are connected by N-H...O hydrogen bonds with oxygen atoms of the polyether molecules. The methyl groups of 4-methylbenzenesulfamide do not form hydrogen bonds.[/p]The host-guest interactions in the molecular complexes, the reciprocal influence of the two molecules on their conformation and the intermolecular contacts between the molecules in the crystal are discussed.     

Diverse Modes of Guest Inclusion in a Cyclodextrin: X-ray Structural and Thermal Characterization of a 4:3 β-cyclodextrin—Cyclizine Complex

Abstract

1-Diphenylmethyl-4-methylpiperazine (cyclizine) is an antiemetic drug which forms an inclusion complex with β-cyclodextrin of formula (β-cyclodextrin)₄ · (cyclizine)₃ · 50H₂O. This species crystallizes in the monoclinic space group P2₁ with a = 15.246(1), b = 65.075(5), c = 15.609(1) Å, β = 102.62(1)° and Z = 2 formula units. Complex water content and the host:drug stoichiometric ratio were determined by thermogravimetry and UV spectrophotometry respectively. Differential scanning calorimetry showed that the crystals dehydrate in at least two stages and begin to decompose from approximately 250°C. The crystal structure was solved by a combination of Patterson search and direct methods. Isotropic refinement converged at R = 0.094 for 8806 reflections with I > 2σ(I). The unusual stoichiometry is accounted for as follows: the four β-cyclodextrin molecules comprising the asymmetric unit occur as two independent head-to-head dimers, each formed by O—H…O hydrogen bonding across the macro-cyclic secondary surfaces. One dimer contains two cyclizine guest molecules in head-to-tail orientation, thus accounting for two distinct modes of drug inclusion. In the second dimer, only one β-cyclodextrin molecule is significantly occupied by a cyclizine molecule (in a mode analogous to one of those in the first dimer), the other half of the dimer being largely devoid of guest. A possible mechanism for the formation of this unusual structure is proposed and the crystal packing arrangement is shown to be based on a novel disrupted tetrameric channel motif.     

Comparative X-ray structural study of laterally mono-ethyl substituted 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra-methoxycalix[4]arene and its non-substituted parent compound including guest free and solvated forms. Chemical straightening of guest channels

Three solvate crystal structures of the laterally ethyl substituted tetra-tert-butyltetramethoxycalix[4]arene 1 [(1·THF (1a), 1·CHCl₃ (1b) and 1·CH₂Cl₂ (1c)] are compared to the corresponding solvent-free structure (1) using single crystal X-ray structure determination, isostructurality and molecular isometricity calculations. To study the effect of the lateral substitution, the laterally non-substituted host with the guest THF (2a) is also included to the comparison. The calixarene molecules in the different structures all adopt the partial cone conformation with different affection of the respective guest molecules, always being positioned interstitially. Depending on the lateral substitution and the size of the included guests, the molecular conformation of the calix[4]arene shows small differences relating to the alignment of the arene units. The channels disposable of the solvent guest molecules in the crystal structures straighten as the effect of lateral substitution of the host calix[4]arene. The orthorhombic crystal structures of 1a–c are isostructural irrespective of the included solvent molecules, while 1 and 2a crystallise in the same monoclinic space group.     

The structure - properties relations in the clathrates of N1 (NCS)2 (4-methylpyridine)4

The Ni(NCS)₂(4-methylpyridine)₄ molecule shows significant confomational flexibility of the four piooline and the two isothiocyanate ligands. Both intramolecular non-bonded energy calculations and x-ray crystal structures support the idea that the host molecule may adopt different conformations (molecular shape) in order to bind, in clathrate formation, guest molecules of different shape and size. This versatility enables the Ni(NCS)₂(4-methylpyridine)₄ complex to form many different crystal structures able to absorb both small molecules, e.g. noble gases, and relatively large condensed aromatic hydrocarbons. The type of the crystalline structure formed defines “primary” properties of the clathrate. Secondary effects are observed when varying lattice parameters of the host structure (dilatation - contraction) by introducing guest component of suitable composition.     

X-ray Structure of a 1:2 Complex of Hexakis (3-O-acetyl-2,6-di-O-methyl)-α-cyclodextrin with Butylacetate

Abstract

Crystal structure of a 1:2 complex of hexakis(3-O-acetyl-2,6-di-O-methyl)-α-cyclodextrin (ADMACD) with butylacetate was determined by the X-ray method. The space group of the crystal is P2₁2₁2₁ with Z = 4 and D _x = 1.293 g cm^?3, and the cell dimensions are a = 11.087(2), b = 23.543(3), and c = 31.739(6) Å. The structure was solved by the direct method and refined to the R-value of 0.123 for all the 4993 observed reflections with 1<0. The ADMACD molecule is in a round shape with the pseudo hexagonal symmetry. Methyl and acetyl groups point towards the outside of the molecule. Because of the acetyl groups attached to O3 and methyl groups attached to O6, the intramolecular cavity is ca. 3 Å deeper than the cavity of native α-CD. One butylacetate molecule is coaxially accommodated with its acetyl group at the O6 side in the host cavity while the other guest molecule is located in an intermolecular space between host molecules which are stacked to form a head-to-tail channel-type packing structure along the a axis.     

Crystal structures of dibenzo-14-crown-4 alcohol and diol monohydrates

Monohydrate complexes1–3 ofsym-hydroxydibenzo-14-crown-4,sym-cis-dihydroxydibenzo-14-crown-4 andsym-trans-dihydroxydibenzo-14-crown-4, respectively, have been prepared and their solid state structures determined. For all three complexes the space group wasCmc2₁. The crystal data are: for1,a=16.256(10),b=12.076(5),c=8.767(3) Å,V=1721.0 ų withZ=4; for2,a=16.437(3),b=11.997(4),c=8.640(3) Å,V=1703.8 ų withZ=4; for3,a=16.528(7),b=12.306(3),c=8.540(3) Å,V=1737.0 ų withZ=4. The structures were refined to [R, R _w, unique data withF<n (F)]: for1, 0.066, 0.055, 828, 2.5; for2, 0.034, 0.035, 1090, 3.0; for3, 0.047, 0.036, 1038, 3.0. The three crystal structures have a high degree of isomophism and the dibenzo-14-crown-4 units in the three host-guest complexes are nearly identical. Intramolecular hydrogen bonds link an alcohol oxygen atom of the host to the oxygen atom of the guest water molecule and the oxygen atom of the guest water molecule to ether oxygen atoms of the host in1–3. In2 and3, there is an intermolecular hydrogen bond between the hydrogen atom of an alcohol group of the host and the oxygen atom of a symmetry-related water molecule guest of another complex.     

Paraquat guest induced hydrogen-bonding modes of a hydrazide-derived bis(meta-phenylene)-32-crown-10 host in the solid state

A hydrazide-derived bis(meta-phenylene)-32-crown-10 host showed a dimeric structure via quadruple N-H?O hydrogen bonds, but a polymeric structure via two N-H?O hydrogen bonds and two C-H?O hydrogen bonds at each knot in the presence of paraquat in the solid state, which led to a novel poly(taco complex) and ordering arrangement of the guest molecules indirectly.     

Molecular recognition in cyclodextrin complexes of amino acid derivatives: the effects of kinetic energy on the molecular recognition of a pseudopeptide in a nonconstraining host environment as revealed by a temperature-dependent crystallographic study

The crystal structure of a triclinic 2:2 inclusion complex of beta-cyclodextrin with N-acetyl-L-phenylalanine methyl ester has been determined at several temperatures between 298 and 20 K to further study molecular recognition using solid-state supramolecular beta-cyclodextrin complexes. The study reveals kinetic energy dependent changes in guest molecule conformations, orientations, and positions in the binding pocket presented by the crystal lattice. Accompanying these changes are observable differences in guest-guest interactions and hydrogen-bonding interactions in the binding pocket that involve guest molecules, water of hydration molecules, and beta-cyclodextrin molecules. On the basis of the differences observed in the crystal structures, we present a solid-state example of a system that displays the properties of both classical and quantum chemical models. At higher temperatures, the structure conforms to a classical mechanical model with dynamic disorder. At lower temperatures, the observations conform to examples in which there is static disorder representative of models in which quantum states differing in conformation, position, and orientation of components in the crystal structure are occupied. Ab initio theoretical calculations on the different guest molecule conformations have been carried out. Superpositions of theoretical electrostatic surface potential diagrams on the observed molecular positions in the complexes provide confidence that the deconvolution of the guest molecule disorder is acceptable. Temperature-dependent solid-state magic angle spinning deuteron NMR measurements provide evidence for large-amplitude, diffusive motion on a microsecond time scale in the complex.     

Chiral crystalline hosts derived from lactic acid.* X-ray crystal structures of optically resolved and racemic host compound 1,1-diphenyl-1,2-propanediol and a 2:1 complex between optically resolved host and 3-picoline

Abstract

The X-ray crystal structures of racemic (1) and S-1,1-diphenyl-1,2-propanediol (2), and of a 2:1 inclusion complex (3) of 2 with 3-picoline are reported. Three different binding schemes characterize the packing of these structures. Only one of the two hydroxy groups (that which is not related to the asymmetric carbon) is involved in O-H…O hydrogen bonds responsible for the formation of dimers and chains in 1 and 2, leaving the other OH group for stabilization of dimers through OH…phenyl interactions in 1 or free of interactions in 2. In the crystal structure of the chiral complex 3, the hydroxy groups link the two independent host molecules, A and B, the 3-picoline guest to the B host molecule, and a remaining one forms H-bonded chains along the c axis.     

Cup-shaped E,E-stilbenophane: synthesis,crystal structure and supramolecular chemistry

A new E,E-stilbenophane was synthesised and characterised. The crystal structure of this cyclophane shows that this molecule has a cup-shaped structure, which hosts a phenyl ring of neighbouring molecule as guest in its cavity with a π–π distance of about 3.7 Å. Moreover, the NMR spectra and theoretical analysis (gauge-independent atomic orbitals (GIAO) and quantum theory of atoms in molecules (QTAIM)) suggest that the silver recognition by E,E-stilbenophane host molecules is based on cation–π interactions in which the π-electrons of the double bonds play a major role.     

Electron distribution in 1-organo-1H-tetrazole-5-thiols. Crystal and molecular structure of 1-methyl-1H-tetrazole-5-thiol and its potassium (18-crown-6) salt

The crystal and molecular structures of both neutral and anionic 1-methyl-1H-tetrazole-5-thiol, as its potassium(18-crown-6) salt, are reported. In the solid state, the molecular thiotetrazole adopts a planar, dimeric arrangement, in which two neighboring molecules are hydrogen bridged. Each monomeric unit exhibits considerable π electron delocalization over the CN₂S fragment. The anionic form displays extensive, but not uniform, π electron delocalization within the ring, which also extends to the exocyclic carbon–sulfur bond, the structure being best described as a hybrid. The potassium cation is coordinated to the macrocyclic 18-crown-6 ether as expected, but it also interacts with the NCS fragment of the tetrazolethiolate ring.     

Heterocalixarene Inclusion Chemistry. Structure of a Crystalline Host-Guest Complex Including endo-Calix Ethyl Acetate and exo-Calix Clustering of Water

The X-ray crystal structure of the solvent inclusion compound formed between heterocalix[8]arene 1, ethyl acetate and water (1 : 1 : 4.5) has been studied. The compound crystallized in tetragonal space group I4₁/a, a = b = 21.278(3), c = 31.290(4) Å, V = 14167(4) ų, Z = 8. The host molecule, incorporating benzimidazol-2-one and 2,5-dimethoxy-1,3-phenylene subunits in an alternate cyclic arrangement, forms an almost perfectly closed cavity which encapsulates one solvent ethyl acetate guest molecule. Water molecules being entrapped in the lattice cages in the form of cyclic and linear clusters bind the bulky inclusion complexes via H-bonds in infinite layers. Two symmetry center related benzimidazole-2-one moieties of two hosts from neighbouring layers in the crystal lattice are arranged such that they partially overlap exhibiting stacking interaction.     

Effect of Guest–Host Hydrogen Bonding on the Structures and Properties of Clathrate Hydrates

To provide improved understanding of guest–host interactions in clathrate hydrates, we present some correlations between guest chemical structures and observations on the corresponding hydrate properties. From these correlations it is clear that directional interactions such as hydrogen bonding between guest and host are likely, although these have been ignored to greater or lesser degrees because there has been no direct structural evidence for such interactions. For the first time, single‐crystal X‐ray crystallography has been used to detect guest–host hydrogen bonding in structure II (sII) and structure H (sH) clathrate hydrates. The clathrates studied are the tert‐butylamine (tBA) sII clathrate with H₂S/Xe help gases and the pinacolone + H₂S binary sH clathrate. X‐ray structural analysis shows that the tBA nitrogen atom lies at a distance of 2.64 Å from the closest clathrate hydrate water oxygen atom, whereas the pinacolone oxygen atom is determined to lie at a distance of 2.96 Å from the closest water oxygen atom. These distances are compatible with guest–water hydrogen bonding. Results of molecular dynamics simulations on these systems are consistent with the X‐ray crystallographic observations. The tBA guest shows long‐lived guest–host hydrogen bonding with the nitrogen atom tethered to a water HO group that rotates towards the cage center to face the guest nitrogen atom. Pinacolone forms thermally activated guest–host hydrogen bonds with the lattice water molecules; these have been studied for temperatures in the range of 100–250 K. Guest–host hydrogen bonding leads to the formation of Bjerrum L‐defects in the clathrate water lattice between two adjacent water molecules, and these are implicated in the stabilities of the hydrate lattices, the water dynamics, and the dielectric properties. The reported stable hydrogen‐bonded guest–host structures also tend to blur the longstanding distinction between true clathrates and semiclathrates.