The crystal and molecular structure of 1-methyl-3-carbamoyl-pyridinium:indole-3-acetic acid (1:1) monohydrate complex. A model for the intermolecular stacking interaction between the indole ring and NAD+.

The crystal and molecular structure of the title complex has been determined by X-ray diffraction methods. The crystals contain one water molecule per asymmetric unit, which plays a important role in the molecular packing by forming hydrogen bonds with two carboxyl oxygen atoms of indole-3-acetic acid and a carbamoyl nitrogen atom of the 1-methyl-3-carbamoylpyridinium cation. Prominent stacking between the indole ring and the pyridinium ring, caused by the π_D?π_A interaction, is observed. This overlap with substantial result may provide a model for the stacking interaction between NAD⁺ and the tryptophanyl residues in the proteins.     

Ferriprotoporphyrin IX Oxygen Activation/Insertion Reactions: The Nature of the Interaction between Ferriprotoporphyrin IX and Aniline (Substrate)

The interaction between aniline and ferriprotoporphyrin IX in alkaline solution has been investigated using pyridine and the N-methyl pyridinium ion as site-specific inhibitors of oxygen activation. Pyridine inhibits oxygen activation in a noncompetitive manner with respect to aniline (K₁ = 1.24 mol ⁻¹ dm³ at 30°C) while the N-methyl pyridinium ion inhibited in a manner consistent with two sites for aniline binding, only one of which was competitively inhibited (K₁ = 317mol^-l dm³ at 30°C). A comprehensive reinvestigation of the interaction of pyridine and N-methyl pyridinium ions with alkaline ferriprotoporphyrin IX has shown that two molecules of each ligand bind per hemin dimer in a strongly cooperative manner. The association constant for the first pyridinium ion bound is K_1a = 176 mol⁻¹ dm³ at 30°C, while that for the first pyridine molecule bound is K_1a = 0.580 mol⁻¹ dm³ at 30°C; these are both close to the observed inhibition association constants (K₁). Thermodynamic parameters for the interactions have been evaluated and compared to previous literature values. On the basis of these results a model is proposed for aniline interaction with the ferriprotoporphyrin dimer IX which involves the binding of two molecules of aniline to the ferriprotoporphyrin IX tetrapyrrole ring system by planar π bonding interactions with the rings having the propionate groups attached.     

Inhibitors of HIV-1 attachment. Part 3: A preliminary survey of the effect of structural variation of the benzamide moiety on antiviral activity

1-(4-Benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (1a) has been characterized as an inhibitor of HIV-1 attachment that interferes with the interaction of viral gp120 with the host cell receptor CD4. In previous studies, the effect of indole substitution pattern on antiviral activity was probed. In this Letter, the effect of structural variation of the benzamide moiety is described, a study that reveals the potential or the phenyl moiety to be replaced by five-membered heterocyclic rings and a restricted tolerance for the introduction of substituents to the phenyl ring.     

An X-ray evidence for the ring-stacking interaction between indole ring and the pyrimidine moiety of thiamin: Crystal structure of thiamin indole-3-propionate

The crystal structure of thiamin indole-3-propionate was determined by X-ray diffraction as a model for the possible thiamin coenzyme-tryptophan residue interaction at the binding site of thiamin pyrophosphate dependent enzymes. There is an intermolecular stacking interaction of the indole ring with the pyrimidine ring, but not with the positively charged thiazolium ring, of thiamin retaining the characteristic F-conformation. Although this association is due to dipole-dipole interaction between both aromatic rings, charge-transfer interaction cannot be ruled out in solution state because the absorption spectrum shows the characteristic charge-transfer band.     

On the interaction between flavin-adenine rings and between flavin-indole rings by X-ray structural studies

Two crystal structures of 7,8-dimethylisoalloxazine-10-acetic acid:adenine-9-ylethylamine(1:1)heptahydrate and 7,8-dimethylisoalloxazine-10-acetic acid:l-tryptophan methylester(1:1)heptahydrate complexes were determined as models for the flavin-adenine and flavin-indole interactions, respectively. In the former complex, both molecules were connected by Hoogsteen-type hydrogen bonds between the pyrimidinoid portion of flavin and the adenine, in addition to the normal stacking of both aromatic rings. On the other hand, parallel stackings and intermolecular vertical spacings less than the normal van der Waals separation distance were observed between the flavin and indole rings of the latter complex, indicative of the π_D-π_A charge-transfer interaction in their ground states. Comparing with the X-ray findings of related complexes, we discussed the interaction modes between flavin and adenine rings and between flavin and indole rings.     

The crystal and molecular structure of methyl 2,4,6-tri-O-acetyl-3-O(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl)-β-d-glucopyranoside (methyl 2,3,4,6,2′,4′,6′,-hepta-O-acetyl-β-d-laminarabioside)

The crystal and molecular structure of methyl 2,3,4,6,2′,4′,6′-hepta-O-acetyl β-laminarabioside has been determined by X-ray diffraction. The crystal belongs to the orthorhombic system space group P2₁2₁2₁,a 10.471 (1), b 22.482(1), c 13.647(1) Å, D_m 1.33 g.cm^?3, Z 4. The structure was established by the direct method and refined by the block-diagonal, least-squares procedure to R 0.093 for 2043 observed reflections. Difference synthesis showed all the hydrogen atoms except the methyl hydrogen ones. The molecule shows a fully-extended conformation and has no intra-molecular hydrogen bond. The ring-to-ring conformation can be described.as (φψ)  (42.5, 4.7°), according to the definition of Sathyanarayana and Rao, and it is compared with (φψ)  (27.9, ?37.5°) of laminarabiose. There is no inter-molecular hydrogen bond. The d-glucopyranose rings of the molecule are piled up along the a axis and approximately parallel to the bc-plane. Each of the acetyl groups is approximately perpendicular to the d-glucopyranose ring.     

Amido binding to ReO core: Synthesis, structure and intermolecular interactions

The light green coloured complexes of general formula [Re^VO(L)Cl(OH₂)]Cl have been synthesised in good yields by reacting [Re^VOCl₃(AsPh₃)₂] with HL in dichloromethane in dinitrogen atmosphere. Here, L⁻ is the deprotonated form of N,N-bis(2-pyridylmethyl)amine (HL¹); N-(2-pyridylmethyl)-N′,N′-dimethylethylenediamine (HL²) and N-(2-pyridylmethyl)-N′,N′-diethylethylenediamine (HL³). Single crystal X-ray structure determination of [Re^VO(L¹)Cl(OH₂)]Cl confirms the amido binding of ReO³⁺ species. In the solid state of [Re^VO(L¹)Cl(OH₂)]Cl, the coordinated and counter chloride ions are engaged in Re-Cl…H-C(ring), Cl…H-C(ring) and Re-(OH₂)…Cl hydrogen bonding and forming of a supramolecular network in the solid state. The subunit of the supramolecular network consists of one eight-membered and two nine-membered hydrogen bonded rings. The average diameters of eight-membered and nine-membered rings are ∼3.70 and ∼5.26 Å, respectively.     

Structure and Flexibility of the C-Ring in the Electromotor of Rotary FoF1-ATPase of Pea Chloroplasts

A ring of 8–15 identical c-subunits is essential for ion-translocation by the rotary electromotor of the ubiquitous F_OF₁-ATPase. Here we present the crystal structure at 3.4Å resolution of the c-ring from chloroplasts of a higher plant (Pisum sativum), determined using a native preparation. The crystal structure was found to resemble that of an (ancestral) cyanobacterium. Using elastic network modeling to investigate the ring''s eigen-modes, we found five dominant modes of motion that fell into three classes. They revealed the following deformations of the ring: (I) ellipsoidal, (II) opposite twisting of the luminal circular surface of the ring against the stromal surface, and (III) kinking of the hairpin-shaped monomers in the middle, resulting in bending/stretching of the ring. Extension of the elastic network analysis to rings of different c_n-symmetry revealed the same classes of dominant modes as in P. sativum (c₁₄). We suggest the following functional roles for these classes: The first and third classes of modes affect the interaction of the c-ring with its counterparts in F_O, namely subunits a and bb''. These modes are likely to be involved in ion-translocation and torque generation. The second class of deformation, along with deformations of subunits γ and ε might serve to elastically buffer the torque transmission between F_O and F₁.     

Synthesis and cytotoxic potency of novel tris(1-alkylindol-3-yl)methylium salts: Role of N-alkyl substituents

Novel derivatives of tris(indol-3-yl)methane and tris(indol-3-yl)methylium salts with the alkyl substituents at the N-atoms of the indole rings were synthesized. An easy substitution of indole rings in trisindolylmethanes for other indoles under the action of acids is demonstrated, and the mechanism of substitution is discussed. To obtain trisindolylmethylium salts, the environmentally safe method of oxidation of trisindolylmethanes with air oxygen in acidic conditions was developed. Tris(1-alkylindol-3-yl)methanes and tris(1-alkylindol-3-yl)methylium salts represent three-bladed molecular propellers whose physico-chemical and biological properties strongly depend on the N-alkyl substituent. The cytotoxicity of novel compounds increased with the number of C atoms in the alkyl chains, with optimal number n = 3–5 whereas the derivatives with longer side chains were less cytotoxic. The most potent novel compounds killed human tumor cells at nanomolar-to-submicromolar concentrations, being one order of magnitude more potent than the prototype antibiotic turbomycin A [tris(indol-3-yl)methylium salt]. Apoptosis in HCT116 colon carcinoma cell line induced by tris(1-pentyl-1H-indol-3-yl)methylium methanesulfonate was detectable at concentrations tolerable by normal blood lymphocytes. Thus, N-alkyl substituted tris(1-alkylindol-3-yl)methylium salts emerge as perspective anticancer drug candidates.     

Structural investigations of mode of action of drugs. I. Molecular structure of mitomycin C.

The crystal and molecular structure of the antitumor antibiotic mitomycin C has been determined by X-ray diffraction. The space group is monoclinic P2₁ with cell dimensions $\text{a}\text{=77.988(3)}$, $\text{b}\text{=20.355(7)}$, $\text{c}\text{=9.679(3)}\text{A}\text{?}$, β=95.99°(1) and Z=4. The structure was solved by direct methods. There are two independent molecules per asymmetric unit. The structure was refined to an R value of 0.049 for 2151 observed reflections measured on diffractometer. The benzoquinone ring is slightly deviated from planarity. The N4 in the indole ring behaves like an amide nitrogen owing to its participation in the conjugated benzoquinoid system. The five membered ring through C1, C2, C3, N4 and C9a adopts an envelope conformation. The molecules are held together in crystal by the hydrogen bonds. All nitrogens except N4 are involved in the hydrogen bonding. Studies with models of drug and DNA indicate two different kinds of mechanism for crosslinking.     

Kristall- und molekülstruktur des mono-O-isopropylidenderivatives der dimeren 1,6-anhydro-β-D-arabino-hexopyranos-3-ulose

Acetonation of dimeric 1,6-anhydro-β-D-arabino-hexopyranos-3-ulose yields, besides a monomeric di-O-isopropylidene compound, the dimer 2, which crystallizes in space group P2₁2₁2₁ with a  1.3680 (9), b  1.0686 (7), and c  1.0319 (7) nm, Z  4. The crystal and molecular structure of 2 have been determined by X-ray analysis with direct methods and was refined to a final R_w of 5.55% for 2468 reflections. Compound 2 has not the same dimeric structure as the parent compound with a central 1,4-dioxane ring, but contains instead a central 1,3-dioxolane ring. The pyranose ring bearing the isopropylidene group adopts an almost ideal sofa conformation, with a nearly planar arrangement of C-1, C-2, C-3, C-4, and C-5. By analogy, it was concluded that the dimeric mono-O-isopropylidene derivative 7 of 1,6-anhydro-β-D-xylo-hexopyranos-3-ulose has the same asymmetric structure. The 360-MHz ¹H-n.m.r. spectra of both compounds are in full agreement with the proposed structures.     

Crystal and molecular structure of Δ-cis-α-ethylenebis-S-prolinato(1,2-diamino-ethane)cobalt(III) perchlorate dihydrate, Δ-cis-α-[Co(ss-EBP)(en)] ClO4·2H2O

The crystal and molecular structure of Δ- cis-α- ethylenebis-S-prolinato(1,2-diaminoethane)cobalt(III) perchlorate dihydrate, Δ-cis-α-[Co(SS-EBP)(en)] ClO₄· 2H₂O, was determined from three-dimensional X-ray diffractometer data. The complex crystallizes in the orthorhombic system, space group P2₁2₁2₁ with a = 7.879(4) Å, b = 13.738(9) Å, c = 19.445(2) Å, V = 2104(2) ų. With Z = 4, the observed and calculated densities are 1.60(2) and 1.605 g cm^?3, respectively. The structure was refined by the block- diagonal least-squares technique to a final R = 0.0560 for 1604 observed reflections. The geometry about the cobalt atom is roughly octahedral with the tetradentate SS-EBP (= ethylenebis-S-prolinate ion), assuming cis-α configuration in which the complex possesses two out-of-plane amino acidate (R) rings and the backbone ethylenediamine (E) ring. The E ring conformation is δ. On the other hand, the R rings have λ conformation as well as the en ring. Δ-R_NR_N?(δ_E  λ_R1  λ_R2)(λ_en)-cis-α-[Co(SS-EBP)(en)]⁺ is one of two possible isomers of this compound which have been isolated and whose absolute configurations have been tentatively assigned by spectroscopy. The crystal and molecular structure determination confirms these assignments.     

Crystal Structure and Site-directed Mutagenesis of 3-Ketosteroid Δ1-Dehydrogenase from Rhodococcus erythropolis SQ1 Explain Its Catalytic Mechanism

3-Ketosteroid Δ¹-dehydrogenases are FAD-dependent enzymes that catalyze the 1,2-desaturation of 3-ketosteroid substrates to initiate degradation of the steroid nucleus. Here we report the 2.0 Å resolution crystal structure of the 56-kDa enzyme from Rhodococcus erythropolis SQ1 (Δ¹-KSTD1). The enzyme contains two domains: an FAD-binding domain and a catalytic domain, between which the active site is situated as evidenced by the 2.3 Å resolution structure of Δ¹-KSTD1 in complex with the reaction product 1,4-androstadiene-3,17-dione. The active site contains four key residues: Tyr¹¹⁹, Tyr³¹⁸, Tyr⁴⁸⁷, and Gly⁴⁹¹. Modeling of the substrate 4-androstene-3,17-dione at the position of the product revealed its interactions with these residues and the FAD. The C1 and C2 atoms of the substrate are at reaction distance to the N5 atom of the isoalloxazine ring of FAD and the hydroxyl group of Tyr³¹⁸, respectively, whereas the C3 carbonyl group is at hydrogen bonding distance from the hydroxyl group of Tyr⁴⁸⁷ and the backbone amide of Gly⁴⁹¹. Site-directed mutagenesis of the tyrosines to phenylalanines confirmed their importance for catalysis. The structural features and the kinetic properties of the mutants suggest a catalytic mechanism in which Tyr⁴⁸⁷ and Gly⁴⁹¹ work in tandem to promote keto-enol tautomerization and increase the acidity of the C2 hydrogen atoms of the substrate. With assistance of Tyr¹¹⁹, the general base Tyr³¹⁸ abstracts the axial β-hydrogen from C2 as a proton, whereas the FAD accepts the axial α-hydrogen from the C1 atom of the substrate as a hydride ion.     

Synthesis and characterization of platinum(II) complexes of 2N1O-donor ligands with a pendent indole ring

The Pt(II) complexes of 2N1O-donor ligands containing a pendent indole, 3-[N-2-pyridylmethyl-N-2-hydroxy-3,5-di(tert-butyl)benzylamino]ethylindole (Htbu-iepp), and 1-methyl-3-[N-2-pyridylmethyl-N-2-hydroxy-3,5-di(tert-butyl)benzylamino]ethylindole (Htbu-miepp) (H denotes an ionizable hydrogen), were synthesized, and the structure of [Pt(tbu-iepp)Cl] (1) was determined by X-ray analysis. Complex 1 prepared in CH₃CN was revealed to have the C2 atom of the indole ring bound to Pt(II) with the Pt(II)-C2 distance of 1.981(3) Å. On the other hand, [Pt(tbu-miepp)Cl] (2) was concluded to have a phenolate coordination instead of the C2 atom of the indole ring by ¹H NMR spectra. Reaction of 1 with 1 equiv. of Ce(IV) in DMF gave the corresponding one-electron oxidized species, which exhibited an ESR signal at g = 2.004 and an absorption peak at 567 nm, indicating the formation of the Pt(II)-indole-π-cation radical species. The half-life, t_1/2, of the radical species at −60 °C was calculated to be 43 s (k_obs = 1.6 × 10⁻² s⁻¹).     

Structure of 2-acetamido-3-amino-2,3-dideoxy-d-glucofuranurono-6,3-lactam

An X-ray crystallographic analysis of the title compound, an N-acetyl derivative of the 2,3-diamino-2,3-dideoxy-d-glucofuranurono-6,3-lactam found in the hydrolyzate of Pseudomonas aeruginosa P14 lipopolysaccharide, was performed. The crystals are monoclinic, space group P2₁, a = 11.704(2), b = 5.333(1), c = 7.399(2) Å, β = 91.63(2)°, and Z = 2. The structure was solved by direct methods and refined by the block-diagonal least-squares method to a final R value of 0.046 for 796 independent reflections. The dihedral angle between the mean plane through the furanose ring and that through the γ-lactam ring is 106.2(2)°, the furanose ring is ¹T₂, and the C-3, C-4, C-6, and N-3 atoms of the γ-lactam ring are nearly coplanar. The conformation in aqueous solution is discussed, based on the ¹H-n.m.r. data.     

Biosynthesis of phenylalanine,tyrosine, 3-(3-carboxyphenyl)alanine and 3-(3-carboxy-4-hydroxyphenyl)alanine in higher plants: Examples of the transformation possibilities for chorismic acid

¹⁴C-labelled shikimic acid and double labelled shikimic acid tritiated stereospecifically at C-6 are incorporated into 3-(3-carboxyphenyl)alanine, 3-(3-carboxyl-4-hydroxyphenyl)alanine, phenylalanine, and tyrosine in Resda lutea L., Reseda odoratta L., Iris x Hollandica cv. Prof. Blauw, and Iris x hollandica cv. Wedgwood. The experiments with ¹⁴C-labelled shikimic acid confirm that the aromatic carboxyl groups and rings in 3-(3-carboxyphenyl)-alanine and 3-(3-carboxy-4-hydroxyphenyl)alanine derive from the carboxyl group and ring in shikimic acid whereas the experiments with double labelled shikimic acid demonstrate that the pro-6S-hydrogen atom is retained and the pro-6R-hydrogen atom lost in the biosynthesis of 3-(3-carboxyphenyl)alanine, phenylalanine, and tyrosine in the plants used. ³H was located in the ortho-position in the aromatic rings of phenylalanine and tyrosine but in a position para to the alanine side chain of 3-(3-cabroxyphenyl)alanine. No ³H was found in 3-(3-carboxy-4-hydroxyphenyl)alanine. This supports a derivation of the last two compounds from chorismic acidvia isochorismic acid, isoprephenic acid, and 3′-carboxyphenylpyruvic acid and 3′-carboxy-4′-hydroxyphenylpyruvic acid. The ³H/¹⁴ C ratio in 3-(3-carboxyphenyl)alanine was found higher than in the precursor used. This isotope effect must operate by competition between the pathways from isoprephenic acid to 3′-carboxyphenylpyruvic acid and to 3′-carboxy-4′-hydroxyphenylpyruvic acid. The proposed biosynthetic pathways for the two carboxy-substituted amino acids are in agreement with their distribution patterns in the plant kingdom and suggest that they may derive from minor changes of enzymes involved in the general pathways of aromatic biosynthesis.     

Molecular structures of electron-transfer active complexes [Re(XQ)(CO)3(NN)] (XQ=N-Me-4,4-bipyridinium or N-Ph-4,4-bipyridinium; NN=bpy, 4,4-Me2-2,2-bpy or N,N-bis-isopropyl-1,4-diazabutadiene) in the solid state and solution: an X-ray and NOESY NMR study

Crystal and molecular structures of a series of complexes [Re(XQ⁺)(CO)₃(NN)]²⁺ (XQ=N-methyl-4,4^′-bipyridinium (MQ⁺) and N-phenyl-4,4^′-bipyridinium (PQ⁺) and NN=bpy, 4,4^′-dimethyl-bpy (dmb) or N,N^′-bis-isopropyl-1,4-diazabutadiene (ⁱPr-DAB)) in the solid state have been determined by X-ray diffraction. Aromatic rings within the XQ⁺ ligand were found to be highly staggered. The dihedral angles between the pyridine and pyridinium rings were found in the range 39°-45° for MQ⁺ and 28°-46° for PQ⁺. The exceptionally low dihedral angle of 8° in [Re(MQ⁺)(CO)₃(dmb)]²⁺ is due to crystal-packing effects. The pyridinium and phenyl rings of the PQ⁺ ligand are even more staggered, with dihedral angles in the range 40°-55°. The pyridine ring of the XQ⁺ ligand is oriented relative to the equatorial ligands in such a way that it bisects the angles between the equatorial Re-N and Re-C bonds in all complexes, except for [Re(PQ⁺)(CO)₃(ⁱPr-DAB)](PF₆)₂, where it bisects the DAB ligand. Structures of the complexes [Re(XQ⁺)(CO)₃(NN)]²⁺ (NN=bpy, dmb) were also studied in solution using NOESY NMR. It was found that the orientation of the XQ⁺ ligand relative to the equatorial ligands is the same as in the solid state. The XQ⁺ ligands become even more staggered on going to the solution where pyridine-pyridinium dihedral angles range from 42° to 45°. A value of ∼69° was found for the pyridinium-phenyl dihedral angle in PQ⁺ complexes. The structural data obtained are related to electron-transfer activity of XQ⁺ complexes. It follows that any ground- or excited-state electron transfer reactions or optical charge transfer excitation have to be coupled with a major reorganization of the XQ⁺ ligand, namely twisting of its aromatic rings and shortening of the interring C-C bond. This conclusion has important implications for estimates of Marcus inner reorganization energy and electron transfer dynamics.     

One-dimensional Cd metal string complex: Synthesis,structural and thermal properties of [(HPy)3(Cd3Cl9)]∞

The cadmium metal string complex of [(HPy)₃(Cd₃Cl₉)]_∞ (Py = pyridine) was prepared. Its structural and thermal properties were also investigated. Its existing form in gas phase has been elucidated by density functional calculations. The crystal structure consists of protonation pyridine cations and infinite one-dimensional chains of [Cd₃Cl₉]³⁻ anions. Each Cd atom is octahedrally surround by bridged chlorine atoms, giving rise to polymeric chain along the a-axis. The pyridinium lie in the middle of the chain to balance the charge. The DFT study indicates that the HOMO orbital of optimized structure is mainly localized on the middle six chloride ions and the LUMO is delocalized. Differential thermal gravimetric analysis shows there is no presence of any structural phase transitions.     

Synthesis and evaluation of N(1)-alkylindole-3-ylalkylammonium compounds as nicotinic acetylcholine receptor ligands

In this study thirty-three novel indole derivatives were designed and synthesized based on the structure of deformylflustrabromine B (1), a metabolite isolated from the marine bryozoan Flustra foliacea L. The syntheses were carried out using standard methodologies and in good yields. The molecules were tested for their affinities for the α4β2¹, α3β4¹, α7¹ and (α1)₂β1γδ nicotinic acetylcholine receptor (nAChR) subtypes. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with K_i = 136.1, 93.9 and 862.4 nM for the α4β2¹, α3β4¹, and α7¹ nAChRs subtypes, respectively. These results indicated that the indole core might be a useful scaffold for the development of new potent and selective nAChR ligands.     

Phase relationships in the uranium-palladium-sulfur system. II. Characterisation and crystal structure of UxPd3S4 (0.9 < x < 1)

The new ternary uranium-palladium-sulfide U_xPd₃S₄ (0.9<x<1) crystallizes in the cubic system a =6.639(2) Å, space group Pm₃n, with a platinum bronze type structure. Refinement of the structure of a single crystal grown by the chemical vapour transport method revealed an incomplete uranium site filling in the crystal lattice, corresponding to the formula: U_o.92Pd₃S₄. The crystal radius of the uranium is found to be intermediate between U³⁺ and U⁴⁺. so that the uranium is expected to be in an intermediate valence state.