Hydrogen bonding patterns in the cocrystals of 5-nitrouracil with several donor and acceptor molecules

Cocrystals of 5-nitrouracil with solvent molecules, dioxane, pyridine, DMSO, formamide and ethanol as well as with piperazine, N, N'-dimethylpiperazine, 3-aminopyridine and diazabicyclo [2.2.2]octane obtained by deliberate inclusion, have been examined by X-ray crystallography. The tape structure found in the parent centric form of nitrouracil is retained with some modifications in the cocrystals with dioxane, piperazine, diazabicyclo [2.2.2]octane, N,N'-dimethylpiperazine, pyridine and DMSO, with the guest molecules forming alternate tapes. In cocrystals involving formamide, ethanol and 3-aminopyridine, the molecular tapes exhibit mixed compositions. The observed bonding patterns have been classified into six schemes. Interestingly, quadruple type hydrogen bonding patterns are seen in cocrystals containing 3-aminopyridine or ethanol and water, while a network of acyclic tetrahedral pentamers of water is found in the cocrystal containing diazabicyclo [2.2.2]octane and water

A charge density study of an intramolecular charge-transfer quinoid compound with strong NLO properties

An experimental charge density investigation of 7,7-di[(S)-(+)-2-(methoxymethyl)pyrrolidino]-8,8-dicyanoquinodimethane establishes the presence of a large charge separation as well as a high in-crystal dipole moment compared to the free molecule in frozen geometry, consistent with the high SHG activity of the compound

Structure of cholest-5-en-3β-oxy-5-bromopentane by single-crystal X-ray diffraction at 130 K

Cholest-5-en-3β-oxy-5-bromopentane (1) and cholest-5-en-3β-oxy-11-bromoundecane (2), key precursors for the synthesis of novel cationic amphiphiles based on cholesterol, have been synthesized and characterized by 1H-NMR spectroscopy and X-ray crystallography. Thermal disorder and effect of length of the bromoalkyl segment on the crystal structure have been investigated. Possible molecular level explanation of the unusual alternating s-trans-gauche conformation of the bromopentyl side chain of (1) has been presented

An experimental charge density study of the effect of the noncentric crystal field on the molecular properties of organic NLO materials

The structure, packing, and charge distribution in molecules of nonlinear optical materials have been analysed with reference to their counterparts in centrosymmetric structures based on low temperature X-ray measurements. The systems studied are the centric and noncentric polymorphs of 5-nitrouracil as well as the diamino, dithio, and thioamino derivatives of 1,1-ethylenedicarbonitrile; the latter possesses a noncentric structure. The molecular structure of 5-nitrouracil is invariant between the two forms, while the crystal packing is considerably different, leading to dimeric N-H···O rings in the centric polymorph and linear chains in noncentric one. There is an additional C-H···O contact in the centric form with a significant overlap of the electrostatic potentials between the alkenyl hydrogen atom and an oxygen atom of the nitro group. The dipole moment of 5-nitrouracil in the noncentric form is much higher (μ=9 D) than in the centric form (≈6 D). Among the 1,1-ethylenedicarbonitriles, there is an increased charge separation in the noncentric thioamino derivative, leading to an enhanced dipole of 15 D compared to the centric diamino (5 D) and dithio (6 D) derivatives. The effect of the crystal field is borne out by semiempirical AM1 calculations on the two systems. Dipole moments calculated for the molecules in the frozen geometries match closely with those obtained for centric crystals from the experimental charge densities. The calculated values of the dipole moment in the frozen or optimized geometries in the noncentric structures are, however, considerably lower than the observed value. Furthermore, the conformation of the S-CH3 group in the noncentric crystal is anti with respect to the central C=C bond while the syn conformation is predicted for the free molecule in the optimized geometry

Targeting Glycosylation Pathways and the Cell Cycle: Sugar-Dependent Activity of Butyrate-Carbohydrate Cancer Prodrugs

SummaryShort-chain fatty acid (SCFA)-carbohydrate hybrid molecules that target both histone deacetylation and glycosylation pathways to achieve sugar-dependent activity against cancer cells are described in this article. Specifically, n-butyrate esters of N-acetyl-d-mannosamine (But4ManNAc, 1) induced apoptosis, whereas corresponding N-acetyl-d-glucosamine (But4GlcNAc, 2), d-mannose (But5Man, 3), or glycerol (tributryin, 4) derivatives only provided transient cell cycle arrest. Western blots, reporter gene assays, and cell cycle analysis established that n-butyrate, when delivered to cells via any carbohydrate scaffold, functioned as a histone deacetylase inhibitor (HDACi), upregulated p21WAF1/Cip1 expression, and inhibited proliferation. However, only 1, a compound that primed sialic acid biosynthesis and modulated the expression of a different set of genes compared to 3, ultimately killed the cells. These results demonstrate that the biological activity of butyrate can be tuned by sugars to improve its anticancer properties

Detailed Molecular and Immune Marker Profiling of Archival Prostate Cancer Samples Reveals an Inverse Association between TMPRSS2:ERG Fusion Status and Immune Cell Infiltration

Prostate cancer is a significant global health issue and limitations to current patient management pathways often result in over- or under-treatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow utilizing an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA-Seq, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA-seq in 27/27 cases and a significantly higher TIL count was noted in tumors without a TMPRSS2:ERG fusion compared to those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n=436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-High and TIL-Low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1/27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion positive tumors. Detailed profiling, as shown here, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort

A Mn K-EXAFS study of Y_0.5Ca_0.5MnO₃

Mn K-EXAFS measurements of Y0.5Ca0.5MnO3 from 300 K to 120 K show a large static disorder around 160 K, besides significant distortion of the MnO6 octahedron. The average Debye-Waller factor for the MnO octahedral coordination is 0.0025 Å2 in the 160 K region while it is somewhat lower (0.001 Å2) above and below 160 K. These observations are discussed in the light of the structural data as well as the electrical and magnetic properties of this solid

Synthesis, structure, spectra and redox behaviour of copper(II) complexes of certain bis(phenolate) ligands: Phenoxyl radical complexes of copper(II) as models for galactose oxidase

2210-2222Copper(II) complexes of a series of tetradentate tripodal and linear ligands containing two substituted phenolates appended to N,N-dimethylethylenediamine and N,N' dimethylethylenediamine moieties viz. N,N-dimethyl-N',N'-bis(2-hydrox y-4-nitrobenzyl)ethylenediamine [H2(L1)], N ,N-dimethyl-N',N' -bis(2-hydroxy-3 ,5-dimethylbenzyl)ethylenediamine [H2(L2)], N,N-dimethyl-N',N'- bis(2-hydroxy-3 ,5-di-tert-butylbenzyl)ethylenediamine [H2(L3)], N,N'-dimelhyl-N,N'-bis(2-hydrox y-4-nitrobenzyl)ethylenediamine [H2(L4 )l, N ,N'-dimelhyl-N ,N' -bis(2-hydroxy-3,5-dimethylbe nzyl)ethylenediamine [H2(L5)] and N,N'-dimelhyl-N,N'-bis(2-hydroxy-3,5-di-tert-butylbenzyl)ethylenediamine [H2(L6)] have been isolated and characterized by electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes, [Cu(L1)]2.2H2O 1, [Cu(L1)(py)] 1a and [Cu(L4)(H2O)].H2O 4 have been structurall y characterized by X-ray crystallography. The coordination structure of 1 is dimeric with a trigonal bipyramidal distorted square based pyramidal geometry (TBOSBP) around each Cu(II). In complex 1a also a trigonal bipyramidal distorted square based pymmid;]1 geometry (TBDSBP) around Cu(II) is present. The Cu2O2 basal plane is comprised two phenolates and a tertiary amine nitrogen of H2(L1) and an exogenous pyridine nitrogen and the dimethyl substituted amine nitrogen of H2(L1) is axially coordinated. In 4, there are two different copper(II) complex molecules in the same unit cell with trigonal bipyramidal distorted square based pyramidal geometry (TBDSBP) around Cu(II). The methyl groups of the ethylenediamine frame are cis to each other in one molecule (A) and are trans to each other in the other molecule (B). The bond lengths and bond angles in the two molecules are different. The ligand field and EPR spectra of all the complexes are consistent with a squarebased geometry even in solution. An intense band observed in the range 390-465 nm may originate from Cu(II) →(phenolate)O-(axial) and/or equatori al(phenolate)O- → Cu(II) CT transitions. The gǁ values lie in the range 2.23-2.29 indicating the presence of CuN2O2 or CuNO3 chromophores. All the complexes show an irreversible CuII/CuI redox process at increased negative E1/2 values, which are consistent with the presence of two coordinated phenolate groups. The oxidation wave(s) occurring in the range 0.06-0.89 V (vs Ag/Ag+) demonstrate(s) the formation of phenoxyl radical-copper(II) species. The influence of the phenolate substituents on the PhO- → Cu(II) LMCT transition and the Cu(II)-phenolate/Cu(II)phenoxyl radical redox potentials are discussed. The stability of the radicals is enhanced with the increase in donor ability of the substituents. The relevance of the notable structural and spectral features of the complexes containing two redox active phenolates bound to copper(II) in a square pyramidal environment, to those of galactose and glyoxal oxidases are highlighted

Copper(II) complexes of sterically hindered phenolate ligands as structural models for the active site in galactose oxidase and glyoxal oxidase: x-ray crystal structure and spectral and redox properties

Copper(II) complexes of a series of tripodal ligands containing a phenolate moiety, viz. 2-(bis(1-methylbenzimidazol-2-yl)aminomethyl)-4-nitrophenol [H(L1)] and N,N-dimethyl-N'-(pyrid-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)-ethylenediamine [HL2] have been isolated and characterised by electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. The X-ray crystal structure of the binuclear perchlorate complex [Cu(L2)]2(ClO4)2 reveals a square based pyramidal distorted trigonal bipyramidal (SBPDTB) coordination geometry around Cu(II). The CuN2O trigonal coordination plane is comprised of N,N-dimethyl substituted amine nitrogen, one pyridyl nitrogen and a phenolate oxygen of the ligand. The axial positions are occupied by the tertiary amine nitrogen and the phenolate ion from the second coordination sphere resulting in the dimerisation. The ligand field and EPR spectra of all the complexes are consistent with a square-based geometry in solution. An intense band observed around 390 nm may originate from Cu(II) → O- (phenolate, axial) and/or equatorial (phenolate) O- → Cu(II) CT transitions. The g|| values lie in the range 2.24-2.28 indicating the presence of CuN2O2 or CuN3O chromophores. The incorporation of sterically hindered N,N-dimethyl substituted nitrogen and bulky 1-methylbenzimidazole groups tends to enhance the trigonal distortion and raise the Cu(II)/Cu(I) redox potential

An investigation of the photo-reactive and unreactive polymorphs of o-ethoxy cinnamic acid and of its photodimer

Detailed X-ray crystallographic investigation of the reactive α- and the unreactive γ-polymorphs of o-ethoxy cinnamic acid has been carried out along with that of the photodimer, α-truxillic acid. The molecule is quite planar in the α-form, but in the γ-form, the side groups deviate significantly from the plane of the benzene ring. The carboxylic groups form normal cyclic hydrogen bonds in the a-form and near-symmetric hydrogen bonds in the γ-form. The infrared spectrum of the a-form shows the characteristic features of the cyclic dimer, but that of the γ-form is entirely different, marked by the absence of the O–H stretching band in the 3000cm^–1 region. Charge density analysis throws some light on the structure and reactivity of the molecule in the two forms. The near-symmetric hydrogen bond in the γ-form is ionic and appears to restrict conjugation by way of distorting the molecule. This unusual feature keeps the cinnamoyl double bonds away from each other, rendering it photochemically unreactive. In the α-form, however, the double bonds have a closer approach. The cyclobutyl ring of the photodimer consists of weak single bonds, with the new pair being slightly longer