Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C₁₉H₂₅NO₃) a Molecule with Antiproliferative Activity

The single crystal X-ray structure of the novel steroid derivative, 6E-hydroximino-androst-4-ene-3,17-dione ( C19H25NO3) (code name RB-499), possessing antiproliferative activity against various cell lines is presented. The analysis produced the following results: chemical formula C19H25NO3; Mr = 315.40; crystals are orthorhombic space group P212121 with Z = 4 molecules per unit cell with a = 6.2609(2), b = 12.5711(4), c = 20.0517(4) Å,Vc = 1578.18(7) Å3, crystal density Dc = 1.327 g/cm³. Structure determination was performed by direct methods, Fourier and full-matrix least-squares refinement. Hydrogens were located in the electron density and refined in position with isotropic thermal parameters. The final R-index was 0.0324for 3140 reflections with I > 2σ and 308 parameters. The Absolute Structure Parameter − 0.07(5) confirms the correct allocation of the absolute configuration. The presence of the double bond C=O at position 3 in Ring A has caused a distortion from the usual chair conformation and created an unusual distorted sofa conformation folded across an approximate m-plane through C(1)–C(4). Ring B is a distorted chair, its conformation being influenced by the presence of the C(6)=N(6)–O(6)H group in position 6. Ring C is a symmetrical chair. Ring D exhibits both a distorted mirror symmetry conformation [influenced by the C(17)=O(17) group] and a distorted twofold conformation. DFT calculations indicated some degree of flexibility in rings A, C and D with ring A showing the greatest variation in torsion angles. The crystal packing is governed by H-bonds involving O(3), O(6) and O(17). DFT calculations of bond distances and angles, optimized at the B3LYP/6–31++G(d,p) level, were in good agreement with the X-ray structure

Ultra-high resolution X-ray structures of two forms of human recombinant insulin at 100 K

The crystal structure of a commercially available form of human recombinant (HR) insulin, Insugen (I), used in the treatment of diabetes has been determined to 0.92 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16,000 keV (λ = 0.77 Å). Refinement carried out with anisotropic displacement parameters, removal of main-chain stereochemical restraints, inclusion of H atoms in calculated positions, and 220 water molecules, converged to a final value of R = 0.1112 and Rfree = 0.1466. The structure includes what is thought to be an ordered propanol molecule (POL) only in chain D(4) and a solvated acetate molecule (ACT) coordinated to the Zn atom only in chain B(2). Possible origins and consequences of the propanol and acetate molecules are discussed. Three types of amino acid representation in the electron density are examined in detail: (i) sharp with very clearly resolved features; (ii) well resolved but clearly divided into two conformations which are well behaved in the refinement, both having high quality geometry; (iii) poor density and difficult or impossible to model. An example of type (ii) is observed for the intra-chain disulphide bridge in chain C(3) between Sγ6–Sγ11 which has two clear conformations with relative refined occupancies of 0.8 and 0.2, respectively. In contrast the corresponding S–S bridge in chain A(1) shows one clearly defined conformation. A molecular dynamics study has provided a rational explanation of this difference between chains A and C. More generally, differences in the electron density features between corresponding residues in chains A and C and chains B and D is a common observation in the Insugen (I) structure and these effects are discussed in detail. The crystal structure, also at 0.92 Å and 100 K, of a second commercially available form of human recombinant insulin, Intergen (II), deposited in the Protein Data Bank as 3W7Y which remains otherwise unpublished is compared here with the Insugen (I) structure. In the Intergen (II) structure there is no solvated propanol or acetate molecule. The electron density of Intergen (II), however, does also exhibit the three types of amino acid representations as in Insugen (I). These effects do not necessarily correspond between chains A and C or chains B and D in Intergen (II), or between corresponding residues in Insugen (I). The results of this comparison are reported

Crystallization and preliminary X-ray analysis of the DNA decamers d(CCGGATCCGG) and d(CCGGCGCCGG)

The DNA decamers d(CCGGATCCGG) and d(CCGGCGCCGG) have been crystallized for X-ray analysis in order to investigate the effects of changing the two central base pairs of the DNA fragment d(CCGGGACCGG). Previous studies have already demonstrated that the structure of the former DNA fragment contains a DNA Holliday junction. Crystals were obtained at 293 K by the hanging-drop vapour-diffusion technique using the Nucleic Acid Mini Screen. Over a period of two weeks, hexagonal plates appeared. For the DNA fragment d(CCGGATCCGG), the crystals belong to space group P31, with unit-cell parameters a = b = 33.54, c = 46.39 Å, α = β = 90, γ = 120°, and diffract to 2.2 Å. In the case of the DNA fragment d(CCGGCGCCGG) the crystals belong to the space group C2, with unit-cell parameters a = 65.35, b = 24.07, c = 37.34 Å, β = 109.97°, and diffract to 2.0 ÅPeer Reviewe

Crystallization and preliminary X-ray analysis of the antimalarial and cytotoxic alkaloid cryptolepine complexed with the DNA fragment d(CCTAGG)2

Crystals of the indoloquinoline alkaloid cryptolepine complexed with the DNA fragment d(CCTAGG)2 have been grown by the hanging-drop technique at 293 K using ammonium sulfate as the precipitating agent. Over a period of three weeks, yellow tapering bullet-shaped crystals grew to maximum dimensions of 0.2 × 0.1 × 0.1 mm. The crystals belong to space group P64, with unit-cell parameters a = b = 29.960, c = 39.64 Å, α = β = 90, γ = 120°, and diffract to 1.4 Å.Peer Reviewe

X-ray and neutron structure of 1,8-(3,6,9-trioxaundecane-1,11-diyldioxy)-9,10-dihydro-10,10-dimethylanthracene- 9-ol (p326); some pitfalls of automatic data collection

The structure of the crown ether 1,8-(3,6,9-trioxaundecane-1,11-diyldioxy)-9,10-dihydro-10,10-dimethylanthracene-9-ol, C24H30O6·H2O (1), code name P326, the parent compound for a series of derivatives, has been determined by both X-ray diffraction at room temperature and neutron diffraction at very low temperature. The unit cells are very similar at both temperatures and in both cases the crystals exhibit P21 symmetry with Z = 4 (two molecules, A and B, respectively, per asymmetric unit) and pseudosymmetry P21/c. The higher symmetry is broken mainly by the two independent water molecules in the unit cell, some reflections which would be absent in P21/c having strong intensities in both the X-ray and neutron data. In both molecules A and B hydrogen bonds involving the water molecule stabilize the macrocyclic ring structure, one involving the macrocyclic O(9) as a donor. Close contacts between the water and macrocyclic O atoms in each molecule also suggest the presence of two bifurcated hydrogen bonds, involving water HW2 to both O(16) and O(18), and water HW1 to both O(18) and O(20), respectively, with considerable variation in the geometry being present. Both molecules A and B exhibit very close pseudosymmetry across a plane perpendicular to the molecular plane and through atoms C(9) and O(18), and in addition are predominantly planar structures. The X-ray analysis failed to reveal one H atom per water molecule, each being subsequently included after location and refinement in the neutron analysis.</jats:p