title: Impact of structural differences in carcinopreventive agents indole-3-carbinol and 3,3'-diindolylmethane on biological activity. An X-ray, ¹H-¹⁴N NQDR, ¹³C CP/MAS NMR, and periodic hybrid DFT study.
abstract: Three experimental techniques (1)H-(14)N NQDR, (13)C CP/MAS NMR and X-ray and Density Functional Theory (GGA/BLYP with PBC) and Hirshfeld surfaces were applied for the structure-activity oriented studies of two phyto-antioxidants and anticarcinogens: indole-3-carbinol, I3C, and 3,3'-diindolylmethane, DIM, (its bioactive metabolite). One set of (14)N NQR frequencies for DIM (2.310, 2.200 and 0.110 MHz at 295K) and I3C (2.315, 1.985 and 0.330 MHz at 160K) was recorded. The multiplicity of NQR lines recorded at RT revealed high symmetry (chemical and physical equivalence) of both methyl indazole rings of DIM. Carbonyl (13)C CSA tensor components were calculated from the (13)C CP/MAS solid state NMR spectrum of I3C recorded under fast and slow spinning. At room temperature the crystal structure of I3C is orthorhombic: space group Pca21, Z=4, a=5.78922(16), b=15.6434(7) and c=8.4405(2)Å. The I3C molecules are aggregated into ribbons stacked along [001]. The oxygen atomsare disorderedbetween the two sites of different occupancy factors. It implies that the crystal is built of about 70% trans and 30% gauche conformers, and apart from the weak OH⋯O hydrogen bonds (O⋯O=3.106Å) the formation of alternative O'H⋯O bonds (O'⋯O=2.785Å) is possible within the 1D ribbons. The adjacent ribbons are further stabilised by O'H⋯O bonds (O'⋯O=2.951Å). The analysis of spectra and intermolecular interactions pattern by experimental techniques was supported by solid (periodic) DFT calculations. The knowledge of the topology and competition of the interactions in crystalline state shed some light on the preferred conformations of CH2OH in I3C and steric hindrance of methyl indole rings in DIM. A comparison of the local environment in gas phase and solid permitted drawing some conclusions on the nature of the interactions required for effective processes of recognition and binding of a given anticarcinogen to the protein or nucleic acid.
authors.affiliation: Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland. Electronic address: Jolanta.Latosinska@amu.edu.pl.
authors.forename: Jolanta Natalia
authors.initials: JN
authors.lastname: Latosińska
authors.affiliation: Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Latosińska
authors.affiliation: Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Szafrański
authors.affiliation: Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, 1000 Ljubljana, Slovenia; "Jozef Stefan" Institute, Jamova 39, 1000 Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Seliger
authors.affiliation: "Jozef Stefan" Institute, Jamova 39, 1000 Ljubljana, Slovenia.
authors.forename: Veselko
authors.initials: V
authors.lastname: Žagar
authors.affiliation: Department of Paediatric Dentistry, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznań, Poland.
authors.forename: Dorota V
authors.initials: DV
authors.lastname: Burchardt
mesh_terms: D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D018360:Crystallography, X-Ray; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure
chemical_list: D016588:Anticarcinogenic Agents; D007211:Indoles; C016517:indole-3-carbinol; C016392:3,3'-diindolylmethane
keywords: Crystalline structure; Disordered structure; Hydroxyl group disorder; Indole-3-carbinol; Topology of interactions