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  • br S Bjelogrli et al br were

    2019-10-18


    S. Bjelogrlić et al.
    were obtained after slow AMG 925 of the solvent at the room tem-perature after three days. The crystals were filtered off and washed with cold ethanol and diethyl ether. Yield: 0.28 g (58%). Anal. Calcd. for
    2.3. Crystal structure determination
    Diffraction data were collected on a Gemini S diffractometer (Oxford Diffraction), equipped with a Mo Kα radiation source (λ = 0.71073 Å)
    and a Sapphire CCD detector. Data collection strategy calculation and data reduction were performed with the CrysAlisPro [90]. Structure was solved by SHELXT [91], and refined with the SHELXL-2014 [92]. The SHELXLE [93] was used as a graphical user interface for the refinement procedures. All non‑hydrogen atoms were refined anisotropically. The
    hydrogen atoms attached to C atoms were placed at geometrically idealized positions with C-H distances fixed to 0.93 and 0.96 Å for sp2
    and sp3 C atoms, respectively. Their isotropic displacement parameters were set equal to 1.2 and 1.5 Ueq of the parent sp2 and sp3 C atoms, respectively. The hydrogen atoms attached to N atoms were located in difference Fourier map and refined isotopically. Structures were vali-dated with PLATON [94] together with extensive use of Mercury CSD 2017 [95] and Cambridge Crystallographic Database (CSD) [96].
    A summary of the crystallographic data for crystal structure is given in Table 1. CCDC 1831819 contains the Supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac. uk/structures/. Calculation of intermolecular interaction energies were performed by using CE-HF model energies [97] embodied in CrystalExplorer17
    Table 1
    Crystallographic and refinement details for 1.
    [98]. Prior to calculations, the lengths of X–H bonds were normalized to standard neutron diffraction values. A Hirshfeld surface [99] was cal-culated for a molecule in the crystal structure, and the number of sur-face patches was determined to be 18, thus defining the coordination number of a molecule. Calculations were performed for all 18 mole-cular pairs comprising of the central molecule and one neighboring molecule.
    2.4. Evaluation of biological activity and computational studies
    Detailed protocols for anticancer related experiments (Annexin V and propidium iodide staining, calculation of ApoC50 concentration, cell cycle analysis, inhibition of caspase activity, evaluation of caspase-8 and -9 activities, determination of mitochondrial superoxide gen-eration, assessment of changes in mitochondrial potential and growth inhibition of 3D tumor models), DNA binding experiments (agarose gel electrophoresis and fluorescence measurements), human serum al-bumin (HSA) interaction experiments, acute lethality assay, as well as details regarding computational studies can be found in Supplementary material.
    3. Results and discussion
    3.1. Synthesis and characterization of 1
    In our previous work complexes with ligands based on haOEt × HCl and N‑heteroaromatic carbonyl compounds were obtained by template reactions involving corresponding metal salts [73–79,100,101]. It was found that reactive ethyl-ester group can undergo hydrolysis [100,101] or trans-esterification reaction and that this processes can be directed by the solvent used for metal complex preparation [79]. Previously, we have obtained the Cd(II) complexes with aphaOEt ligand (Scheme 1A), which represents a condensation product of haOEt × HCl and 2‑ap, by using EtOH as a solvent [76,100]. In this work a novel Cd(II) complex with methyl-ester analogue of aphaOEt, i.e. aphaOMe ligand (Scheme 1A), was prepared by template reaction of Cd(AcO)2 × 2H2O, 2‑ap and haOEt × HCl in MeOH (Scheme 1B).