key: cord-1005998-enbdppkw authors: Vaz, Wesley F.; Michelini, Lidiane J.; Oliveira, Gerlon A.R.; Lião, Luciano M.; Perez, Caridad N.; Oliver, Allen G.; Napolitano, Hamilton B. title: Structural comparison of five new halogenated dihydroquinoline-4(1H)-ones date: 2020-06-02 journal: J Mol Struct DOI: 10.1016/j.molstruc.2020.128559 sha: da277ebd3940c5267d7c08ddc3704fd0c7e646bc doc_id: 1005998 cord_uid: enbdppkw Compounds with dihydroquinoline-4(1H)-one nuclei have been reported in the literature for being important in the development of medicines due to their broad spectrum of activities. In this way, the structural knowledge of this class becomes relevant for obtaining new materials with desired biological properties. This study presents the structural elucidation of five halogenated dihydroquinolines, as well as the discussion about the effect on the molecular conformation of the type and position of halogen atom on aromatic rings. Compounds I and IV differ in halogen substitution on 2-phenyl ring, while compounds III and V differ in halogen substitution on the benzylidene ring. Moreover, compound II has a para-substituted 2-phenyl ring in their molecular structure. The crystal packing of all five molecules is mainly ruled by C–H⋯O and C–H···halogen interactions that form dimers and chains. The shift in position and the kind of the halogen in ring C shows a starring role in the conformation of the studied compounds, and the packaging of these compounds is more susceptible to variations when the halogen position changes. Quinolines are a class of N-heterocyclic compounds, also known as benzopyridines, 37 obtained both from natural and synthetic sources. They have attracted great attention in the 38 scientific community being used in several industrial processes, becoming increasingly 39 important in the development of medicines, pesticides and also due to their notable biological 40 activities [1] [2] [3] . Among the compounds of this class, we are interested in those with the 41 dihydroquinoline-4(1H)-one moiety; in this way, the recent studies conducted by our research 42 group involve structural elucidation [4-6], anti-cancer properties [7, 8] and their potential 43 application as pesticides [9] . Also, other groups have explored the cytotoxic properties of this 44 class [10] [11] [12] [13] and as potential Middle East respiratory syndrome coronavirus (MERS-CoV) 45 inhibitors [14] . 46 The biological activity of a substance is dominated by its properties, which are 47 determined by its chemical structure. The structural elucidation is essential since it allows [21] . Data collection and structure refinement details are summarized in Table 2 . The structures I to V were deposited in the Cambridge Crystallographic Data Centre (CCDC) 102 with the code number 1994320, 1994319, 1994318, 1994317, and 1994316, respectively. compounds and chlorine on the latter two compounds. This kind of strategy allowed a 138 complete assignment of the 1 H and 13 C nuclei (see S.I.), and agrees with our previous report Table 3 ). These variances were measured using the following parameters: the 153 torsion angles: C2-C10-C11-C12 (φ 1 ), C2-C1-C17-C22 (φ 2 ) and N1-S1-C23-C28 (φ 3 ), and 154 the dihedral angle between the planes formed by ring A and ring B (∠AB) ( Table 3) . φ1 = C2-C10-C11-C12; φ2 = C2-C1-C17-C22; φ3 = N1-S1-C23-C28. The ∠AB dihedral angle is ca 8⁰ larger in Ib than in Ia, evidencing that the rings in as IIIa and IIIb (Fig. 3) . The overlay of these structures indicates a difference of 14⁰ in 189 ∠AB angle for IIIa and IIIb (Fig. S49) . When compounds I, II and III are compared (∠AB The crystal structure of these chlorine dihydroquinolinones is stabilized by C-H···O 205 and C-H···halogen hydrogen bonds listed in Table 4 . Although these interactions are weak, interaction grows the packing along to the c axis. (Fig. 6) . were labeled as IVa, IVb and IVc (Fig. 7) . As listed in Table 5 , these three structures present φ1 = C2-C10-C11-C12; φ2 = C2-C1-C17-C22; φ3 = N1-S1-C23-C28. Compound V is like compound IV but has an ortho-bromobenzene attached to C1 260 atom. The three independent molecules in the ASU were labeled as Va, Vb and Vc (Fig. 8) . These molecules present a variation of 18⁰ in their ∠AB angle being the descending order 262 equal to Va, Vc and Vb (Fig. S51) . When ∠AB angle values for all fluorine 263 dihydroquinolinones are compared, it is observed a decreasing order Va, IVb, Vc, IVa, IVc, 264 and Vb (Table 5) Displacement ellipsoids are drawn at the 50% probability level and H atoms have been omitted. The molecular packing in the unit cell of compound IV and V is stabilized by C- H···O and C-H···halogen hydrogen bonds (Table 6 ). In compound IV, the contacts C5B- formed by the following interactions: C8A-H8A···F1B and C7A-H7A···O1B (Fig.10) . The interaction C18-H18···O2, and C18A-H18A···O2A create two independent ‫ܥ‬ ଵ ଵ ሺ7ሻ 304 chains while C24A-H24A···O1A create a ‫ܥ‬ ଵ ଵ ሺ9ሻ chain, along to c axis. In the same orientation to these chains there is one more ‫ܥ‬ ଵ ଵ ሺ7ሻ arrangement formed by C18B-306 H18B···O2B interaction. This chain connects to others along to a axis, via C26A-307 H26A···O1B and C27B-H27B···O1A interactions (Fig.10) . for I and 19⁰ for IV). The torsion angle φ 3 in IV is larger than I (10⁰ and 19⁰, respectively). 324 Regarding molecular packing, the chlorine compound forms ‫ܥ‬ ଵ ଵ ሺ7ሻ and ‫ܥ‬ ଵ ଵ ሺ6ሻ chains, while the 325 fluorine compound forms ‫ܥ‬ ଵ ଵ ሺ7ሻ chains. All those chains grow along the a axis. Finally, discrete 326 contacts join these chains along the b and c axis. 327 In contrast, compounds III and V differ in the halogen in the ortho position of ring B, 328 chlorine, and fluorine, respectively. In terms of ∠AB values, the decreasing order is Va, Vc, IIIb, 329 IIIa, and Vb. The torsion φ 1 in III is smaller than V (1⁰ and 13⁰, respectively). Regarding the 330 torsion φ 2, both compounds present similar values (17⁰ in III and 14⁰ in V). Moreover, the torsion 331 φ 3 to III is larger than V (17⁰ and 10⁰, respectively). These small alterations occur likely due to the 332 change in radius of the halogen atoms. In terms of molecular packing both compounds have ܴ ଶ ଶ ሺ12ሻ 333 dimers but in III it is related to SO 2 group while in the compound V it is related do the carbonyl 334 group. In compound III these dimers are arranged along to c axis while in compound V they are along 335 the b axis. Also, the molecular packing in V present two ‫ܥ‬ ଵ ଵ ሺ7ሻ and one ‫ܥ‬ ଵ ଵ ሺ9ሻ chain along the c axis. Comprehensive 348 review on current developments of quinoline-based anticancer agents Quinoline biodegradation by 351 filamentous fungus Cunninghamella elegans and adaptive modifications of the fungal 352 membrane composition Benzothiazepine Derivatives Bearing Quinoline Moiety A comprehensive study on crystal structure of a novel sulfonamide-359 dihydroquinolinone through experimental and theoretical approaches Analysis 362 of two novel 1-4 quinolinone structures with bromine and nitrobenzyl ligands Synthesis, Characterization 365 and Conformational Analysis of Two Novel 4(1H)⁰Quinolinones Different reactivity to glutathione but similar tumor cell 369 toxicity of chalcones and their quinolinone analogues Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal 374 structure, and molecular modeling studies Machine 377 learning prediction of the potential pesticide applicability of three dihydroquinoline 378 derivatives: Syntheses, crystal structures and physical properties Design, synthesis and 381 evaluation of novel 2,2-dimethyl-2,3-dihydroquinolin-4(1H)-one based chalcones as 382 cytotoxic agents Synthesis, characterization and anticancer activity of novel ferrocene 385 containing quinolinones: 1-Allyl-2-ferrocenyl-2,3-dihydroquinolin-4(1H)-ones and 1-386 allyl-2-ferrocenylquinolin-4(1H)-ones Synthesis of 3-Methylidene-1-tosyl-390 2,3-dihydroquinolin-4(1 H )-ones as Potent Cytotoxic Agents Toluenesulfonic acid mediated one-pot cascade synthesis and cytotoxicity evaluation 394 of polyfluorinated 2-aryl-2,3-dihydroquinolin-4-ones and their derivatives Synthesis and biological evaluation 398 of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives as potential 399 MERS-CoV inhibitors Qsar Modeling: a New Open Source Computational Package To Generate and Validate Qsar Models OLEX2: 408 A complete structure solution, refinement and analysis program A short history of SHELX Crystal structure refinement with SHELXL PARST 95 -an update to PARST : a system of Fortran routines for 415 calculating molecular structure parameters from the results of crystal structure 416 analyses Single-crystal structure validation with the program PLATON Characterization 420 and Evaluation of in vitro Antitumor Activities of Novel Chalcone Hybrid Compounds Selective Trypanosoma cruzi trans-Sialidase Inhibitors from Sulfonamide Chalcones 425 and Their Derivatives Promoted Cascade Reaction to Synthesize 3-Benzyl-2-phenylquinolin-4(1 H)-ones Tandem chalcone-sulfonamide hybridization, 432 cyclization and further Claisen-Schmidt condensation: Tuning molecular diversity 433 through reaction time and order and catalyst Graph-set analysis of hydrogen-bond patterns: some 436 mathematical concepts