untitled ISSN 215 Synthes activity Mouayed 1 Department of 2 School of Chem * Corresponding Tel.: +964.40.78 ARTICLE IN DOI: 10.5155/e Received: 01 No Received in rev Accepted: 18 No Published onlin Printed: 31 Mar KEYWORDS DNA cleavage Gel electrophor Thiosemicarbaz Electronic trans Fluorescence em X‐ray single cry 1. Introduct Thiosem their chem carbazones antiviral, ant 9]. The biolo for their alde ONS donor structure fo carbazones l are straight structural d biological ac tumor activ conformation are that po compounds because of biotechnolog ment of new suitable chel artificial nuc 53‐2249 (Print) sis, structu of new th Abdulaali H f Chemistry, College mical Science, Unive g author at: Depart 800196370. Fax: +9 FORMATION eurjchem.7.1.1‐7.13 ovember 2015 vised form: 16 Nov ovember 2015 ne: 31 March 2016 rch 2016 S resis zone sition mission ystal structure tion micarbazones ha motherapeutic are importan timalarial, anti ogical activity of ehyde or keton ligands and or many tran igands attract c tforward to diversity [15,1 ctivities of thios vity are a fun nal structures, ossess the tran to cleave DN such compou gy, structural st w drugs [21‐23 lating agents fo cleases because / ISSN 2153‐225 Europ ural and s hiosemica Hussein 1,2,* a e of Science, Univer ersiti Sains Malaysi tment of Chemistry, 964.40.7800196370 354 ember 2015 ave received m applications nt compounds fungal and ant f thiosemicarba e moiety, which provide a su sition metals considerable at synthesize an 16]. Recent st semicarbazones nction of the the most acti ns isomer [17 NA has receiv unds can be tudies of nucle 3]. Thiosecarba or metal ions w e of their variou European Jour Europ 57 (Online)  20 http://dx.doi.or pean Jo Journal web spectral c arbazone and Teoh Sia rsity of Basrah, Bas ia, Minden, Pulau P y, College of Science 0. E‐mail address: m ABSTRACT Two new com and (E)‐N‐eth been synthesi UV‐Vis, 1H an spectroscopy. single crystal remain as a conformation 322 has been a significant n by substituen Cite this: Eur. more attention d [1‐4]. Thio s because of titumor activiti azones are a fun h acts as a tride itable complex [10‐14]. Thio ttention becaus nd have scop tudies showed s especially the ir geometrical ve thiosecarba ‐20]. The abil ved more atte used as agen eic acids, or dev azones are one which can be us us structural fea nal of Chemistry pean Journal of C 016 Atlanta Pub rg/10.5155/eurj ournal bpage: www. characteri derivativ ang Guan 2 rah, 61001, Iraq Pinang, 11800, Mala e, University of Basr mouayed_505emar@ mpounds, (E)‐2 hyl‐2‐((2‐hydrox ized. The prepar nd 13C NMR sp . The molecular l diffraction ana a thione form nal and symmetr investigated us nuclease activity t moieties of the . J. Chem. 2016, due to osemi‐ their es [5‐ nction entate xation osemi‐ e they e for d the e anti‐ l and azones ity of ention nts in velop‐ e of a ing as atures and coo ava Her X‐ra pBR com 2. E 2.1. Ald pur Scie reco usin on scen pho Bru shif y 7 (1) (2016) 1‐ Chemistry lishing House LL chem.7.1.1‐7.13 of Che .eurjchem.co ization, an ves aysia rah, Basrah, 61001, @yahoo.com (M. H 2‐(3‐ethoxy‐2‐hy xynaphthalen‐1‐ red compounds pectroscopic tec structures of the alysis. The cryst in the solid s ical structures. T ing agarose gel y which was attr e compound. 7(1), 1‐7 d their ability ordinated with t To our best kn ailable regardin re, we presen ay single cryst R 322 plasmi mpounds. Experimental . Materials and All the reagent rich were of rification. Melt entific SMP1 m orded on a Per ng the KBr disc a Perkin Elm nce spectra w otometer. 1H NM uker 500 MHz u ft values are rep ‐7 LC ‐ All rights re 354 emistry m nd in vitr , Iraq. Hussein). ydroxybenzylide yl)methylene)hy have been char chniques as we e compounds ha tal structures re state and are The nuclease act electrophoresis ributed to the lip to change th these ligands [2 nowledge, there ng the DNA clea t the synthes al structure an d DNA for t d methods ts and solvents reagent grade ting point wa melting point ap rkin Elmer Syst c method. UV‐V er Lambda‐35 were recorded MR and 13C NM using DMSO‐d6 ported in ppm f served ‐ Printed y o nucleas ne)hydrazineca ydrazinecarboth acterized by CH ell as the fluore ave also been det evealed that the different in th tivity of compou assay. The com pophilic propert heir redox po 24,25]. e is still very litt avage by thiose is, spectral ch nd nuclease act two new thio s were purchase e and used w as measured b pparatus. FT‐IR tem 2000 spec Visible spectra spectrophoto on a Jasco FP R spectra were 6 as the solvent from TMS. d in the USA se rbothioamide ( hioamide (2) hav HN analysis, FT‐I escence emissio termined by X‐ra e compounds a heir geometrica nds to cleave pB mpound 2 reveale ties that provide otential during tle information emicarbazones. haracterization, tivity to cleave semicarbazone ed from Sigma‐ without further by the Stuart R spectra were ctrophotometer were recorded meter. Fluore‐ P‐750 spectro‐ e recorded on a t. The chemical 1) ve R, on ay re al, BR ed ed g n . , e e ‐ r t e r d ‐ ‐ a l 2 Hussein and Guan / European Journal of Chemistry 7 (1) (2016) 1‐7 Scheme 1 Scheme 2 Elemental analysis was conducted using a Perkin Elmer 2400 Series‐11 CHN analyzer. X‐ray crystallographic data were recorded on a Bruker SMART APEXII CCD area‐detector diffractometer using graphite monochromated MoKα radiation (λ = 0.71073 Å) at 100 K. The data were collected and reduced using APEX2 and SAINT programs. The structure of all compounds was solved using the SHELXS‐97 program package, and refined using the SHELXL‐97 program package. All non‐hydrogen atoms were anisotropically refined. The molecular graphics were created using SHELXTL‐97 [26]. 2.2. Nuclease activity assay The nuclease activity of compound 1 and 2 to cleave pBR322 plasmid DNA was studied using agarose gel electrophoresis technique in Tris/EDTA buffer solution. The samples were prepared by mixing appropriate quantities from DNA, compound and H2O2. Then incubated at 37 °C for 2 h, treated with loading dye, and electrophoresed for 1 h at 50 V on 1% agarose gel consisting of 12 lanes: lane 1, pBR322 DNA (0.025 µM); lane 2, DNA (0.025 µM) + compound (6 µM); lane 3, DNA (0.025 µM) + H2O2 (4.5 µM); lane 4, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (1 µM); lane 5, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (2 µM); lane 6, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (3 µM); lane 7, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (3.5 µM); lane 8, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (4 µM); lane 9, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (4.5 µM); lane 10, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (5 µM) and lane 11, DNA (0.025 µM) + H2O2 (4.5 µM) + compound (6 µM). The gel was then stained with ethidium bromide before being photographed under UV light. The results were controlled using 1 kbp ladder DNA (lane, L). 2.3. General procedure for the synthesis of compound 1 and 2 A solution of the corresponding aldehyde in ethanol (20 mL) was added to an ethanolic solution (20 mL) of thiosemicarbazide (5.48 mmol) or 4‐ethyl‐3‐thiosemicar‐ bazide (4.19 mmol). The resulting yellow solution was refluxed with stirring for 2 h (Scheme 1). The product was isolated by filtration, washed with ethanol and dried. Plate colorless and needle yellow were obtained by slow evaporation of DMF for compound 1 and 2, respectively. (E)‐2‐(3‐Ethoxy‐2‐hydroxybenzylidene)hydrazinecarbo thioamide (1): Yield: 79%. M.p.: 181‐183 °C. FT‐IR (KBr, ν, cm‐ 1): 3317 (OH), 1609 (C=N), 1550 (CaroO), 1275 (C=S). 1H NMR (500 MHz, DMSO‐d6, δ, ppm): 1.37 (t, 3H, CH3), 4.04 (q, 2H, CH2), 6.57 (t, 1H, Ar‐H), 6.91 (d, 1H, Ar‐H), 7.50 (d, 1H, Ar‐H), 7.87 (s, 1H, NH2), 8.03 (s, 1H, NH2), 8.41 (s, 1H, CH=N), 9.13 (br, 1H, OH), 11.40 (s, 1H, N‐NH). 13C NMR (125 MHz, DMSO‐d6, δ, ppm): 14.50 (CH3), 64.15 (CH2), 114.06‐146.17 (C‐Aromatic), 146.95 (C=N), 177.51 (C=S), Anal. calcd. for C10H13N3O2S: C, 50.19; H, 5.48; N, 17.56. Found: C, 50.17; H, 5.48; N, 17.52%. UV‐Vis (DMSO, λmax, nm): 295, 312. (E)‐N‐Ethyl‐2‐((2‐hydroxynaphthalen‐1‐yl) methylene) hydrazinecarbothioamide (2): Yield: 90%. M.p.: 213‐215 °C. Anal. calcd. for C14H15N3OS: C, 61.51; H, 5.53; N, 15.37. Found: C, 61.43; H, 5.46; N, 15.35%. FT‐IR (KBr, ν, cm‐1): 3405 (OH), 3149 (N‐NH), 1600 (C=N), 1537 (CaroO), 1264 (C=S). 1H NMR (500 MHz, DMSO‐d6, δ, ppm): 1.18 (t, 3H, CH3), 3.62 (dd, 2H, CH2), 7.22 (d, 1H, Ar‐H), 7.39 (t, 1H, Ar‐H), 7.57 (t, 1H, Ar‐H), 7.85 (dd, 2H, Ar‐H), 8.38 (bt, 1H, CS‐NH), 8.46 (d, 1H, Ar‐H), 9.06 (s, 1H, CH=N). 13C NMR (125 MHz, DMSO‐d6, δ, ppm): 14.49 (CH3), 30.62 (CH2), 109.77‐142.61 (C‐aromatic), 156.30 (C=N), 177.42 (C=S); UV‐Vis (DMSO, λmax, nm): 320, 330, 370. 3. Results and discussion 3.1. Synthesis The (E)‐2‐(3‐ethoxy‐2‐hydroxybenzylidene)hydrazine carbothioamide (1) and (E)‐N‐ethyl‐2‐((2‐hydroxynaphthalen‐ 1‐yl)methylene)hydrazinecarbothioamide (2) were prepared by the condensation reaction of 3‐ethoxy‐2‐hydroxybenz‐ aldehyde and thiosemicarbazide or 2‐hydroxy‐1‐naphthalde‐ hyde and 4‐ethyl‐3‐thiosemicarbazide (Scheme 1). The com‐ pounds may exist in two tautomeric forms, either thione or thiol form (Scheme 2). The compounds are air stable and soluble in DMF, DMSO, and rare soluble in H2O. 3.2. FT‐IR analysis The bands appeared at 3405 and 3149 cm‐1 are attributed to the ν(OH) and ν(N‐NH) for compound 2, respectively. The imino group (C=N) for compound 2 gave a band at 1600‐1609 cm‐1. The strong band observed at 1550 and 1537 cm‐1 is attributed to ν(Caro O) for compound 1 and 2, respectively. The thione grou stretching ba 3.3. 1H NMR The 1H N Figure 1 and at δ 1.37 ppm δ 4.04 ppm between the at δ 6.57 ppm and 7.50 pp 8.03 ppm are broad signa signals at δ 8 N‐NH proton Figur Figur In comp attributed to attributed to CH3 and NH protons prod signals at δ 7 the interacti signal at δ 7 at δ 8.46 ppm ppm is attri interaction o state of the p signal. The C ppm. p (C=S) for c and at 1275 and analysis NMR spectra o d 2, respectively m is attributed t m is attributed e aromatic proto m, and doublet m, respectively e attributed to N l at δ 9.13 pp 8.41 and 11.40 p ns. re 1. 1H NMR spec re 2. 1H NMR spec pound 2, the o CH3 protons, o CH2 protons r H protons. The duces doublet s 7.39 and 7.57 p ion of C3‐H and .85 ppm, wher m. The broad tr ibuted to CS‐N of 14N (I = 1) cau protons which l CH=N proton ap Hussein and ompound 1 a d 1264 cm‐1, res f compound 1 y. In compound to CH3 protons, to CH2 proto ons produces t t signals for C4‐ y. The singlet s NH2 protons. Th pm, whereas t ppm are attribu trum of compound trum of compound triplet signal the quintet sig resulting from interaction be signal at δ 7.22 ppm for C6‐H an d C4‐H results a reas the C8‐H sh riplet signal tha NH proton, the uses to lower th leads to broade ppeared as a sin d Guan / Europea nd 2 gave a spectively. and 2 are sho d 1, the triplet , the quartet sig ons. The intera riplet signal for H and C6‐H at δ signals at δ 7.8 he OH proton s the observed s uted to the CH= d 1 in DMSO‐d6. d 2 in DMSO‐d6. at δ 1.18 pp gnal at δ 3.62 p the interaction etween the aro ppm for C5‐H, t nd C7‐H, respect a doublet of do how a doublet at emerged at δ nuclear quadr he lifetime of ex en the resulting nglet signal at δ an Journal of Che sharp wn in signal gnal at action r C5‐H δ 6.91 7 and how a singlet N and pm is ppm is n with omatic triplet tively, oublet signal δ 8.38 rupole xcited g NMR δ 9.06 3.4. CH3 of C δ 6 The from 109 attr are 3.5. sho ratu and aro thio abs π → tran 3.6. sho tem π* → qua that sho 1 s form rigi clos lead 3.7. pou (Å), 3 an Figu clos whi app thre mistry 7 (1) (201 . 13C NMR analy Both the comp 3 at δ 14.50 ppm CH2 to downfiel 4.15 and 30.62 e aromatic carb m δ 114.06 to 1 9.77 to 142.61 ributed to the c appeared at δ 1 . UV‐Visible an The electronic own in Figure 3 ure. The compo d 312 nm whic matic ring and olate function, orption bands → π* transition, nsition. Figure 3. Ele . Fluorescence The fluorescen own in Figure mperature. The → π transition r antum efficienc t for the π* → ow a fluorescenc show second e mation of exci dity and steric se enough to l ds to generate a . X‐ray crystall The crystal d unds 1 and 2 ar , bond angles (° nd 4, respectiv ure 5 and 6, res The compoun se to the molec ich was isolate proximation, th ee significant d 16) 1‐7 ysis pounds 1 and m. The oxygen a ld more than n 2 ppm for com bons of compo 146.17 ppm, wh 1 ppm. The s carbon of C=S a 146.95 ppm for alysis c transition sp 3, were measur ound 1 show t h are attribute d n → π* trans respectively. T at 320 and 33 , and at 370 nm ctronic transitions analysis nce emission s e 4, were me fluorescence e rather than the y is greater an n transition [2 ce emission ban emission band imer molecule c features suc limit that allow an excimer mol lography diffra data and refin re summarized °) and torsion a vely. The molec spectively. d 1 is a secon cule B of the pr ed from an eth he molecular st ifferences are n 2 show the ca atom shifted th nitrogen atom w mpound 1 and 2 und 1 appeare hereas for comp signal at δ 1 and, the carbon r compound 1. pectra of comp red in DMSO a two absorption ed to the π → π sition of the az The compound 0 nm which ar m which attribu s of the compounds pectra of comp easured in DM emission is att π* → n transiti nd the lifetime 27]. The compo nds at 378 nm. at 520 nm m e, which is ari ceed to bring ws to energy t ecule [28]. action analysis ement parame d in Table 1. Th angles (°) are gi cular structures nd monoclinic reviously report hanol solution tructure found noted. 3 arbon signal of e carbon signal which shown at 2, respectively. ed in the range pound 2 from δ 77.51 ppm is signals of C=N pound 1 and 2 at room tempe‐ n bands at 295 π* transition of zomethine and 2 show three re attributed to uted to n → π* s 1 and 2. pound 1 and 2 MSO at room tributed to the ion because the is shorter than ounds 1 and 2 The compound may be due to ises when the the molecules transfer which s eters for com‐ he bond lengths iven in Table 2, s are shown in (P21/c) and is ted (P21) form, [29]. To a first is similar, but f l t . e δ s N 2 ‐ 5 f d e o * 2 m e e n 2 d o e s h ‐ s , n s , t t 4 Hussein and Guan / European Journal of Chemistry 7 (1) (2016) 1‐7 Table 1. Crystal data and refinement parameters for compounds 1 and 2. Parameter Compound 1 Compound 2 Chemical formula C10H13N3O2S C14H15N3OS Formula weight 239.30 273.36 Crystal system Monoclinic Monoclinic Crystal description Plate colorless Needle yellow Space group P21/c P21 a (Å) 12.8547(5) 9.2934(14) b (Å) 5.9945(2) 5.0115(8) c (Å) 16.0739(7) 14.736(2) α (°) 90 90 β (°) 100.494(2) 103.620(3) γ (°) 90 90 Volume (Å3) 1217.90(8) 667.01(17) Z 4 2 Dcalc (g/cm3) 1.305 1.361 Crystal size (mm) 0.07 × 0.11 × 0.49 0.03 × 0.09 × 0.50 Temperature (K) 100 100 Total data 16551 7884 Unique data 3589 3684 Rint 0.043 0.038 Observed data [I>2σ(I)] 2785 3196 R1 0.0478 0.0401 wR2 0.1025 0.0971 S 1.04 1.05 Table 2. Bond lengths for compound 1 and 2. Atom Atom Length, Å Atom Atom Length, Å Compound 1 S1 C8 1.7017(16) C1 C6 1.391(2) O1 C1 1.3658(17) C1 C2 1.409(2) O2 C2 1.3675(18) C2 C3 1.386(2) O2 C9 1.4450(18) C3 C4 1.405(2) N1 C7 1.2845(19) C4 C5 1.379(2) N1 N2 1.3795(17) C5 C6 1.408(2) N2 C8 1.3470(19) C6 C7 1.460(2) N3 C8 1.327(2) C9 C10 1.507(2) Compound 2 S1 C12 1.6856(19) C3 C4 1.419(3) O1 C1 1.355(2) C4 C5 1.423(3) N1 C11 1.296(2) C4 C9 1.432(2) N1 N2 1.379(2) C5 C6 1.372(3) N2 C12 1.357(2) C6 C7 1.412(3) N3 C12 1.339(2) C7 C8 1.371(3) N3 C13 1.464(3) C8 C9 1.420(2) C1 C10 1.403(2) C9 C10 1.437(3) C1 C2 1.411(3) C10 C11 1.453(3) C2 C3 1.368(3) C13 C14 1.520(2) Table 3. Bond angles for compound 1 and 2. Atom Atom Atom Angle, ° Atom Atom Atom Angle, ° Compound 1 C2 O2 C9 117.59(12) C5 C4 C3 120.98(14) C7 N1 N2 115.06(13) C4 C5 C6 120.29(14) C8 N2 N1 120.20(13) C1 C6 C5 118.82(13) O1 C1 C6 119.52(13) C1 C6 C7 119.27(13) O1 C1 C2 119.69(13) C5 C6 C7 121.89(13) C6 C1 C2 120.78(13) N1 C7 C6 120.92(13) O2 C2 C3 126.39(14) N3 C8 N2 117.09(14) O2 C2 C1 113.67(13) N3 C8 S1 123.86(12) C3 C2 C1 119.93(14) N2 C8 S1 119.05(11) C2 C3 C4 119.19(14) O2 C9 C10 107.23(14) Compound 2 C11 N1 N2 115.99(14) C8 C7 C6 121.40(17) C12 N2 N1 120.78(15) C7 C8 C9 121.31(17) C12 N3 C13 124.43(17) C8 C9 C4 117.53(17) O1 C1 C10 122.55(17) C8 C9 C10 123.23(16) O1 C1 C2 115.94(16) C4 C9 C10 119.23(15) C10 C1 C2 121.50(17) C1 C10 C9 118.75(16) C3 C2 C1 119.91(16) C1 C10 C11 120.58(17) C2 C3 C4 121.37(18) C9 C10 C11 120.64(15) C3 C4 C5 121.33(17) N1 C11 C10 122.02(16) C3 C4 C9 119.23(17) N3 C12 N2 116.47(16) C5 C4 C9 119.44(16) N3 C12 S1 123.33(15) C6 C5 C4 121.48(19) N2 C12 S1 120.20(13) C5 C6 C7 118.83(19) N3 C13 C14 108.89(18) The compound 1 which was isolated from the DMF solution show the syn configurations of O1 atom with respect to O2 atom (torsion angle: O1‐C1‐C2‐O2 = 0.16(19)°) and C2 atom with respect to C5 atom (torsion angle: C1‐C2‐C3‐C5 = 0.6(2)°), whereas in the reported P21 form, the corresponding atoms of molecule B show the anti configurations of O3 atom with respect to O4 (torsion angle: O3‐C11‐C12‐O4 = ‐1.1(7)°) and C12 atom with respect to C15 (torsion angle: C12‐C13‐ C14‐C15 = ‐0.8(8)°). Table 4. Torsio A B Compound 1 C7 N1 C9 O2 C9 O2 O1 C1 C6 C1 O1 C1 C6 C1 O2 C2 C1 C2 C2 C3 C3 C4 O1 C1 Compound 2 C11 N1 O1 C1 C10 C1 C1 C2 C2 C3 C2 C3 C3 C4 C9 C4 C4 C5 C5 C6 C6 C7 C7 C8 C7 C8 C3 C4 C5 C4 C3 C4 C5 C4 Figure 4. F In additi C3 atom with = ‐0.7(2)°), show the syn 1.2(8)°). Mo 100.494(2)°, and equal to the calculate are 0.0478, P21/c and P2 on angles for comp C N2 C2 C2 C2 C2 C2 C2 C3 C3 C4 C5 C6 N2 C2 C2 C3 C4 C4 C5 C5 C6 C7 C8 C9 C9 C9 C9 C9 C9 Fluorescence emiss Figure 5. Molecul on, the compou h respect to C6 whereas the n configuration reover, the val , whereas that o 90.238(3)°. A ed refinement p 0.1025 and 1.0 21, respectively Hussein and pound 1 and 2. D Angl C8 176.3 C3 ‐7.0( C1 172.1 O2 0.15( O2 ‐179 C3 179.3 C3 0.1(2 C4 178.7 C4 ‐0.3( C5 0.6(2 C6 ‐0.7( C5 ‐179 C12 ‐177 C3 ‐178 C3 0.9(3 C4 ‐0.4( C5 179.2 C9 0.0(3 C6 ‐179 C6 ‐0.7( C7 0.8(3 C8 ‐0.4( C9 ‐0.3( C4 0.4(3 C10 179.6 C8 179.3 C8 0.0(2 C10 0.1(2 C10 ‐179 sion spectra of the ar structure of com und 1 show the 6 atom (torsion corresponding (torsion angle: lue of β angle for the reporte A significant di parameters of R 04; and 0.056, y. Furthermore d Guan / Europea le, ° 36(14) (2) 11(13) (19) .14(13) 34(13) 2) 79(14) (2) 2) (2) .43(13) .57(17) .89(17) 3) (3) 26(18) 3) .95(19) (3) 3) (3) (3) 3) 66(18) 33(18) 2) 2) .24(17) compounds 1 and mpound 1. anti configurat angle: C3‐C4‐ atoms of molec : C13‐C14‐C15‐ in the P21/c fo ed P21 is close t fference arises R1, wR2 and S, w 0.119 and 0.9 , the compound an Journal of Che A C2 O1 C2 C4 C4 N2 C1 C5 N1 N1 C2 O1 C2 O1 C2 C8 C4 C8 C4 N2 C1 C9 C13 C13 N1 N1 C12 d 2. tion of C5‐C6 cule B ‐C16 = orm is to 90° s from which 92, for d 1 in P21 cen on t C9 geo rela of in 2, th tran The bon the in r are Å, r exis com syst sym firs incl C4, seco thir mistry 7 (1) (201 B C1 C1 C1 C5 C5 N1 C6 C6 N2 N2 O2 C1 C1 C1 C1 C9 C9 C9 C9 N1 C10 C10 N3 N3 N2 N2 N3 1/c form is cent ntrosymmetric [ Figure The prepared the geometry o atom. In com ometry in relat ation to C5 ato ntrahydrogen b he N1 show the ns geometry in ese geometries nding of O1‐H∙∙∙ cis geometry in relation to S1 a 1.7015(18) an respectively. Th st in thione fo mplexation to th Moreover, the tem with the mmetric as show t plane includ ludes O1, C1, C2 O2, C9 and C1 ond planes is rd planes is 17 16) 1‐7 C D C6 C C6 C C6 C C6 C C6 C C7 C C7 N C7 N C8 N C8 S C9 C C10 C C10 C C10 C C10 C C10 C C10 C C10 C C10 C C11 C C11 N C11 N C12 N C12 S C12 N C12 S C13 C trosymmetric, w [30]. e 6.Molecular struc compounds sh of N1 atom in r mpound 1, the tion to C1 ato m. These geom bonding of O1‐H e cis geometry i n relation to th s allow the N1. Both the co n relation to N3 atom. The bond nd 1.347(2) Å a hese distances c orm in sold sta hiol form [31]. e compound 1 presence of wn in Figure 7 des N1‐N3, C8 2 and C5‐C7 an 0. The dihedral 176.36(14)°, a 72.11(13)°. By D Angle, ° C5 ‐0.1(2) C7 ‐1.0(2) C7 178.34( C1 0.5(2) C7 ‐177.96 C6 177.22( N1 ‐174.45 N1 4.0(2) N3 ‐3.3(2) S1 176.26( C10 ‐172.87 C9 178.91( C9 ‐0.9(3) C11 ‐2.6(3) C11 177.62( C1 ‐178.85 C1 0.4(2) C11 2.7(3) C11 ‐178.10 C10 ‐179.77 N1 ‐0.2(3) N1 178.28( N2 ‐179.84 S1 0.1(3) N3 ‐3.3(3) S1 176.81( C14 ‐176.24 whereas the P2 cture of compound ow different st relation to C1 a e N1 atom sho om and the ci metries prevent H∙∙∙N1. Whereas in relation to C he correspondin formation of ompounds the N 3 atom and the d distances of and, 1.6854(19 confirmed that t ate, which are in monoclinic inversion cen 7, and show thr 8 and S1, the nd the third pla l angles betwee and between th contrast, the c 5 ° 13) (14) 13) (14) 11) (14) 17) 17) (18) (16) (16) 17) (17) 14) (19) 21 form is non‐ d 2. tructures based atom and C5 or ows the trans is geometry in t the formation s, in compound 1 atom and the ng of C9 atom. intrahydrogen N1 atom shows trans geometry S1‐C and C‐N2 ) and 1.357(3) the compounds changes upon c P21/c crystal nter is centro‐ ree planes. The second plane ne includes C3, en the first and he second and compound 2 in ‐ d r s n n d e . n s y 2 ) s n l ‐ e e , d d n 6 monoclinic P center is non two planes. C11, and the C14. The dih (17)°. Fi Fi The cry centrosymm molecular h (symmetry c ‐y, ‐z). These compound 1 the crystal s symmetrical hydrogen bo code: 1‐x, ‐1 ‐1/2+y, 2‐z) molecules to which are compound. (torsion angl H1∙∙∙N1 hydr atom in resp 0.1(3)°) is s 10). 3.8. DNA clea The ag compounds the compoun is related to At concentra compound s the open circ compound 2 the DNA stra P21 crystal syst n‐centrosymme The first plan e second plane hedral angle b igure 7. Crystal str igure 8. Crystal str stal structure metrically relat hydrogen bon code: ‐x, ‐y, ‐z), a e hydrogen bon 1 molecule in cr structure of co ly related dim onds N2–H1∙∙∙S /2+y, 1‐z), and . These hydrog o be stacked al stabilize the Moreover, the le C1–C10–C11 rogen bond, an pect to S1 atom stabilized by N avage activity garose gel e 1 and 2 are sho nd 1 show the n the closed circ ation 4.5 µM ( how the slow cular relaxed fo 2 show higher c ands to produce Hu tem with the a etric as shown i e includes the e includes N1‐N between the tw ructure planes of c ructure planes of c of compound ed dimmers nds N2–H1∙∙∙O and N3–H∙∙∙S1 ( ds are stabilizin rystal lattice (Fi mpound 2 mo mmers through S1 and C11–H d C2–H2A∙∙∙O1 ( gen bonds allo ong the b‐axis packing crysta e orientation o –N1 = ‐ 0.2(3)° nd the syn conf m (torsion angl N3–H1∙∙∙N1 hyd lectrophoresis own in Figure 1 naturally fast m cular supercoile lane 9) and 5. migration form orm (OC, form I cleavage activit e the OC form a ussein and Guan absence of inve n Figure 8, and aromatic ring N3, O1, S1 and wo planes is ‐1 ompound 1. ompound 2. d 1 molecules through the O1 and O1–H (symmetry cod ng the packing igure 9). By con lecules form ce h the intermole H11A∙∙∙S1 (sym (symmetry cod ow the compou via π‐π intera al structure o of the phenyl ) is stabilized b formation of th e C13–N3–C12 drogen bond (F patterns of 11. From lane 1 migration form w ed form (SC, fo 0 µM (lane 10 m which is relat I) [32]. Wherea ty, it can nick o t concentration / European Jour ersion d show gs and d C12‐ 179.77 form inter‐ H1∙∙∙S1 e: 1‐x, of the ntrast, entro‐ ecular metry e: 1‐x, und 2 ctions of the rings by O1– he C13 2–S1 = Figure f the 1 to 8, which orm I). 0), the ted to as, the one of n 1 µM (lan are incr toge that turn com com the the con µM pro Figu Hyd Figu Hyd of f take alon inve DM the com dep pre anio anio bac stra rnal of Chemistry ne 4). The pres increase the lip rease the affin ether with the t may be lead to n increases th mpounds show mpound 1, the s concentration size of SC ncentration of th of both comp oduct which may ure 9. Crystal pac rogen bonds are sh ure 10. Crystal pa rogen bonds are sh The DNA cleav fixed amount (4 e place in prese ne (lane 3). estigated in the SO. If the cleav DMSO leads mpounds. These pends on the co sence of H2O2. on form (Schem on involves a ckbone of DNA, and. y 7 (1) (2016) 1‐7 ence of termina pophilic proper nity with the h geometrical an o an intimate a e action of com different actio size of SC fragm of the compou fragments de he compound. F pounds (lane 1 y refers to dena cking structure of hown as dashed lin acking structure of hown as dashed lin vage study was 4.5 µM) of H2O2 ence of the com Furthermore e presence of th vage action dep to inhibit th e observations ncentration of t Our suggestion me 2) in presen a nucleophilic , which subseq 7 al N(4)‐ethyl an rties of compou hydrophobic m nd conformatio ssociation with mpound to cle on regarding th ments increases und, whereas fo ecreases with Furthermore, th 11) to DNA le aturation of DN compound 1, vie nes. f compound 2, vie nes. s investigated i 2. The cleavage mpound alone (l , the DNA he hydroxyl rad pends on the hy he nuclease a confirm that c the compounds n that the comp ce of H2O2, and c attack at t uent leads to c nd groups und 2 which are edium of DNA onal structures h DNA, which in eave DNA. The he SC form. In s with increase or compound 2 increase the he addition of 6 eads to a rigid NA. ewed along c axis. ewed along b axis. n the presence action can not lane 2) or H2O2 cleavage was dical scavenger ydroxyl radical, activity of the cleavage action s 1 and 2 but in pounds exist in the compound the phosphate cleave the DNA s e A s n e n e 2 e 6 d . . e t 2 s r , e n n n d e A Figure 11. A compounds 1 a 4. Conclusio Different the characte tives. The X‐r possess diffe The nucleas circular plas electrophore nuclease acti Supplement CCDC 95 for compou obtained fr data_request References [1]. Leigh, M Chem. 20 [2]. Hussein S. A. Poly [3]. Ali, A. Q A. Polyh [4]. Ngan, N. [5]. Hussein Majid, A 2015, 19 [6]. 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