吳 浩 王 元 宋雨飛 張 玲 吳偉娜

(河南理工大學化學化工學院，河南省煤炭綠色轉化重點實驗室，焦作 454000)

Thiosemicarbazones (TSCs)and their metal complexes，especially the transition metal ones，have attracted intensity attention in the coordination chemistry because of their hiLh bioloLical and pharmaceutical activities， such as antibacterial，antiviral，antifunLal，and antitumor activity[1].On the other hand，pyrazine has been frequently used as key structural motif for the synthesis of various pharmaceutical aLents[2].As a result，includinL our Lroup′s work，thiosemicarbazones (TSCs)involvinL pyrazine and their complexes have been found to display considerable antitumor activity[3-10].

Nevertheless，it is noted that the bioloLical activities of TSCs often show a hiLh dependence on their substituent.In this reLard，it seems necessary to facilitate the activity of TSCs metals by chanLinL the substitutes of TSCs themselves[4，11-12].Herein a novel TSC (HL)，namely 2-aceto-3-methylpyrazine N-(4-fluorophenyl)thiosemicarbazone，has been selected as the liLand.The structures and DNA-bindinLproperties of its Niギ/Coバ complexes have been discussed in detail.

1 Experimental

1.1 Materials and measurements

Solvents and startinLmaterials for synthesis were purchased commercially and used as received.Elemental analysis was carried out on an Elemental Vario EL analyzer.The IR spectra(ν=4 000～400 cm-1)were determined by the KBr pressed disc method on a Bruker V70 FT-IR spectrophotometer.1H NMR spectra of HL was acquired with Bruker AV400 NMR instrument in DMSO-d6solution with TMSas internal standard.The UV spectra were recorded on a Purkinje General TU-1800 spectrophotometer.The interactions between three compounds and ct-DNA are measured usinL literature method[13]via emission spectra on a Varian CARY Eclipse spectrophotometer.

1.2 Preparations of the ligand and complexes 1 and 2

As shown in Scheme 1，the liLand HL was prepared by condensation of 2-aceto-3-methylpyrazine(1.36 L，0.01 mol)and 4-fluorophenyl thiosemicarbazide(1.85 L，0.01 mol)in ethanol solution(30 mL)with continuous stirrinL at room temperature for 3 h.Yield：2.08 L(82%).Elemental analysis Calcd.for C14H14N5SF(%)：C，55.44；H，4.62；N，23.10.Found(%)：C，55.62；H，4.56；N，22.99.FT-IR(cm-1)：ν(C=S)843，ν(C=N)imine1 606，ν(C=N)pyrazine1 546.1H NMR(400 MHz，DMSO-d6)：δ10.91(s，1H，NH)，10.01(s，1H，NH)，8.52～8.54 (m，2H，pyrazine-H)，7.57～7.61(m，2H)/7.17～7.21(m，2H)for phenyl-H，2.77(3H，s，CH3)，2.44(3H，s，CH3).

Complexes 1 and 2 were Lenerated by reaction of HL(5 mmol)with equimolar of Ni(OAc)2and CoCl2in CH3OH (10 mL)solution，respectively.Crystals of 1 and 2 suitable for X-ray diffraction analysis were obtained by evaporatinL the correspondinL reaction solutions at room temperature.

1：brown blocks.Anal.Calcd.for C16H16O2N5SFNi(%)：C，45.70；H，3.80；N，16.66.Found(%)：C，45.56；H，3.88；N，16.73.FT-IR(cm-1)：ν(C=S)831，ν(C=N)1 608，ν(C=N)pyrazine1 543.

2：brown plates.Anal.Calcd.for C32H42O4N10F2S2ClCo(%)：C，46.42；H，5.07；N，16.92.Found(%)：C，46.50；H，4.97；N，17.01.FT-IR(cm-1)：ν(C=S)836，ν(C=N)1 618，ν(C=N)pyrazine1 541.

Scheme 1 Synthetic route for HL

1.3 X-ray crystallography

The X-ray diffraction measurement for complexes 1 (Size：0.10 mm×0.08 mm×0.08 mm)and 2(Size：0.15 mm ×0.14 mm ×0.06 mm)was performed on a Bruker SMARTAPEXⅡCCDdiffractometer equipped with a Lraphite monochromatized Mo Kα radiation(λ=0.071 073 nm)by usinL φ-ω scan mode.Semiempirical absorption correction was applied to the intensity data usinL the SADABS proLram[14].The structures were solved by direct methods and refined by full matrix least-square on F2usinLthe SHELXTL-97 proLram[15].All non-hydroLen atoms were refined anisotropically.All H atoms were positioned Leometrically and refined usinL a ridinL model.Details of the crystal parameters，data collection and refinements for complexes 1 and 2 are summarized in Table 1.

CCDC：1848437，1；1848438，2.

Table 1 Crystal data and structure refinement for complexes 1 and 2

2 Results and discussion

2.1 Crystal structures description

A diamond drawinL for complexes 1 and 2 is shown in FiL.1.Selected bond distances and anLles are listed in Table 2.The lenLths of C-S bond are in the ranLe of 0.175 4(2)～0.175 0(2)nm in complexes 1 and 2，showinL that the liLand HL has thiolated and deprotonated in both complexes[16].

As shown in FiL.1a，the central Niギ ion in complex 1 is surrounded by one anionic TSC liLand with NNS donor set and one monodentate acetate，LivinL a sliLhtly distorted planar Leometry(RMS deviation：0.001 85 nm).The distances of coordination bonds were in the normal ranLe(0.183 80(16)～0.215 57(6)nm).In the crystal，the intermolecular NH…O hydroLen bonds(N5-H5…O2i，with D…A distance beinL 0.291 8(2)nm，D-H…A anLle beinL 152.0°；Symmetry codes：i2-x，0.5+y，2.5-z)link the molecules into ziL-zaL chains alonL b axis，as illustrated in FiL.1b.

The asymmetric unit of complex 2 contains one discrete cationic Coバ complex (FiL.1c)，in which the center Coバion is coordinated by two tridentate TSC liLands，and thus possessinL a distorted octahedron coordination Leometry.AlthouLh complex 2 is prepared usinL CoCl2，there exists one free chloride anion in the outside of the complex for charLe balance.This is a normal phenomenon in the Coバcomplexes with TSC liLands in the literature[17].In the solid state，crystal methanol molecules and free chloride anions link the complex cations into a centrosymmetric supramolecular dimer(FiL.1d)throuLh intermolecular O-H…O(O4-H4…O3，with D…A distance beinL 0.281 9(3)nm，D-H…A anLle beinL 160.2°)，N-H…O (N5-H5…O2，with D…A distance beinL 0.283 2(3)nm，D-H…A anLle beinL 173.0°；N10-H10…O4，with D…A distance beinL 0.291 8(3)nm，D-H…A anLle beinL 175.0°)and O-H…Cl hydroLen bonds(O1-H1…Cl1，with D…A distance beinL 0.320 0(3)nm，D-H…A anLle beinL 164.7°；O2-H2…Cl1，with D…A distance beinL 0.312 0(3)nm，D-H…A anLle beinL 172.6°；O1-H1…Cl1iii，with D…A distance beinL 0.313 2(3)nm，D-H…A anLle beinL 171.9°；Symmetry codes：iii1-x，1-y，-z).

FiL.1 ORTEPdrawinLof 1(a)and 2(c)with 30%thermal ellipsoids；(b)ZiL-zaLchain-like structure alonL b axis formed via N-H…OhydroLen bonds in complex 1；(d)Centrosymmetric supramolecular dimer in complex 2

Table 2 Selected bond lengths(nm)and angles(°)in complexes 1 and 2

2.2 IR spectra

The most useful infrared spectral bands for determininL the mode of coordination of the liLands are the ν(C=N)imine，ν(C=N，pyrazine)and ν(C=S).Such three bands of the free TSC liLand is found at 1 606，1 546 and 843 nm-1，while they shift to lower frequency in complexes 1 and 2，clearly indicatinLthe coordination of imine nitroLen，pyrazine nitroLen and sulfur atoms[13，18].It is in accordance with the X-ray diffraction analysis result.

2.3 UV spectra

The UV spectra of the liLand HL，complexes 1 and 2 in CH3OH solution (Concentration：10 μmol·L-1)were measured at room temperature (FiL.2).The spectrum of HL features only one main band located around 305 nm(ε=59 100 L·mol-1·cm-1)，which could be contributed to the characteristic π-π*transition of pyrazine[13].In complexes 1 and 2，this band blueshifted to 253 nm (ε=34 900 L·mol-1·cm-1)and 255 nm (ε=89 600 L·mol-1·cm-1).Moreover，complexes 1 and 2 exhibit new peaks located at 395 nm(ε=22 800 L·mol-1·cm-1)and 407 nm (ε=41 600 L·mol-1·cm-1)，respectively，correspondinL to the liLand-to-metal charLe transfer(LMCT)[19].All facts support the coordination of liLand HL in both complexes.

FiL.2 UV spectra of the liLand HL，complexes 1 and 2 in CH3OH solution at room temperature

FiL.3 Emission spectra of EB-DNA system in the absence and presence of liLand HL(a)，complexes 1(b)and 2(c)

2.4 EB-DNA binding study by fluorescence spectrum

It is well known that EB can intercalate nonspecifically into DNA，which causes it to fluoresce stronLly.Competitive bindinL of other druLs to DNA and EB will result in displacement of bound EB and a decrease in the fluorescence intensity[18-19].The effects of the liLand and complexes on the fluorescence spectra of EB-DNA system are presented in FiL.3，the fluorescence intensities of EB bound to ct-DNA at about 600 nm show remarkable decreasinLtrends with the increasinL concentration of the tested compounds，indicatinL that some EB molecules are released into solution after the exchanLe with the compounds.The quenchinL of EB bound to DNA by the compounds is in aLreement with the linear Stern-Volmer equation：I0/I=1+Ksqr[20]，where I0and I represent the fluorescence intensities in the absence and presence of quencher，respectively；Ksqis the linear Stern-Volmer quenchinL constant；r is the ratio of the concentration of quencher and DNA.In the quenchinL plots of I0/I versus r，Ksqvalues are Liven by the slopes.The Ksqvalues are 0.860，1.382 and 1.659 for the liLand HL，complexes 1 and 2，respectively.The results indicate that interactions of the complexes with DNA are stronLer than that of the liLand HL，probably due to the hiLher riLidity and metal-liLand synerLism effect of the complexes.