International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August ISSN

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1 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August Crystal and molecular structure of 2-(4- methoxybenzyl)-6-phenyl-5- thiocyanatoimidazo[2,1-b][1,3,4]thiadiazole S. Vijaya, a Sujeet Kumar, b Dr.J.Tonannavar,c Dr.Vasu, d Dr. Arjunagowda.K.V, e Dr.Karki, f Department of Physics, Government First Grade College, Vijayanagar, Bangalore , India, K.L.E College Bangalore, India, Dept of Physics, Karnatak University, Dharwad , Vivekananda Degree College, Bangalore , India, Department of Physics, Government College for Women, Mandya , India, Karki K.L.E College, Bangalore Correspondence viji_shanbhag@yahoo.co.in Abstract: Cancer is the second leading cause of death in the world. Despite advances in the diagnosis and treatment, overall survival of patients still remains poor. Hence, there is an urgent need for development of new anticancer agents. Considering promising biological activity of 1,3,4-thiadiazole derivatives, in the present study, synthesis and cytotoxicity assessment of new derivatives of this ring was done. All synthesized compounds were characterized by NMR, IR and spectroscopic method. Structure was determined by single crystal XRD. Cancer is a disease in which cells can be aggressive, invasive and/or metastatic. These are three malignant properties of cancer cells that differentiate them from benign tumors which are self-limited in their growth and do not invade or metastasize (1-4). Cancer is the second leading cause of death in the world. Despite advances in the diagnosis and treatment, overall survival of patients still remains poor. Until recently, surgery, chemotherapy, radiotherapy and endocrine therapyhave been the standard treatment options available for cancer patients. This has improved survival in several types of solid tumors; however, drug toxicity and emergence of drug resistance have been the major causes of failure in treatment. Hence, there is an urgent need for discovery of new anticancer agents to overcome the disadvantages of the currently available anticancer drugs (3, 5-7).Diverse chemical structure containing 1,3,4-Thiadiazole have been reported with potential anticancer activity. Recently Maurizio Botta and coworkers reported the discovery of new derivatives of N-(5- (benzylthio)-1,3,4-thiadiazol-2-yl) benzamide as potent inhibitors of abl and src tyrosine kinases (14, 15). In the present study, we synthesized a new derivatives.the chemistry and pharmacology of [1,3,4] thiadiazole derivatives has been of great interest to medicinal chemists. Thiazoles containing N=C-S moiety has been employed as antipsychotic and antibacterial. Thiadiazole derivative particularly2-(4-methoxybenzyl)-6-phenyl-5-thiocyanatoimidazo[2,1- b][1,3,4]thiadiazole play vital role in pharmaceutical practice owing to their wide biological activities like fungicidal, antimicrobial, anti TB, anti cancer and anti-inflammatory. The title compound C 19 H 14 N 4 OS 2 was synthesized and structure was solved by X-ray crystallography. The final R-factor is for unique 3069 reflections with I >2σ(I). The cell parameters a = 6.117(2) Å, b= 7.47(4) Å, c = 18.25(3)Å, β =97.97(2) o. The molecular conformation is planar. Crystal packing is stabilized by weak C-H O interactions. The molecular geometry, mode of packing and the nature of he bonding will be discussed. Structure of 2-(4-methoxybenzyl)-6-phenyl-5-thiocyanatoimidazo[2,1-b][1,3,4]thiadiazole

2 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August We acknowledge the USIC at Karnatak University, Dharwad, for Bruker SMART APEX II Single Crystal XRD facility under DST- PURSE Programme. References: Bruker (2004). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Bruker (2010). APEX2 and SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA. Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. Flack, H. D. (1983). Acta Cryst. A39, Lynch, D. E., McClenaghan, I., Light, M. E. & Coles, S. J. (2002). Cryst. Eng. 5,

3 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August Lynch, D. E., Nicholls, L. J., Smith, G., Byriel, K. A. & Kennard, C. H. L. (1999). Acta Cryst. B55, Misra, R. N., Xiao, H.-Y., Kim, K. S., Lu, S., Han,W.-C., Barbosa, S. A., Hunt, J. T., Rawlins, D. B., Shan, W., Ahmed, S. Z., Qian, L., Chen, B.-C., Zhao, R., Bednarz, M. S., Kellar, K. A., Mulheron, J. G., Batorsky, R., Roongta, U., Kamath, A., Marathe, P., Ranadive, S. A., Sack, J. S., Tokarski, J. S., Pavletich, N. P., Lee, F. Y., Webster, K. R. & Kimball, S. D. (2004). J. Med. Chem. 47, Sheldrick, G. M. (2008). Acta Cryst. A64, Spek, A. L. (2009). Acta Cryst. D65, Supplementary Material: Phy_359_0m in P-1 P Crystal data a = (0.0002) alpha= 81.30(0.00) b = (0.0002) beta = 79.22(0.00) c = (0.0003) gamma= 75.03(0.00) V = ( 0.04) cubic-angstrom Niggli reduced cell: Niggli matrix: Transformation matrix: C 19. H 17. N 4. O 1. S 2. M = (Atomic weights 1977) Z = 2.00 D(calc.)= Mg/m3 F(000) = mu = cm-1 (Int.Tab. Vol.C, Table , p.193) Lambda = Angstrom Number of atoms: 41 Atomic coordinates Atom X/a Y/b Z/c S ( 11) ( 9) ( 6) S ( 14) ( 9) ( 7) O ( 35) ( 32) ( 19) N ( 33) ( 29) ( 18) N ( 37) ( 32) ( 20) N ( 34) ( 32) ( 19) N ( 36) ( 30) ( 18) C ( 54) ( 44) ( 30) H1A ( 0) ( 0) ( 0) H1B ( 0) ( 0) ( 0) H1C ( 0) ( 0) ( 0)

4 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August C ( 40) ( 38) ( 22) C ( 44) ( 39) ( 24) H ( 0) ( 0) ( 0) C ( 44) ( 41) ( 25) H ( 0) ( 0) ( 0) C ( 41) ( 36) ( 22) C ( 46) ( 39) ( 25) H6A ( 0) ( 0) ( 0) H6B ( 0) ( 0) ( 0) C ( 40) ( 35) ( 22) C ( 31) ( 27) ( 16) C ( 36) ( 35) ( 20) C ( 60) ( 48) ( 30) H ( 0) ( 0) ( 0) C ( 72) ( 56) ( 38) H ( 0) ( 0) ( 0) C ( 53) ( 54) ( 30) H ( 0) ( 0) ( 0) C ( 54) ( 45) ( 32) C ( 53) ( 56) ( 33) H ( 0) ( 0) ( 0) C ( 39) ( 33) ( 21) C ( 65) ( 64) ( 30) H ( 0) ( 0) ( 0) C ( 60) ( 51) ( 27) H ( 0) ( 0) ( 0) C ( 50) ( 41) ( 27) H ( 0) ( 0) ( 0) C ( 49) ( 45) ( 27) H ( 0) ( 0) ( 0) Orthogonal coordinates (Angstrom) Orthogonalization matrix: a b cosgamma c cosbeta b singamma -c sinbeta cosalpha c sinbeta sinalpha Atom X Y Z S (0.0009) (0.0007) (0.0008) S (0.0011) (0.0008) (0.0009) O (0.0029) (0.0027) (0.0026) N (0.0027) (0.0024) (0.0024) N (0.0031) (0.0027) (0.0027) N (0.0028) (0.0027) (0.0026) N (0.0030) (0.0025) (0.0024) C (0.0045) (0.0037) (0.0041) H1A (0.0000) (0.0000) (0.0000) H1B (0.0000) (0.0000) (0.0000) H1C (0.0000) (0.0000) (0.0000) C (0.0033) (0.0032) (0.0030) C (0.0037) (0.0032) (0.0033) H (0.0000) (0.0000) (0.0000) C (0.0037) (0.0034) (0.0034)

5 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August H (0.0000) (0.0000) (0.0000) C (0.0034) (0.0030) (0.0030) C (0.0038) (0.0032) (0.0034) H6A (0.0000) (0.0000) (0.0000) H6B (0.0000) (0.0000) (0.0000) C (0.0033) (0.0029) (0.0030) C (0.0026) (0.0022) (0.0022) C (0.0030) (0.0029) (0.0027) C (0.0050) (0.0040) (0.0041) H (0.0000) (0.0000) (0.0000) C (0.0060) (0.0047) (0.0052) H (0.0000) (0.0000) (0.0000) C (0.0045) (0.0045) (0.0041) H (0.0000) (0.0000) (0.0000) C (0.0045) (0.0037) (0.0043) C (0.0045) (0.0047) (0.0045) H (0.0000) (0.0000) (0.0000) C (0.0032) (0.0027) (0.0028) C (0.0054) (0.0053) (0.0041) H (0.0000) (0.0000) (0.0000) C (0.0050) (0.0042) (0.0037) H (0.0000) (0.0000) (0.0000) C (0.0041) (0.0034) (0.0037) H (0.0000) (0.0000) (0.0000) C (0.0041) (0.0037) (0.0037) H (0.0000) (0.0000) (0.0000) Displacement parameters, U(I,J)x104 exp(-2pi2(u11h2(a) u12hk(a)(b)+...) Atom U11 U22 U33 U23 U13 U12 S1 637( 5) 414( 4) 528( 4) -90( 3) -65( 3) -159( 3) S2 901( 7) 372( 4) 623( 5) -49( 3) -217( 4) -108( 4) O1 729( 15) 657( 15) 642( 14) -61( 11) 38( 12) -310( 12) N1 554( 13) 445( 12) 450( 12) -4( 9) -89( 10) -174( 10) N2 612( 15) 466( 13) 526( 13) -57( 10) -56( 11) -144( 11) N3 558( 14) 496( 13) 518( 14) -45( 10) -28( 11) -196( 11) N4 660( 15) 425( 12) 438( 12) -56( 9) -94( 11) -167( 10) C1 754( 22) 572( 19) 729( 22) -9( 16) -120( 18) -288( 17) H1A 1000( 0) H1B 1000( 0) H1C 1000( 0) C2 555( 16) 518( 15) 448( 14) -22( 11) -96( 12) -175( 12) C1 -H1C C1...N1 ( 1) H1C...N1 ( 1) C1 -H1C...N1 ( 1) 0.960(.004) 3.669(.005) 2.956(.002) ( 0.25) () C16 -H16 C16...O1 ( 2) H16...O1 ( 2) C16 -H16...O1 ( 2) 0.930(.005) 3.705(.005) 2.827(.003) ( 0.26) () Number of possible hydrogen bonds 5

6 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August () Values normalized following G.A.Jeffrey & L.Lewis, Carbohydr.Res. (1978).60,179; R.Taylor, O.Kennard, Acta Cryst.(1983).B39,133. Equivalent positions: ( 0) x,y,z ( 1) x,+y+1,+z ( 2) x,+y-1,+z+1 I hope that you succeeded in using this program and that the results of the calculations are useful to have a better understanding of your structure. Best wishes! Phy 359_0m in P-1 Sunday, 9 February 2014 at 12:04:34 SIR92 runs on: jt-vs Used commands & directives: %data Cell Space P -1 Content C 38 H 34 N 8 O 2 S 4 Rhomax Reflections jt-vs.hkl Format (3i4,2f8.0) Fosquare %normal %invariants %phase %fourier %export default default default default shelx jt-vs.res %end Files used in sir: Channel Name 1 card reader 2 line printer 30 direct access structure file jt-vs.bin 31 direct access scratch file

7 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August sequential scratch file 34 reflection input file jt-vs.hkl 41 scattering factors file c:\wingx\files\form.dat ( Release : ) 35 fourier peaks file jt-vs.ins 36 peaks file to be plotted jt-vs.plt 33 sequential scratch file w w w w w w w w w w w x w w w w w w w w w w w w w w w w w w w x w w w w w w w w y = s2

8 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August w x = ln <i> / sigfsq w ( w ) = wilson w ( ) = calc w w intercept = w slope = w b(iso) = w u(iso) = w scale = w scalef(obs.)2 = f(abs.) w Phy_359_0m in P-1 pseudotranslation section program searched for pseudo-translational symmetry no pseudo-translational symmetry has been found final statistics section distribution of <E2> with sin(theta)/lambda sinth/lam <E2> number average values average numeric graphic all data acentric centric hypercentric a. c. h. mod(e) E E E E E mod(e2-1) (E2-1) (E2-1) (mod(e2-1))

9 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August n(z) cumulative probability distribution z all data acentric centric hypercentric a. c. h distribution of E - number of E's.gt. limit E no number and percentage of F's > param sigma(f) number percentage 98% 98% 98% 97% 96% 96% 94% 93% 92% 91% param number and percentage of F's > limit number percentage 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% limit largest E-values to phase

10 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August SIR92 : Invariants routine Release Phy_359_0m in P Psi-zero relationships estimated among the 354 strongest and the 118 weakest reflections Negative quartets relationships estimated using 3002 psi-zero relationships Negative quartet s statistic Distribution of g - number of g's.gt. limit g no Sigma2 relationships estimated among the 354 strongest reflections - (Emin = 1.27) Triplet s statistic Distribution of g - number of g's.gt. limit g no triplets have been strengthened by 45 free vectors using p-10 formula Psi-e relationships among the 354 strongest and the 177 following reflections centrosymmetric, g(min) for psi-e = Insufficient psi-e found - lower g value and try again Psi-e relationships among the 354 strongest and the 177 following reflections Number of relationships Calculated stored Positive estimated triplets Negative estimated triplets enantiomorph sensitive triplets - - psi-zero triplets

11 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August psi-e triplets Negative estimated quartets enantiomorph sensitive quartets SIR92: Phase routine Release Phy 359_0m in P converge / diverge section Origin fixing reflexion(s) phase assigned code h k l E restriction phase , , , Selected symbols phase code h k l E restriction , , , , , Fourier recycling section Phy 359_0m in P ( 70% of total ) reflections used with Fo > 1.01 Step cycle residual A % A %

12 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August A % Intermediate interpretation Fragment n. 1,fused rings could be found around peaks Overall plot of the structure Projection on l.s.q. plane ---- scale: 2.50 cms/a

13 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August Fourier recycling restarted In step B scale factor, atomic coordinates and isotropic Thermal factors are refined via diagonal matrix. Step cycle residual B % B % B % B % Final interpretation Phy 359_0m in P-1

14 International Journal of Scientific & Engineering Research, Volume 5, Issue 8,August Assumed atomic parameters and limits for interatomic bonds and angles (Interspecies and intraspecies) Distances angles atomic user Type radius minimum maximum minimum maximum number conditions S O N C Tentative of peak labelling in terms of atomic species Group peaks possible species range of Number included chemical species assigned bond angles