Study on the esi mass spectra of a series of chelating platinum(II) complexes containing eugneol

110 HNUE JOURNAL OF SCIENCE DOI: 10.18173/2354-1059.2018-0078 Natural Sciences 2018, Volume 63, Issue 11, pp. 110-116 This paper is available online at STUDY ON THE ESI MASS SPECTRA OF A SERIES OF CHELATING PLATINUM(II) COMPLEXES CONTAINING EUGNEOL Truong Thi Cam Mai 1 , Tran Thi Hai 2 and Nguyen Thi Thanh Chi 3 1 Faculty of Chemistry, Quy Nhon University 2 Faculty of Chemistry, Graduate University of Sciences and Technology 3 Faculty of Chemistry, Hanoi National University of Education Abstract. The ESI mass spectra of ten platinum(II) complexes (P1-P10) bearing eugenol (EugH) were analyzed in detail. The result has established two unambiguous rules for the formation of pseudomolecular ions in the both positive-ion and negative-ion modes. Specifically, in the +ESI mass spectra the complexes bearing monodentate amine of the general formula [PtCl(Eug)(amine)] (P2-P8) tend to lose the amine ligands and combine together to create the neutral dimeric complex [Pt2Cl2(Eug)2]. Then the dimer complex is ionized in various ways to produce pseudomolecular ions [2M – 2Am - Cl]+, [2M – 2Am + H] + , or [2M – 2Am + H + solvent]+ (H can be replaced by Na or K). Whereas, in the -ESI mass spectra the complexes P2-P8 lost the amines to form the neutral monomer complex [PtCl(Eug)]. Then the monomer tends to combine with a Cl - ion or lose a H + ion to form pseudomolecular ions [M - Am + Cl] - or [M - Am - H] - . Keywords: Eugenol, amine, Pt(II) complexes, ESI-MS. 1. Introduction Eugenol (4-allyl-2-methoxyphenol), a natural bioactive compound, occupies large quantities of essential oils of some medicinal plants as clove (Syzygium aromaticum) and tulsi (Ocimum sanctum L.). Thus, eugenol is used in perfumery and flavoring industries, in formulating insect attractants, biocides, antiseptics, antifungal ect [1-4]. Recently, eugenol (EugH) and its derivatives as methyleugenol, alkyl eugenoxyacetate have been introduced into the coordination entity of platinum(II) in a series of complexes bearing arylolefin natural and amine [5-8]. Many of these complexes exhibit high anticancer activity on the tested human cancer cells [5-8]. In this study, the +/-ESI mass spectra of one of the series of complexes mentioned above, platinacyclic complexes containing eugenol and amine, are investigated to find out rules for formation of pseudomolecular ions in their spectra. Received November 12, 2018. Revised November 22, 2018. Accepted November 29, 2018. Contact Nguyen Thi Thanh Chi, e-mail address: chintt@hnue.edu.vn Study on the ESI mass spectra of a series of chelating platinum(II) complexes containing 111 2. Content 2.1. Experiments * Synthesis of complexes The complexes [Pt(µ-Cl)(Eug)]2 (P1), [PtCl(Eug)Am] (Am: ammonia (P2), p-chloroaniline (P3), p-toluidine (P4), piperidine (P5), pyridine (P6), 4-methylpyridine (P7), quinoline (P8)) and [Pt(Eug)(quinoline-8-olate)] (P9), [Pt(Eug)(2-methylquinoline-8-olate)] (P10) were synthesized according to the reference [7]. * Apparatus and methods The ESI mass spectra were recorded on an 1100 Series LC-MSD-Trap-SL at the Institute of Chemistry, Vietnam Academy of Science and Technology (for P2 ÷ P4 and P9) and Finnigan MAT LCQ at the Department of Chemistry, the National University of Singapore (for P1, P5 ÷ P8 and P10). 2.2. Results and discussion The complex [Pt(µ-Cl)(Eug)]2 (P1) was synthesized according to the method described in [7] with the yield of 40%. The interaction between P1 with the ammonia or aromatic and heterocyclic amines afforded complexes P2 ÷ P10 with yields of 50 ÷ 95%. The general reaction equation to synthesize P2 ÷ P10 is described in Scheme 1. Scheme 1: General reaction equation for the preparation of P2 ÷ P10 Am: ammonia (P2), p-chloroaniline (P3), p-toludine (P4), piperidine (P5), pyridine (P6), 4-methylpyridine (P7), quinoline (P8) The structures of P1 ÷ P10 were determined by using ESI mass, IR, NMR spectroscopies and single crystal X-ray diffraction [7]. In the present study, we analyze in detail their ESI mass spectra (one of the most effective methods for determining the composition and molecular formula at atmospheric pressure and moderate temperatures) in order to find out rules for formation of pseudomolecular ions in the positive and negative mode spectra. According to [9, 10], for ESI-MS method, process of transferring a sample solution into ions in gas phase undergoes three major steps. (i) Firstly, the sample solution is pumped through a high-voltage capillary tube, charged droplets are formed basing on a high electric field at the tip of the tube. (ii) The process of solvent evaporation occurs repeatedly under the effect of hot nitrogen to generate smaller electrically charged droplets. When Coulomb force of repulsion between the charges becomes stronger than the surface tension, the small droplets are broken into extremely small charged pieces and flow to the counter-electrode. (iii) By changing the electromagnetic field, the positive or negative ions are directed from the atmospheric pressure area to the vacuum and mass analyzer of the mass spectrometer. The spectrum of positive ions is denoted by + MS, the negative ion spectrum is denoted by -MS. At the end of the capillary tube, the ionization occurs in a variety of ways, depending on the recording condition and the relative stability of the sample. Truong Thi Cam Mai, Tran Thi Hai and Nguyen Thi Thanh Chi 112 The peak intensity of each ion depends on the corresponding ionic structure and is influenced by the solvent and the presence of the additives. Figure 1. Partial +ESI mass spectrum of [Pt(Eug)(2-methylquinoline-8-olate)] (P10) Complexes P1 ÷ P10 contain Pt and Cl elements which have many isotopes. Thus, the Mmin values are calculated with the 12 C, 1 H, 14 N, 194 Pt, 35 Cl, and 16 O isotopes, while the Mmax values are calculated with 13 C, 1 H, 14 N 198 Pt, 37 Cl and 16 O isotopes (Table 1). All the peaks with m/z are in the range of Mmin  Mmax belonging to the molecular ion peaks which correspond with different isotopics. And peaks with the highest intensity are used for determining the mass of the corresponding complex molecule (M) as presented in Table 1. Fig. 1 shows the +ESI mass spectrum of P10 as an example. (a) (b) Figure 2. Experimental isotopic pattern obtained by ESI-MS (a) and simulated isotopic pattern for [P10 + H] + fragment (b) The isotopic envelopes of the assigned peaks in Tables 1, 2 and 3 were compared with the calculated patterns by the Isotopeviewer software. The result indicates that they match with each other in terms of the number of peaks, the m/z value and the intensity of peaks. Figure 2 shows the experimental and simulated isotopic patterns of the [P10 + H] + fragment as an example. Study on the ESI mass spectra of a series of chelating platinum(II) complexes containing 113 Table 1. Molecular mass of P1 ÷ P10 determined by ESI mass spectroscopy, M (m/z: au) Comp. Molecular formula Mmin  Mmax Peak for determination of M (m/z, intensity) M P1 [PtCl(Eug)]2 784  816 [P1 + Na] + : 809/ 74 786 P2 [PtCl(Eug)(NH3)] 409  425 [2P2 - 2NH3 + H] + : 788/ 100 410 P3 [PtCl(Eug)(ClC6H4NH2)] 519  543 [2P3 - 2ClC6H4NH2 + H] + : 788/ 100 520 P4 [PtCl(Eug)(CH3C6H4NH2)] 499  522 [P4 - CH3C6H4NH2 + H] + : 607/ 100 499 P5 [PtCl(Eug)(C5H11N)] 472  492 [P5 + Na] + : 501/ 20 478 P6 [PtCl(Eug)(C5H5N)] 471  492 [P6 - Cl] + : 436/ 73 471 P7 [PtCl(Eug)(CH3C5H4N)] 485  506 [P7 - Cl] + : 450/ 68 485 P8 [PtCl(Eug)(C9H7N)] 521  546 [P8 - Cl] + : 487/ 26 522 P9 [Pt(Eug)(C9H6NO)] 501  525 [P9 + H] + : 503/ 100 502 P10 [Pt(Eug)(C10H8NO)] 515  539 [P10 + H] + : 517/ 98 516 Table 1 shows that the molecular mass value of the examined complexes is in the range of Mmin  Mmax. This means that the complexes have formula as expected. Tables 2 and 3 listed the main data in the +MS and -MS spectra of P1 ÷ P10 to find out rules for the ionization of the complexes. Table 2. Cations detected by +ESI mass spectroscopy (m/z, %) for complexes P1 ÷ P10 *: H is replaced by Na Assigned peaks Comp. m/z (au)/ intensity (%) [M + H] + [M - Cl] + [2M - 2Am + H] + Other ions P1 809/ 74 * - - [M - Cl + MeOH] + : 783/ 100 P2 - - 788/ 100 [2M - 2Am - Cl] + : 752/ 20 P3 - - 788/ 100 [2M - 2Am - Cl] + : 752/ 14 P4 - - 788/ 100 - P5 501/ 20 - [2M - 2Am + H + MeOH] + : 818/ 88 P6 - 436/ 73 - [2M - 2Am + Na] + : 810/ 80 P7 - 450/ 68 - [2M - 2Am + K] + : 826/ 100 [2M - 2Am + K + H2O] + : 844/ 45 P8 - 487/ 26 - [2M - 2Am + K + 2H2O] + : 862/ 100 P9 503/ 100 - - - P10 517/ 98 539/ 81 * - - [2M + Na] + : 1055/ 100 Truong Thi Cam Mai, Tran Thi Hai and Nguyen Thi Thanh Chi 114 Table 3. Anions detected by -ESI mass spectroscopy (m/z, %) for P1 ÷ P8 and P10 For P1, cations were formed by combining a Na + cation or losing a Cl - anion then receiving a MeOH molecule by P1 (Table 2). The formation of the analogous pseudomolecular ions were also observed in the +MS of [Pt2Cl2(PrEug)2] and [Pt2Cl2( i PrEug)2] [11, 12]. On the other hand, on the –ESI mass spectrum, the anions were formed by losing PtEug group, e.i. [PtCl2(Eug)] - ion, or combining a chlorine ion to form [Pt2Cl3(Eug)2] - ion (Table 3). The process of formation of [PtCl2(Eug)] - and [Pt2Cl3(Eug)2] - ions is described in Scheme 1. Scheme 1. The formation of the peaks [Pt2Cl3(Eug)2] - and [PtCl2(Eug)] - in -MS of P1 Table 2 and 3 show that two unambiguous rules for the formation of pseudomolecular ions in the mass spectra of P2 ÷ P10 have been established. Specifically, in the positive-ion mode the complexes P2 ÷ P8 bearing the monodentate amine tend to lose the amine ligand and combine together to create the neutral dimeric complex [Pt2Cl2(Eug)2] as describe in Scheme 2. Then the dimeric complex is ionized in various ways to produce ions [2M - 2Am - Cl] + , [2M - 2Am + H] + and [2M - 2Am + H + solvent] + (H can be replaced by Na or K) (Table 2). Meanwhile, in the - MS spectra the formation of this neutral dimeric complex was only observed in the spectra of P2 ÷ P4 (Table 2). In the negative-ion mode, the complexes P2 ÷ P8 lose the amine ligand to form the neutral monomer [PtCl(Eug)], then the monomer tends to combine with Cl - to form the pseudomolecular anions [M - Am + Cl] - , e.i. [PtCl2(Eug)] - with different intensities of 7-100% (for P2 ÷ P8) or lost H + to produce the anions [M - Am - H] - with quite strong intensities of 53- 100% (for P5 ÷ P8). Assigned peaks Comp. m/z (au)/ intensity (%) [M - Am - H] - [M - Am + Cl] - [2M - 2Am + Cl] - Other ions P1 - - - [M + Cl] - : 822/ 93 [M - (PtEug)] - : 429/ 100 P2 - 429/ 7 822/ 100 - P3 - 429/ 9 821/ 100 - P4 - 429/ 7 821/ 100 - P5 393/ 100 429/ 86 - - P6 393/ 53 429/ 100 - [2M - Am + Cl] - : 913/ 15 P7 393/ 75 429/ 73 - [2M - Am + Cl] - : 913/ 17 P8 391/60 429/ 55 - - Study on the ESI mass spectra of a series of chelating platinum(II) complexes containing 115 Scheme 2. Formation of the dimeric complex P1 from P2 ÷ P8 Unlike P2 ÷ P8, the complexes P9 and P10 containing the chelating ligand (quinoline-8- olate, 2-methylquinoline-8-olate) have no tendency to create the neutral dimer in the +ESI mass spectra but form pseudomolecular cations [M + H] + or [M + Na] + with the strong intensities of 81-100%. And they appeared to be unstable and difficult to ionize in the –ESI mass spectra. 3. Conclusions In this paper, the ESI mass spectra of a series of platinum(II) complexes bearing eugenol (EugH) of the general formula [PtCl(Eug)Am] (P2-P8), Pt(Eug)(RQui-O)] (P9, P10) and [Pt(µ- Cl)(Eug)]2 (P1) were studied. The result shows that not only the component and molar mass of the complexes have been elucidated being in good agreement with the expected ones but also the two unambiguous rules have been established. Specifically, the complexes bearing the monodentate amine (P2 ÷ P8) lose the amine ligand to create the dimer complex [Pt2Cl2(Eug)2] in the +ESI mass spectra or the monomer complex [PtCl(Eug)] in the –ESI mass spectra. Then the monomer tends to combine with a Cl - ion or lose a H + ion to form pseudomolecular ions [M - Am + Cl] - or [M - Am - H] - while the dimer tends to form pseudomolecular ions [2M – 2Am - Cl]+, [2M – 2Am + H] + , or [2M – 2Am + H + solvent]+ (H can be replaced by Na or K). These rules will facilitate for assignment ESI mass spectra of analogous platinum(II) complexes. Acknowledgements. This research is funded by the Vietnam Ministry of Education and Training under the grant number B2017-DQN-04. REFERENCES [1] Pramod, K., Ansari, S. H., & Ali, J., 2013. Development and validation of UV spectrophotometric method for the quantitative estimation of eugenol. Asian Journal of Pharmaceutical Analysis, 3(2), 58-61. [2] Chami, F., Chami, N., Bennis, S., Trouillas, J., & Remmal, A., 2004. Evaluation of carvacrol and eugenol as prophylaxis and treatment of vaginal candidiasis in an immunosuppressed rat model. Journal of antimicrobial chemotherapy, 54(5), 909-914. [3] Prakash, P., & Gupta, N., 2005. Therapeutic uses of Ocimum sanctum Linn (Tulsi) with a note on eugenol and its pharmacological actions: a short review. Indian journal of physiology and pharmacology, 49(2), 125. [4] Darshan, S., & Doreswamy, R., 2004. Patented antiinflammatory plant drug development from traditional medicine. Phytother. Res., 18(5), 343-357. Truong Thi Cam Mai, Tran Thi Hai and Nguyen Thi Thanh Chi 116 [5] Tran Thi Da, Young-Mi Kim, Truong Thi Cam Mai, Nguyen Cao Cuong, Nguyen Huu Dinh, 2010. Mono - and dinuclear metallacyclic complexes of Pt(II) synthesized from some eugenol derivatives. J. Coord. Chem., 63, 473-483. [6] Tran Thi Da, Le Thi Hong Hai, Luc Van Meervelt, Nguyen Huu Dinh, 2015. Synthesis structure and in vitro cytotoxicity of organoplatinum(II) complexes containing aryl olefins and quinolines. J. Coord. Chem., 68, 3525-3536. [7] Nguyen Thi Thanh Chi, Tran Thi Da, Koen Robeyns, Luc Van Meervelt, Truong Thi Cam Mai, Nguyen Dang Dat and Nguyen Huu Dinh, 2018. Synthesis, crystal and solution structure of platinacyclic complexes containing eugenol, the main bioactive constituent of Ocimum sanctum L. Oil. Polyhedron, 151, 330-337. [8] Nguyen Thi Thanh, C., Pham Van, T., Truong Thi Cam, M. & Van Meervelt, L., 2018. Mixed natural arylolefin-quinolines platinum(II) complexes: Synthesis, structural characterization and in vitro cytotoxicity studies. Acta Cryst., C74. Doi: 10.1107/S2053229618015978. [9] Ho C. S., Lam C. W. K, Chan M.H.M, Cheung R. C .K, Law L. K., Lit L. C. W, Suen M. W. M. and Tai H. L., 2003. Electrospray Ionization Mass Spectrometry: Principles and Clinical Applications, Clin. Biochem. Rev., 24(1), 3-12. [10] Andries P. Bruins, 1998. Mechanistic aspects of electrospray ionization. Journal of Chromatography A, 794, 345–357. [11] Pham Van Thong, Nguyen Thi Thanh Chi, 2014. Study on the synthesis and structure of two complexes K[PtCl3(isopropyl eugenoxyacetate)] and [PtCl2(isopropyl eugenoxyacetate- 1H)]2. Vietnam Journal of Chemistry, 52(3), 381-386. [12] Nguyen Thi Thanh Chi, Truong Thi Cam Mai, Nguyen Thi Thanh Nhan, Tran Thi Da, 2013. Study on the synthesis and structure of the monoplatinum(II) and diplatinum(II) complexes bearing propyl eugenoxyacetate. Vietnam Journal of Chemistry, 51, 500-504.