Induced in-source fragmentation pattern of certain novel (1Z,2E)-N-(aryl)propanehydrazonoyl chlorides by electrospray mass spectrometry (ESI-MS/MS)

Chemistry Central Journal

Ali S Abdelhameed¹  Mohamed W Attwa¹  Hatem A Abdel-Aziz¹  Adnan A Kadi¹ 

[1] Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia

关键词: Electrospray ionization;    Fragmentor voltage;    Hydrazones;    In-source fragmentation;   

Others  :  787976
DOI  :  10.1186/1752-153X-7-16

 received in 2012-11-11, accepted in 2013-01-23,  发布年份 2013

【 摘 要 】

Background

Collision induced dissociation (CID) in the triple quadrupole mass spectrometer system (QQQ) typically yields more abundant fragment ions than those produced with resonance excitation in the presence of helium gas in the ion trap mass spectrometer system (IT). Detailed product ion spectra can be obtained from one stage MS² scan using the QQQ. In contrast, generating the same number of fragment ions in the ion trap requires multiple stages of fragmentation (MSⁿ) using CID via in-trap resonance excitation with the associated time penalties and drop in sensitivity.

Results

The use of in-source fragmentation with electrospray ionization (ESI) followed by product ion scan (MS²) in a triple quadrupole mass spectrometer system, was demonstrated. This process enhances the qualitative power of tandem mass spectrometry to simulate the MS³ of ion trap for a comprehensive study of fragmentation mechanisms. A five pharmacologically significant (1Z, 2E)-N-arylpropanehydrazonoyl chlorides (3a-e) were chosen as model compounds for this study. In this work, detailed fragmentation pathways were elucidated by further dissociation of each fragment ion in the ion spectrum, essentially, by incorporating fragmentor voltage induced dissociation (in-source fragmentation) and isolation of fragments in a quadrupole cell Q1. Subsequently, CID occurs in cell, Q2, and fragment ions are analyzed in Q3 operated in product ion mode this process can be referred to as pseudo-MS³ scan mode.

Conclusions

This approach allowed unambiguous assignment of all fragment ions using tandem mass spectrometer and provided adequate sensitivity and selectivity. It is beneficial for structure determination of unknown trace components. The data presented in this paper provide useful information on the effect of different substituents on the ionization/fragmentation processes and can be used in the characterization of this important class of compounds.

【 授权许可】

   
2013 Abdelhameed et al; licensee Chemistry Central Ltd.

【 图 表 】

Scheme 1

Figure 1.

Figure 2.

Scheme 2

Figure 3.

【 参考文献 】

• [1]Kawasaki N, Ohta M, Hyuga S, Hashimoto O, Hayakawa T: Analysis of carbohydrate heterogeneity in a glycoprotein using liquid chromatography/mass spectrometry and liquid chromatography with tandem mass spectrometry. Anal Biochem 1999, 269:297.
• [2]Krahmer MT, Johnson YA, Walters JJ, Fox KF, Fox A, Nagpal M: Electrospray quadrupole mass spectrometry analysis of model oligonucleotides and polymerase chain reaction products: determination of base substitutions, nucleotide additions/deletions, and chemical modifications. Anal Chem 1999, 71:2893.
• [3]Kapur A, Beck JL, Sheil MM: Observation of daunomycin and nogalamycin complexes with duplex dna using electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 1999, 13:2489.
• [4]Mo W, Sakamoto H, Nishikawa A, Kagi N, Langridge JI, Shimonishi Y, Takao T: Structural characterization of chemically derivatized oligosaccharides by nanoflow electrospray ionization mass spectrometry. Anal Chem 1999, 71:4100.
• [5]Risberg A, Masoud H, Martin A, Richards JC, Moxon ER, Schweda EKH: Structural analysis of the lipopolysaccharide oligosaccharide epitopes expressed by a capsule-deficient strain of Haemophilus influenzae Rd. Eur J Biochem 1999, 261:171.
• [6]Lhoëst G, Zey T, Verbeeck RK, Wallemacq P, Maton N, DeHoux JP, Latinne D: Isolation from pig liver microsomes, identification by electrospray tandem mass spectrometry and in vitro immunosuppressive activity of a rapamycin tris-epoxide metabolite. J Mass Spectrom 1999, 34:28.
• [7]Castillo M, Alonso MC, Riu J, Barcelo D: Identification of polar, ionic, and highly water soluble organic pollutants in untreated industrial wastewaters. Environ Sci Technol 1999, 33:1300.
• [8]Magnuson ML, Urbansky ET, Kelty CA: Determination of perchlorate at trace levels in drinking water by ion-pair extraction with electrospray-mass spectrometry. Anal Chem 2000, 72:25.
• [9]Mauri D, Migliazza B, Pietta P: Liquid chromatography/electrospray mass spectrometry of bioactive terpenoids in Ginkgo biloba L. J Mass Spectrom 1999, 34:1361.
• [10]Putschew A, Jekel M: Induced in-source fragmentation for the selective detection of organic bound iodine by liquid chromatography/electrospray mass spectrometry. Rapid Commun Mass Spectrom 2003, 17:2279.
• [11]Huetteroth A, Putschew A, Jekel M: Selective detection of unknown organic bromine compounds and quantification potentiality by negative-ion electrospray ionization mass spectrometry with induced in-source fragmentation. Int J Environ Anal Chem 2007, 87:415.
• [12]Gil JH, Hong J, Choe JC, Kim YH: Analysis of fatty acyl groups of diacyl galactolipid molecular species by HPLC/ESI-MS with in-source fragmentation. Bull Korean Chem Soc 2003, 24:1163.
• [13]Tian Q, Duncan CJG, Schwartz SJ: Atmospheric pressure chemical ionization mass spectrometry and in-source fragmentation of lutein esters. J Mass Spectrom 2003, 38:990-995.
• [14]Carrier DJ, Eckers C, Wolff J-C: In-source” fragmentation of an isobaric impurity of lamotrigine for its measurement by liquid chromatography tandem mass spectrometry after pre-concentration using solid phase extraction. J Pharm Biomed Anal 2008, 47:731.
• [15]Yan Z, Caldwell GW, Jones WJ, Masucci JA: Cone voltage induced in-source dissociation of glucuronides in electrospray and implications in biological analyses. Rapid Commun Mass Spectrom 2003, 17:1433.
• [16]Van Berkel GJ, Mcluckey SA, Glish GL: Electrospray ionization of porphyrins using a quadrupole ion trap for mass analysis. Anal Chem 1991, 63:1098.
• [17]Loo JA, Udseth HR, Smith RD: Collisional effects on the charge distribution of ions from large molecules, formed by electrospray-ionization mass spectrometry. Rapid Commun Mass Spectrom 1988, 2:207.
• [18]Bure C, Gobert W, Lelievre D, Delmas A: In-source fragmentation of peptide aldehydes and acetals: influence of peptide length and charge state. J Mass Spectrom 2001, 36:1149.
• [19]Weinmann W, Stoertzel M, Vogt S, Wendt J: Tune compounds for electrospray ionisation/in-source collision-induced dissociation with mass spectral library searching. J Chromatogr A 2001, 926:199.
• [20]Zhang M-Y, Pace N, Kerns EH, Kleintop T, Kagan N, Sakuma T: Hybrid triple quadrupole-linear ion trap mass spectrometry in fragmentation mechanism studies: application to structure elucidation of buspirone and one of its metabolites. J Mass Spectrom 2005, 40:1017.
• [21]Hopfgartner G, Husser C, Zell M: Rapid screening and characterization of drug metabolites using a new quadrupole–linear ion trap mass spectrometer. J Mass Spectrom 2003, 38:138.
• [22]Abdel-Aal MT, El-Sayed WA, El-Ashry EH: Synthesis and antiviral evaluation of some sugar arylglycinoylhydrazones and their oxadiazoline derivatives. Arch Pharm Chem Life Sci 2006, 339:656.
• [23]Brouwer WG, Osika EM: Anti-viral aromatic hydrazones. United States Patent number 5914351 1999. Filed: 12 December 1997, Issued: 22 June 1999
• [24]Abdel-Aziz HA, Abdel-Wahab BF, Badria FA: Stereoselective synthesis and antiviral activity of (1E,2Z,3E)-1-(Piperidin-1-yl)-1-(arylhydrazono)-2-[(benzoyl/benzothiazol-2-oyl)hydrazono]-4-(aryl1)but-3-enes. Arch Pharm Chem Life Sci 2010, 343:152.
• [25]Abdel-Aziz HA, Mekawey AAI: Stereoselective synthesis and antimicrobial activity of benzofuran-based (1E)-1-(piperidin-1-yl)-N2-arylamidrazones. Eur J Med Chem 2009, 44:4985.
• [26]Frohberg P, Kupfer C, Stenger P, Baumeister U, Nuhn P: Lipoxygenase-inhibitoren, 4. Mitt.: synthese und cyclisierungsreaktionen offenkettiger N1-arylsubstituierter amidrazone (pages 505–516). Arch Pharm 1995, 328:505.
• [27]Debord J, N’Diaye P, Bollinger JC, Fikri K, Penicaut B, Robert JM, Robert PS, Le-Baut G: Cholinesterase inhibition by derivatives of 2-amino-4,6-dimethylpyridine. J Enzyme Inhib Med Chem 1997, 12:13.
• [28]El Ashry ESH, Rashed NA, Shobier HS: Glycosidase inhibitors and their chemotherapeutic value, part 3. Pharmazie 2000, 55:403.
• [29]Robert JM, Rideau O, Piessard SR, Duflos M, Le-Baut G, Grimaud N, Juge M, Petit JY: Synthesis and anti-inflammatory activity of polyazaheterrocyclic derivatives of 6-amino-2,4-lutidine and their precursors. Arzneimittel-Forschung/Drug Research 1997, 47:635.
• [30]Mamolo MG, Falagiani V, Vio L, Banfi E: Synthesis and antimycobacterial activity of some N1-[1-[3-aryl-1-(pyridin-2-, 3-, or 4-yl)-3-oxo]propyl]-2-pyridinecarboxamidrazones. IL Farmaco 1999, 54:761.
• [31]Ranft D, Lehwark-Yvetot G, Schaper K, Buge A: N1-hetaryl substituted pyridine- and pyrazinecarboxamidrazones with antimycobacterial activity. Arch Pharm 1997, 330:169.
• [32]Ranft D, Seyfarth T, Schaper K, Lehwark-Yvetot G, Bruhn C, Buge A: New N1-hetarylmethylene-substituted amidrazones with potential antimycobacterial activity. Arch Pharm 1999, 332:427.
• [33]Davies EP, Pittam JD, Mallion KB, Taylor NP: Process for preparing an antifungal azole with hydrazino and amidrazone intermediates. United States Patent number 5861516 1999. Filed: 9 April, 1997, Issued: 19 January 1999
• [34]Drutkowski G, Donner C, Schulze I, Frohberg P: Derivatives of arylhydrazonic acids. Part 2: a facile approach to novel 4,5-dihydro-1 H-1,2,4-triazoles via cyclization of amidrazones. Tetrahedron 2002, 58:5317.
• [35]Frohberg P, Wagner C, Meier R, Sippl W: Derivatives of arylhydrazonic acids. Part 3: stereochemical rearrangement of Z-oxanilo-N1-dialkyl-N2-arylamidrazones. Tetrahedron 2006, 62:6050.
• [36]Modzelewska-Banachiewicz B, Matysiak J, Niewiadomy A: Synthesis and mycological activity of the compounds obtained in the reaction of N3-substituted amidrazones with sulphinyl-bis-2,4-dihydroxybenzenethioyl. Eur J Med Chem 2001, 36:75.
• [37]Cocco MT, Congiu C, Lilliu V, Onnis V: Amidrazones as precursors of biologically active compounds – synthesis of diaminopyrazoles for evaluation of anticancer activity. Arch Pharm 2006, 339:7-13.
• [38]El Kaim L, Grimaud L, Jana NK, Mettetal F, Tirla C: Amines addition to alpha-nitrohydrazones: application to amidrazones and triazoles formation. Tetrahedron Lett 2002, 43:8925.