Study of Diketone/Metal Ion Complexes by Electrospray Ionization Mass Spectrometry: Influence of Keto-Enol Tautomerism and Chelation

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Brad J. Hall and Jennifer S. Brodbelt Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas, USA

The formation and collisionally activated dissociation (CAD) behavior of a series of complexes containing cyclic or linear diketone ligands and alkali, alkaline earth, or transition metal ions are investigated. Electrospray ionization (ESI) is utilized for introduction of the metal ion complexes into a quadrupole ion trap mass spectrometer. The proximity of the carbonyl groups is crucial for formation and detection of ion complexes by ESI. For example, no metal ion complexes are observed for 1,4-cyclohexanedione, but they are readily detected for the isomers, 1,2- and 1,3-cyclohexanedione. Although the diketones form stable doubly charged ϩ complexes, the formation of singly charged alkaline earth complexes of the type (nL ϩ M2 Ϫ ϩ ϩ H ) where L ϭ 1,3-cyclohexanedione or 2,4-pentanedione is the first evidence of charge reduction. CAD investigations provide further evidence of charge reduction processes occurring in the gas-phase complexes. The CAD studies indicate that an intramolecular proton transfer between two diketone ligands attached to a doubly charged metal ion, followed by elimination of the resulting protonated ligand, produces the charge reduced complex. For transition metal complexation, the preference for formation of doubly charged versus singly charged complexes correlates with the keto-enol distribution of the diketones in solution. (J Am Soc Mass Spectrom 1999, 10, 402–413) © 1999 American Society for Mass Spectrometry

he coordination chemistry of ␤-diketones, com- metal-coordinated ions observed by ESI-MS may be pounds that exist in both enol and keto forms, has compared to complexes studied by other techniques Tbeen extensively studied in solution over several such as nuclear magnetic resonance spectroscopy decades [1–7]. Loss of a proton from a diketone results (NMR) or electrochemistry. In other situations, how- in the formation of a highly reactive diketonate that ever, the detection and identification of charged com- may act as an excellent chelating agent. From one to plexes by ESI-MS represents the exploration of new three diketonate molecules may react with a metal ion solution chemistry [8], not yet substantiated by other to produce a diverse array of metal complexes, and both analytical techniques. The process of transferring ions the selectivity of complex formation and stability of the from the solution to the gas phase by electrospray resulting complexes in solution have been investigated ionization (ESI) is believed to be gentle enough so that in detail by numerous methods [1–7]. Because of the the ions observed in the mass spectrum in many cases strong coordination capabilities of ligands containing reflect the species present in the solution [19]. negatively charged oxygen groups, there has also been Growing interest has focused on the exploration of great interest in incorporating such donor groups into metal–ligand interactions in the gas phase [8, 20, 21], in molecules designed for specific purposes [3, 7], such as part because of the development of methods to generate for extraction of selected metal ions from solution. Little and study multiligated metal complexes of increasing is known about the gas-phase coordination chemistry of complexity and specificity. The study of complexes in diketonates due to the inability to generate such com- which several ligands are bound to a metal ion may plexes by conventional ionization methods. However, shed light into the existence and understanding of in the past few years electrospray ionization mass intermolecular interactions within these complexes. In spectrometry (ESI-MS) has been demonstrated as a this respect, electrospray ionization has greatly ex- novel tool for the study of a variety of metal coordina- panded the range of studies possible involving metal tion complexes [8–18]. In some cases the identity of complexes because both singly and multiply charged species can be transferred into the gas phase for subse- quent characterization. Address reprint requests to Dr. Jennifer S. Brodbelt, The University of Texas at Austin, Department of Chemistry and Biochemistry, Austin, TX 78712- Recent reports of multiligated metal ions in the gas 1167. E-mail: [email protected] phase have shown that the first bonds formed to the

© 1999 American Society for Mass Spectrometry. Published by Elsevier Science Inc. Received December 4, 1998 1044-0305/99/$20.00 Revised January 12, 1999 PII S1044-0305(99)00002-1 Accepted January 12, 1999 J Am Soc Mass Spectrom 1999, 10, 402–413 DIKETONE/METAL ION COMPLEXES 403 metal ion are the strongest [15–18, 22–24]. For example, for alkali metal ion complexes the first two monoden- tate ligands, such as dimethyl ether molecules, are each bound by about 20–25 kcal/mol, whereas the third and fourth are each bound by about 15 kcal/mol [22]. The ϩ bond energies for complexes involving Li , a smaller ϩ ion than Na , are greater than the bond energies of the ϩ Na complexes because of the greater charge density of ϩ the Li ion. However, ligand repulsions become more ϩ severe in the Li complexes as additional ligands are added due to the greater extent of crowding, thus counteracting the enhanced binding energies stemming from the charge density effect [22]. From a study of several singly charged transition metal ions, it was found that the first two water molecules are each bound by about 15–20 kcal/mol [23, 24]. As the metal ion becomes more crowded, the degree of ligand–ligand repulsions increases and the charge becomes more delocalized. The general trends for alkali metal vs. transition metal complexation are similar, although there are less restrictions for how the ligands are positioned in the alkali metal complexes because the alkali metal ions do not have specific binding geometries as do the transition metal ions. In an investigation of the binding energies of complexes with doubly charged transition metal ions and water molecules, it was found that the binding energies were about 15 kcal/mol for each of the water molecules beyond the first seven [15]. The first six water molecules were each bound by 60 kcal/mol to the doubly charged metal ions, as expected due to the much higher charge densi- Figure 1. Structures of compounds in study. ties of doubly vs. singly charged metal ions. These previous reports have clearly shown that metal coordi- plexes containing more complicated ligands, such as nation complexes are stable, strongly bound species in ones that chelate metals. the absence of solvent. In the work presented here, the positively charged Collisionally activated dissociation (CAD) has re- complexes of a series of diketones (Figure 1) with a cently been used to probe the fragmentation pathways variety of metal species are studied. Emphasis is placed of multiligated metal complexes containing doubly on exploration of the type of complexes observed by charged metal ions [15–18, 25]. Although disassembly ESI-MS and further evaluation of these ions through by losses of the ligands is a predominant reaction, CAD. Differences in complex formation between cyclic, evidence for charge reduction has also been found. In linear, and aromatic diketones with metals from the some of the earliest studies, Kebarle et al. observed the alkali, alkaline earth, and transition families are dis- formation of singly charged complexes upon activation ϩ cussed in detail with respect to the keto-enol distribu- of M2 (H O) complexes where M ϭ Mg, Ca, Ni, or Co 2 n tion and chelating properties of the ligands. [15, 16]. The reduction process involved an intermolecular proton transfer between two water molecules, ϩ resulting in elimination of H3O and leaving a unit of Experimental hydroxide bound to the metal ion. In Leary’s recent Electrospray Ionization studies, reduction of the metal ion was observed upon CAD of doubly charged metal complexes containing Experiments were performed by using a Finnigan MAT acetonitrile, pyridine, or methanol ligands [17, 18]. In ion trap mass spectrometer operating in the mass-selective some cases, the metal actually underwent reduction via ionization mode with modified electronics to allow for electron transfer from one of the ligands to the metal ion axial modulation. The electrospray interface is based on a depending on the ionization potentials of the species design reported by the Oak Ridge ion trap group [26]. involved. In other cases, the resulting complex was Solutions were pumped at a rate of 2–5 ␮L/min by a reduced based on a proton transfer from one of the Harvard Apparatus 22 syringe pump (Harvard Appara- ligands to another, similar to the process observed by tus, Holliston, MA). The interface was pumped to a Ϫ Kebarle. These previous studies have established a pressure of 3.7 ϫ 10 1 torr, whereas the chamber was Ϫ framework for additional studies of multiligated com- maintained at a nominal pressure of 5 ϫ 10 5 torr. 404 HALL AND BRODBELT J Am Soc Mass Spectrom 1999, 10, 402–413

Table 1. ESI and CAD results for diketones with alkali metalsa Na K Rb Cs

Compound % Ion CAD % Ion CAD % Ion CAD % Ion CAD

1,2-Cyclohexanedione 100 (L ϩ Naϩ) NPD 100 (L ϩ Kϩ) Ϫ112 100 (L ϩ Rbϩ) Ϫ112 100 (L ϩ Csϩ) Ϫ112 (mw 112) 1,3-Cyclohexanedione 90 (L ϩ Naϩ) NPD 90 (L ϩ Kϩ) Ϫ112 100 (L ϩ Rbϩ) Ϫ112 100 (L ϩ Csϩ) Ϫ112 (mw 112) 10 (2L ϩ Naϩ) Ϫ112 10 (2L ϩ Kϩ) Ϫ112 1,4-Cyclohexanedione ND ND ND ND (mw 112) 2,3-Pentanedione 50 (2L ϩ Naϩ) NPD 50 (2L ϩ Kϩ) Ϫ200 50 (2L ϩ Rbϩ) Ϫ200 50 (2L ϩ Csϩ) Ϫ200 (mw 100) 50 (3L ϩ Naϩ) Ϫ100 50 (3L ϩ Kϩ) Ϫ300 50 (3L ϩ Rbϩ) Ϫ300 50 (2L ϩ Csϩ) Ϫ300 2,4-Pentanedione 100 (L ϩ Naϩ) NPD 100 (L ϩ Kϩ) Ϫ100 100 (L ϩ Rbϩ) Ϫ100 100 (L ϩ Csϩ) Ϫ100 (mw 100) 2,5-Hexanedione Ͼ95 (L ϩ Naϩ) NPD 100 (L ϩ Kϩ) Ϫ114 100 (L ϩ Rbϩ) Ϫ114 100 (L ϩ Csϩ) Ϫ114 (mw 114) Ͻ5 (2L ϩ Naϩ) Ϫ114 aNPD ϭ no CAD product detected. ND ϭ no adducts detected.

A positive voltage of 3.0–3.5 kV was applied to the event by mixing four parts ligand with one part metal needle, and ions were injected through a 100-mm for all of the ligand–metal systems except the alkali diameter sampling orifice, typically maintained at 100– metal complexes which were generated by adding one 120 V. Ions were then focused by a series of lenses part ligand to one part metal. These mixtures were through a seven-hole endcap electrode into the ion trap diluted with an additional four parts methanol prior to for storage, manipulation, and detection. Ions were loading the syringe. gated into the ion trap for each scan at injection times ranging between 25 and 100 ms. The isolation and Results and Discussion fragmentation of the ions were accomplished by using a Stored Waveform Inverse Fourier Transform (SWIFT) The electrospray process involves ionization and trans- system described elsewhere [27]. Fragmentation of the port of species formed in solution to the gas phase [19]. ions was accomplished by applying an ac voltage During the ESI period, some complexes are unstable between 200 and 600 mV on both endcaps of the ion and will not survive the desolvation process, some will trap for a period of 20 ms. These activation conditions convert to other products, and some will not be resulted in low energy, multiple collisions with helium charged, thus preventing their detection by the mass as the target. Ions were detected by using a Channeltron spectrometer. For the electrospray ionization of metal/ 4773 electron multiplier detector (Galileo Electro-Op- diketone solutions, complexes containing two diketo- tics, Sturbridge, MA). nate ligands and a doubly charged metal ion or one diketonate ligand and a singly charged metal ion will Reagents have no net charge and thus can not be monitored. This charge dependence means that certain types of ions nat- All diketones and quinones were obtained from Aldrich urally formed in solution are not amenable to ESI analysis, Chemical (Milwaukee, WI) except 9,10-phenan- but other types of novel complexes that are not routinely threnequinone, which was obtained from Fluka Chemi- monitored in solution may emerge in the ESI process. ka–Biochemika (Ronkonkoma, NY). Cobalt bromide, nickel bromide, copper bromide, rubidium bromide, Formation of Alkali Metal/Diketone Complexes and cesium iodide were also obtained from Aldrich Chemical. Magnesium chloride and calcium chloride Alkali metal complexation was studied first because alkali were purchased from Spectrum Chemical (Gardena, metal ions engage in weak, nonspecific electrostatic inter- CA). Sodium chloride, potassium chloride, and barium actions with organic ligands. Upon ESI of methanolic chloride were obtained from EM Science (Gibbstown, solutions containing alkali metals with diketones or qui- NJ). Strontium nitrate was purchased from J.T. Baker nones, the most predominant trend is the formation of (McGaw Park, IL). All reagents were used without singly charged monomer and/or dimer complexes. Tables further purification. 1 and 2 summarize the complexes detected along with Stock solutions of the diketones and quinones were their relative abundance and fragments found upon CAD Ϫ prepared at 5 ϫ 10 3 M in analytical grade methanol. for the diketone and quinone complexes, respectively. All stock metal salt solutions were also prepared at 5 ϫ Singly charged complexes for most of the ligands were Ϫ 10 3 M in analytical grade methanol, first dissolving in easily observed in the mass spectrometer, however the 1–3 mL of deionized water if necessary before dissolu- signals of the complexes with 1,2-cyclohexanedione and tion with methanol. Complexes of a particular ligand 2,3-pentanedione and the alkali metals were relatively and metal were prepared just prior to the electrospray weak compared to the other ligands studied. The sig- J Am Soc Mass Spectrom 1999, 10, 402–413 DIKETONE/METAL ION COMPLEXES 405

Table 2. ESI and CAD results for 1,2-napthoquinone and 9,10-phenanthrenequinone with alkali, alkaline earth, and transition metals 1,2-Naphthoquinone 9,10-Phenanthrenequinone

Metal % Ion CAD % Ion CAD

Sodium 60 (L ϩ Naϩ) NPD 45 (L ϩ Naϩ) NPD 40 (2L ϩ Naϩ)(Lϩ Naϩ) 55 (2L ϩ Naϩ)(Lϩ Naϩ) Potassium 65 (L ϩ Kϩ) NPD 40 (L ϩ Kϩ) NPD 35 (2L ϩ Kϩ)(Lϩ Kϩ) 60 (2L ϩ Kϩ)(Lϩ Kϩ) Rubidium 70 (L ϩ Rbϩ)Rbϩ 75 (L ϩ Rbϩ)Rbϩ 30 (2L ϩ Rbϩ)(Lϩ Rbϩ) 25 (2L ϩ Rbϩ)(Lϩ Rbϩ) Cesium 95 (L ϩ Csϩ)Csϩ 80 (L ϩ Csϩ)Csϩ 5 (2L ϩ Csϩ)(Lϩ Csϩ) 20 (2L ϩ Csϩ)(Lϩ Csϩ) Magnesium 70 (3L ϩ Mg2ϩ) (2L ϩ Mg2ϩ) 80 (3L ϩ Mg2ϩ) (2L ϩ Mg2ϩ) 30 (4L ϩ Mg2ϩ) (3L ϩ Mg2ϩ) 20 (4L ϩ Mg2ϩ) (3L ϩ Mg2ϩ) Calcium 20 (3L ϩ Ca2ϩ) (2L ϩ Ca2ϩ) 5 (3L ϩ Ca2ϩ) (2L ϩ Ca2ϩ) 80 (4L ϩ Ca2ϩ) (3L ϩ Ca2ϩ) 90 (4L ϩ Ca2ϩ) (3L ϩ Ca2ϩ) 5 (5L ϩ Ca2ϩ) (4L ϩ Ca2ϩ) Strontium 15 (3L ϩ Sr2ϩ) (2L ϩ Sr2ϩ) 20 (3L ϩ Sr2ϩ) (2L ϩ Sr2ϩ) 70 (4L ϩ Sr2ϩ) (3L ϩ Sr2ϩ) 40 (4L ϩ Sr2ϩ) (3L ϩ Sr2ϩ) 15 (5L ϩ Sr2ϩ) (4L ϩ Sr2ϩ) 40 (5L ϩ Sr2ϩ) (4L ϩ Sr2ϩ) Barium 20 (3L ϩ Ba2ϩ) (2L ϩ Ba2ϩ) 10 (3L ϩ Ba2ϩ) (2L ϩ Ba2ϩ) 40 (4L ϩ Ba2ϩ) (3L ϩ Ba2ϩ) 10 (4L ϩ Ba2ϩ) (3L ϩ Ba2ϩ) 40 (5L ϩ Ba2ϩ) (4L ϩ Ba2ϩ) 80 (5L ϩ Ba2ϩ) (4L ϩ Ba2ϩ) Cobalt 100 (3L ϩ Co2ϩ) (2L ϩ Co2ϩ) 100 (3L ϩ Co2ϩ) (2L ϩ Co2ϩ) Nickel 100 (3L ϩ Ni2ϩ) (2L ϩ Ni2ϩ) 100 (3L ϩ Ni2ϩ) (2L ϩ Ni2ϩ) Copper 100 (3L ϩ Cu2ϩ) (2L ϩ Cu2ϩ) 100 (3L ϩ Cu2ϩ) (2L ϩ Cu2ϩ)

nals for the 1,2-cyclohexanedione and 2,3-pentanedi- rotate away from each other to minimize pi orbital repul- one complexes may be weaker because the adjacent sions, therefore allowing only a single oxygen atom to positioning of the carbonyl groups prevents them interact strongly with the metal ion and permitting attach- from being strong chelators. Thus, many of the ment of additional ligands, albeit weakly bound. weakly bound ionic clusters may not survive the In the case of the quinones, the trends in formation of transport process through the ESI interface. complexes may also be rationalized by the two factors An interesting observation is the fact that no ionic mentioned above for the nonaromatic diketones: the complexes were seen for 1,4-cyclohexanedione with the occurrence of chelating interactions and the influence of alkali or any of the other classes of metals in this study. the electron-withdrawing effects of the carbonyl This preliminary result suggests two possible explana- groups. As indicated in Table 2, formation and detec- tions. First, the proximity of the carbonyl substituents tion of alkali metal complexes for 1,2-naphthoquinone may be crucial to the formation of stable metal com- or 9,10-phenanthrenequinone was commonplace. In plexes, meaning that chelating interactions are neces- contrast, for ESI of mixtures of the structural isomers, sary for stabilization of the complexes. Clearly chelating 1,4-naphthoquinone or anthraquinone, respectively, interactions are not possible for 1,4-cyclohexanedione. and alkali metals or the other metals in this study, no Moreover, the presence of two carbonyl groups at charged complexes were observed. Both 1,4-naphtho- opposite ends of the diketone ligand means that each quinone and anthraquinone possess carbonyl groups at one exerts a negative electron-withdrawing influence opposite sides of the ring, meaning that these ligands on the other, thus lowering their nucleophilicity, reduc- cannot chelate the metal and each carbonyl oxygen ing their coordination strength and weakening the has reduced coordination strength. A greater percent- carbonyl/metal interactions. Either of these two factors age of dimer complexes relative to monomer com- could prevent formation or survival of the 1,4-cyclohex- plexes was observed for 1,2-naphthoquinone and anedione/metal complexes. 9,10-phenanthrenequinone as the size of the alkali The formation of only dimers and trimers for 2,3- metal decreased. This trend is related to the greater pentanedione and the alkali metals contrasts to the charge density of the smaller alkali metals, yielding predominant formation of only monomer (1:1) com- stronger electrostatic bonds to the carbonyl oxygen plexes for the other diketones. It is speculated that for atoms in the dimers and promoting stabilization of the other diketones the metal is fully coordinated by the the dimer complexes. adjacent carbonyls, allowing the ligand to fold around the metal slightly, thus prohibiting the addition of other CAD of Alkali Metal/Diketone Complexes ligand attachment due to ligand–ligand repulsions. In the case of 2,3-pentanedione, the adjacent positions of Low-energy CAD of the alkali metal/diketone and the carbonyl groups may cause the carbonyl groups to alkali metal/quinone complexes under multiple colli- 406 ALADBOBL mScMs pcrm19,1,402–413 10, 1999, Spectrom Mass Soc Am J BRODBELT AND HALL Table 3. ESI and CAD results for Diketones with alkaline earth metalsa Mg Ca Sr Ba

% Ion CAD % Ion CAD % Ion CAD % Ion CAD

1,2-CHD 20 (2L ϩ Mg ϩ (2L ϩ Mg)2ϩ 100 (3L ϩ Ca)2ϩ (2L ϩ CaϪH)ϩ 100 (3L ϩ Sr)2ϩ (2L ϩ Sr Ϫ H)ϩ 20 (3L ϩ Ba)2ϩ (2L ϩ Ba)2ϩ MeOH)2ϩ (L ϩ H)ϩ (L ϩ H)ϩ (2L ϩ Sr)2ϩ 80 (L ϩ Mg Ϫ Hϩ (L ϩ Mg Ϫ H)ϩ 80 (2L ϩ Ba ϩ (2L ϩ Ba)2ϩ BB3 MeOH)ϩ MeOH)2ϩ (L ϩ Ba Ϫ H)ϩ (L ϩ H)ϩ 1,3-CHD 100 (4L ϩ Mg Ϫ H)ϩ (3L ϩ Mg Ϫ H)ϩ 40 (2L ϩ Ca ϩ (2L ϩ Ca ϩ 15 (2L ϩ Sr ϩ NPD 25 (2L ϩ Ba ϩ (2L ϩ Ba)2ϩ BB3 2MeOH)2ϩ MeOH)2ϩ MeOH)2ϩ MeOH)2ϩ (L ϩ Ba Ϫ H)ϩ (L ϩ H)ϩ 20 (3L ϩ Ca ϩ (3L ϩ Ca)2ϩ 25 (2L ϩ Sr ϩ (2L ϩ Sr ϩ 25 (3L ϩ Ba)2ϩ (2L ϩ Ba)2ϩ MeOH)2ϩ BB3 2MeOH)2ϩ MeOH)2ϩ (2L ϩ Ba Ϫ H)ϩ (2L ϩ Ca Ϫ H)ϩ (L ϩ H)ϩ (L ϩ H)ϩ 20 (4L ϩ Ca)2ϩ (3L ϩ Ca)2ϩ 25 (3L ϩ Sr)2ϩ (2L ϩ Sr Ϫ H)ϩ 15 (4L ϩ Ba)2ϩ (3L ϩ Ba)2ϩ (L ϩ H)ϩ 10 (5L ϩ Ca)2ϩ (4L ϩ Ca)2ϩ 20 (4L ϩ Sr)2ϩ (3L ϩ Sr)2ϩ 20 (4L ϩ Ba ϩ (4L ϩ Ba)2ϩ MeOH)2ϩ 10 (4L ϩ Ca Ϫ H)ϩ (3L ϩ Ca Ϫ H)ϩ 5 (5L ϩ Sr)2ϩ (4L ϩ Sr)2ϩ 10 (3L ϩ Ba Ϫ H)ϩ (2L ϩ Ba Ϫ H)ϩ

5 (3L ϩ Sr Ϫ H)ϩ (2L ϩ Sr Ϫ H)ϩ 5 (4L ϩ Ba Ϫ H)ϩ (3L ϩ Ba Ϫ H)ϩ 5 (4L ϩ Sr Ϫ H)ϩ (3L ϩ Sr Ϫ H)ϩ 1,4-CHD ND ND ND ND 2,3-PD ND ND ND ND 2,4-PD 5 (3L ϩ Mg)2ϩ (2L ϩ Mg)2ϩ 80 (3L ϩ Ca)2ϩ (2L ϩ Ca)2ϩ 50 (3L ϩ Sr)2ϩ (2L ϩ Sr)2ϩ 10 (4L ϩ Ba)2ϩ (3L ϩ Ba)2ϩ 5 (2L ϩ Mg Ϫ H)ϩ (L ϩ Mg Ϫ H)ϩ 20 (2L ϩ Ca Ϫ H)ϩ (L ϩ Ca Ϫ H)ϩ 50 (2L ϩ Sr ϩ (2L ϩ Sr)2ϩ 30 (3L ϩ Ba)2ϩ (2L ϩ Ba)2ϩ MeOH)2ϩ 90 (L ϩ M Ϫ H ϩ (L ϩ Mg Ϫ H ϩ 30 (2L ϩ Ba)2ϩ (L ϩ Ba Ϫ H)ϩ 2MeOH)ϩ MeOH)ϩ (L ϩ H)ϩ (L ϩ Ba)2ϩ 30 (2L ϩ Ba ϩ (2L ϩ Ba)2ϩ MeOH)2ϩ 2,5-HD Ͼ95 (3L ϩ Mg)2ϩ (2L ϩ Mg)2ϩ 90 (3L ϩ Ca)2ϩ (2L ϩ Ca)2ϩ 60 (3L ϩ Sr)2ϩ (2L ϩ Sr)2ϩ 40 (3L ϩ Ba)2ϩ (2L ϩ Ba)2ϩ BB3 (L ϩ Ca Ϫ H)ϩ ϩ (L ϩ H Ϫ H2O) Ͻ5 (4L ϩ Mg)2ϩ (3L ϩ Mg)2ϩ 10 (4L ϩ Ca)2ϩ (3L ϩ Ca)2ϩ 40 (4L ϩ Sr)2ϩ (3L ϩ Sr)2ϩ 60 (4L2ϩ Ba)2ϩ (3L ϩ Ba)2ϩ aNPD ϭ no CAD products detected. ND ϭ no adducts detected. BB3 ϭ broadband CAD applied to dissociate the initial CAD product. CHD ϭ cyclohexanedione. PD ϭ pentanedione. HD ϭ hexanedione. J Am Soc Mass Spectrom 1999, 10, 402–413 DIKETONE/METAL ION COMPLEXES 407

stems from the greater charge density of the doubly charged alkaline earth metals, a factor that promotes stronger binding interactions. No complexation was observed for 1,4-cyclohexanedione or 2,3-pentanedione, whereas the cyclic analog of the former, 1,2-cyclohexandione, and the 2,4-isomer of the latter, 2,4-pentanedione, form intense complexes. The inefficient metal complexation by 2,3-pentanedione and 1,4-cyclohexanedione is believed to be related to their poor chelating properties, meaning that both of the dipoles associated with the oxygen atoms cannot align optimally for binding the metal ion, as discussed above in the alkali metal complexation section. Overall the intensity of the alkali metal complexes were much greater than complexes with dou- Figure 2. ESI mass spectrum of 2,5-hexanedione with calcium bly charged alkaline earth metals, likely because of the chloride. The predominant signal corresponds to (3L ϩ Ca2ϩ). A ϩ greater efficiency of desolvation of the singly charged second complex ion is identified as (4L ϩ Ca2 ). alkali metal complexes relative to desolvation of the doubly charged alkaline earth complexes in the ESI inter- sion conditions typically results in loss of entire ligands face. (Table 1), indicating an orderly cleavage of the electro- In contrast to the predominant complexation pattern ϩ static bonds between the metal and the ligands. An via formation of the trimers [i.e., (3L ϩ M2 )] for 1,2- interesting deviation from this trend was discovered for cyclohexanedione and 2,5-hexanedione is the behavior the complexes with 2,3-pentanedione. CAD of the po- of 1,3-cyclohexanedione in which higher order com- tassium, rubidium, and cesium dimer and trimer complexes (i.e., doubly charged tetramers and pentamers) plexes resulted in loss of all of the ligand units, yielding were observed along with the detection of singly only the bare metal ion, indicating that the ligands were charged trimer and tetramer complexes. The formation weakly bound. However, for the complex with sodium, of singly charged alkaline earth metal complexes of the ϩ ϩ CAD of the trimer yielded loss of just one ligand to type (nL Ϫ H ϩ M2 )(n ϭ 2 to 4) for 1,3-cyclohex- form a stable dimer. Sodium is smaller and thus more anedione and 2,4-pentanedione was the first evidence densely charged, therefore each ligand is more tightly of charge reduction processes in this study. For 2,4- bound and the dimer is stabilized. In several CAD pentanedione, the charge reduction was observed only experiments involving a variety of sodium complexes, for the magnesium and calcium complexes (with the the precursor ion disappeared, but no product ions exception of the CAD of the barium dimer complex as were detected presumably because of the inability to discussed below), whereas for 1,3-cyclohexanedione monitor the m/z value for the sodium ion under the this charge reduction was observed upon ESI of all of conditions used to trap the precursor complex. Estima- the alkaline earth metal solutions. The formation of the tion of bond energies based on the CAD results was not singly charged complexes is presumed to occur through attempted because of the inability to accurately model displacement of a proton in the enol form of the the energy deposition of the CAD process and the lack diketone upon coordination of the metal ion which is of information about the initial internal energy of the first bound to one or more diketone ligands as illus- diketone/metal complexes. trated in Scheme 1. The deprotonation step to produce the charge-reduced complexes involves proton transfer Formation of Alkaline Earth Metal/Diketone to another diketone or solvent molecule (not shown in Complexes the Scheme for simplification), followed by elimination of the protonated product. The complexation of alkaline earth metal ions is a more This process may reflect a solution reaction and/or interesting situation because the metal ions are doubly electrospray phenomenon. If this reaction sequence is charged and may promote stronger interactions than correct, it would seem reasonable to expect fewer or no the singly charged alkali metal ions. The predominant singly charged alkaline earth complexes for 1,2-cyclo- complexation pattern observed for the mixtures of hexanedione and 2,5-hexanedione which do not favor diketones and alkaline earth metals is the formation of enolization in methanol [28–31]. In addition, the acidity doubly charged trimer complexes readily seen by the of the enol proton in 1,2-cyclohexanedione is much electrospray process (Table 3), along with formation of lower than the acidity of the enol proton in 1,3-cyclo- some tetramer, pentamer, and charge reduced com- hexanedione [32, 33], thus disfavoring the loss of the plexes. An example of a typical ESI mass spectrum is proton from 1,2-cyclohexanedione. In fact, only doubly shown in Figure 2 for 2,5-hexanedione with calcium. charged species were observed for 2,5-hexanedione and The domination of trimer and higher order complexes 1,2-cyclohexanedione, and the charge reduced com- for the alkaline earth metals relative to formation of plexes were absent. Another plausible explanation for mostly monomers and dimers for the alkali metals formation of the charge reduced complexes is that 408 HALL AND BRODBELT J Am Soc Mass Spectrom 1999, 10, 402–413

Scheme 1. Proposed pathway for formation of charge reduced complexes.

ϩ 2ϩ ϩ spontaneous dissociation of a doubly charged complex signed as (nL M CH3OH) are also observed, espe- ϩ occurs during the electrospray process or from colli- cially for 1,2-cyclohexanedione with Ba2 , 1,3-cyclohex- ϩ ϩ ϩ sions in the ion trap mass spectrometer. This alternative anedione with Ca2 ,Sr2 , and Ba2 , and 2,4-pentanedione ϩ process is supported by several CAD studies as dis- with Sr2 (Table 3). The formation of these methanol- cussed below for dissociation of the 1,2-cyclohexanedi- containing complexes indicates that methanol is able to one/alkaline earth metal complexes. compete effectively for occupation of one coordination site The formation of doubly charged tetramer and pen- of the metal ion, a factor which is likely enhanced in tamer complexes for 1,3-cyclohexanedione may be con- certain cases by the small size of methanol and a lower trasted to the behavior of its linear analog, 2,4-pen- degree of ligand–ligand repulsions relative to that of the tanedione, in which trimers were the highest order bulkier diketones. In addition, the percentage of methanol complexes observed with magnesium, calcium, and is much greater relative to that of the diketone in the strontium. This difference in the number of diketone original mixture, giving it a statistical preference for inclu- ligands coordinated to the metal ion may be rational- sion into some of the surviving complexes. The fact that ized by recognizing that the chelation interactions of the methanol-containing complexes are only observed for 2,4-pentanedione are more optimized than those of specific combinations of diketones and alkaline earth 1,3-cyclohexanedione, which has a degree of ring strain metals suggests that the space requirements of the chelat- upon chelation. Thus, 2,4-pentanedione can more effec- ing interactions and the size of the metal both play integral tively chelate the metal ion, and three ligands fully roles. CAD of these complexes yielded loss of methanol to ϩ coordinate one metal ion. Each 1,3-cyclohexanedione give (nL ϩ M2 ), indicating that the methanol molecule is engages in weak chelating interactions or only a single the most weakly bound ligand coordinated to the metal binding interaction meaning that more molecules can ion. surround the metal ion for complete coordination, resulting in stable tetramer and pentamer complexes. CAD of Alkaline Earth/Diketone Complexes The behavior of the two quinones, 1,2-naphthoquinone and 9,10-phenanthrenequinone, with the alkaline Generally, CAD of the doubly charged alkaline earth earth metals was more straightforward with only dou- complexes (Table 3) predominantly yields loss of one bly charged trimer, tetramer, and pentamer complexes entire diketone with the complex retaining its initial ϩ2 observed (Table 2). A general trend was noticed in charge, indicating that these complexes disassemble by which the larger alkaline earth metals could accommo- an orderly loss of diketone molecules. CAD of the date a greater number of ligands, attributed to lessening quinone complexes (Table 2) likewise simply results in of steric interactions between ligands as the size of the the loss of an entire ligand with the products retaining metal increases. Charge reduced complexes are not their ϩ2 charge. A notable exception to this trend is the observed upon ESI of either of these quinones with the CAD behavior of the series of doubly charged trimer alkaline earth metals. This absence of charge reduction complexes of 1,2-cyclohexanedione with calcium, stron- is explained by the unavailability of an acidic proton tium, and barium. The barium-containing trimers favor which must transfer to a neighboring ligand as with the the loss of an entire molecule of 1,2-cyclohexanedione, diketones discussed above (see Scheme 1), and appar- whereas the analogous calcium and strontium com- ently correlates with their keto/enol distribution. As plexes dissociate via the loss of protonated 1,2-cyclo- ϩ ϩ mentioned previously, the other two analogs, 1,4-naph- hexanedione to form singly charged (2L Ϫ H ϩ M2 ) thoquinone and anthraquinone, do not form any type of ions. Figure 3 illustrates this phenomenon for the bari- alkaline earth metal complexes. This failure may stem um- and calcium-containing trimers. In Figure 3A, the ϩ from the inability of both oxygen atoms to simulta- (3L ϩ Ba2 ) complex dissociates exclusively by loss of neously interact with a metal ion, and the electron- one entire 1,2-cyclohexanedione molecule. In contrast ϩ withdrawing property that each carbonyl group exerts as shown in Figure 3B, the (3L ϩ Ca2 ) complex disso- on the other, reducing their nucleophilicity. ciates to form protonated 1,2-cyclohexanedione and ϩ ϩ Upon spraying some of the diketone/alkaline earth (2L Ϫ H ϩ Ca2 ), both singly charged product ions metal solutions, unusual doubly charged complexes as- that stem from an intramolecular proton transfer be- J Am Soc Mass Spectrom 1999, 10, 402–413 DIKETONE/METAL ION COMPLEXES 409

cule. There is no evidence to confirm how many of the 1,2-cyclohexanedione molecules are in the enol versus keto forms, so other variations of Scheme 2 could be operative. This gas-phase collisionally activated charge reduction process provides a striking parallel to the well-known reactions of diketones in solution. ϩ For the Ca2 complexes involving 1,3-cyclohexanedione, application of a broadband activation waveform results in further dissociation of the primary fragments listed in Table 3. For example, [4(1,3-cyclohexanedi- ϩ one) ϩ Ca2 ] was subjected to extended broadband activation, resulting in decomposition of the fragment ϩ ions labeled (3L ϩ Ca2 ) (listed in Table 3). These ions undergo secondary dissociation to yield fragment ions ϩ assigned as (L ϩ H) that match the ones obtained upon CAD of protonated 1,3-cyclohexanedione. Proton- ated 1,3-cyclohexanedione (m/z 113) dissociates pre-

dominantly by loss of water or C2H2O, along with formation of minor fragment ions at m/z 55, 61, and 67. The similarities in the fragmentation patterns offer further confirmation that the process shown in Scheme 2 (i.e., intramolecular proton transfer with elimination of a molecule of protonated diketone) is a reasonable one. Interestingly, for the [3(1,2-cyclohexanedione) ϩ ϩ ϩ ϩ Sr2 ] complexes but not for the analogous Ba2 or Ca2 trimers, both types of pathways are observed (i.e., proton transfer to form the charge reduced products ϩ Figure 3. (A) SWIFT isolation and CAD of (3L ϩ Ba)2 where and loss of neutral ligands leading to doubly charged L ϭ 1,2-cyclohexanedione. Loss of one unit of 1,2-cyclohexanedi- ϩ products). These findings are presumed to be related to one to yield (2L ϩ Ba)2 is the predominant fragmentation pathway. (B) SWIFT isolation and CAD of (3L ϩ Ca)2ϩ where L ϭ the size of the metal ion and its charge density. Barium 1,2-cyclohexanedione. The trimer predominantly fragments to is the biggest and least charge dense, thus the three ϩ yield two monopositive ions, one corresponding to (L ϩ H) and 1,2-cyclohexanedione units are more weakly bound. In ϩ 2ϩ Ϫ ϩ the second the complementary ion (2L Ca H ). addition, the three cyclohexanedione units should be spaced further apart from each other because barium is tween two 1,2-cyclohexanedione molecules attached to larger, thus making it harder to accommodate the ϩ Ca2 . This general process is illustrated in Scheme 2,in proximity requirement for the critical proton transfer which one diketone molecule becomes a diketonate and between two cyclohexanedione ligands. As the size of another diketone is eliminated as a protonated mole- the metal ion shrinks, the cyclohexanedione ligands are positioned more closely and are held more tightly. Therefore, proton transfer is facilitated, and the favored ϩ ϩ product is (2L Ϫ H ϩ M2 ). If CAD is performed on ϩ the [2(1,2-cyclohexanedione) ϩ Ba2 ] complex, the proton transfer reaction is observed. When fewer ligands ϩ are bound to Ba2 , the metal–ligand bonds are stronger and shorter, bringing the ligands closer together and facilitating the possibility of the intraligand proton- transfer reaction. Of all the other doubly charged diketone/alkaline earth metal complexes, only a few specific complexes undergo the same type of proton transfer/ charge reduction process described for the 1,2- ϩ cyclohexandione trimers. The 1,3-cyclohexanedione/Sr2 ϩ and 1,3-cyclohexanedione/Ba2 trimers, and the 2,4-pen- ϩ tanedione/Ba2 dimers follow this same dissociation route. Apparently the size of the metal and the spacing of ϩ 2ϩ Scheme 2. Proposed fragmentation pathway for (3L Ca) the two carbonyl groups greatly influence this process. where L ϭ 1,2-cyclohexanedione. The doubly charged complex dissociates via loss of protonated 1,2-cyclohexanedione to form The acidity of the enol hydrogen may also play a role, but the charge reduced complex (2L ϩ Ca2ϩ Ϫ Hϩ). the gas-phase acidities are unknown. 410 ALADBOBL mScMs pcrm19,1,402–413 10, 1999, Spectrom Mass Soc Am J BRODBELT AND HALL

Table 4. ESI and CAD results for diketones with transition metalsa Co Ni Cu

Compound % Ion CAD % Ion CAD % Ion CAD

1,2-Cyclohexanedione 100 (2L ϩ Co Ϫ H)ϩ Ϫ14 100 (2L ϩ Ni Ϫ H)ϩ Ϫ30 100 (2L ϩ Cu Ϫ H)ϩ NPD Ϫ28 Ϫ56 Ϫ80 Ϫ94 Ϫ94 (L ϩ Co Ϫ H)ϩ 1,3-Cyclohexanedione 30 (3L ϩ Co Ϫ H)ϩ (2L ϩ Co Ϫ H)ϩ 100 (3L ϩ Ni Ϫ H)ϩ (2L ϩ Ni Ϫ H)ϩ 100 (2L ϩ Cu Ϫ H)ϩ Ϫ80 Ϫ94 (L ϩ Cu Ϫ H)ϩ 70 (4L ϩ Co Ϫ H)ϩ (3L ϩ Co Ϫ H)ϩ 1,4-Cyclohexanedione ND ND ND 2,3-Pentanedione ND ND ND 2,4-Pentanedione 50 (L ϩ Co Ϫ H ϩ (L ϩ Co Ϫ H ϩ 50 (L ϩ Ni Ϫ H ϩ (L ϩ Co Ϫ H ϩ 40 (L ϩ Cu Ϫ H ϩ Ϫ14 2MeOH)ϩ MeOH)ϩ 2MeOH)ϩ MeOH)ϩ MeOH)ϩ (L ϩ Cu Ϫ H)ϩ 45 (2L ϩ Co Ϫ H)ϩ Ϫ42 45 (2L ϩ Ni Ϫ H)ϩ Ϫ42 40 (L ϩ Co Ϫ H ϩ (L ϩ Cu Ϫ H ϩ Ϫ68 Ϫ68 2MeOH)ϩ MeOH)ϩ Ϫ82 Ϫ82 5 (3L ϩ Co)2ϩ (2L ϩ Co Ϫ H)ϩ 5 (3L ϩ Ni)2ϩ (2L ϩ Ni Ϫ H)ϩ 20 (2L ϩ Cu Ϫ H)ϩ Ϫ42 (L ϩ H)ϩ (L ϩ H)ϩ Ϫ68 Ϫ82 2,5-Hexanedione 25 (2L ϩ Co)2ϩ Ϫ46 10 (2L ϩ Ni ϩ MeOH)2ϩ (2L ϩ Ni)2ϩ 15 (2L ϩ C)2ϩ Ϫ75 (L ϩ Co Ϫ H)ϩ BB3 (L)ϩ ϩ ϩ ϩ (L ϩ Co Ϫ H ϩ H ϩH2O) (L ϩ Co Ϫ H) (L ϩ Cu) (L ϩ Co Ϫ H ϩ (L ϩ H)ϩ ϩ ϩ MeOH) (L ϩ H Ϫ H2O) 75 (3L ϩ Co)2ϩ (2L ϩ Co)2ϩ 90 (3L ϩ Ni)2ϩ (2L ϩ Ni)2ϩ 85 (3L ϩ Cu)2ϩ (2L ϩ Cu)2ϩ (2L ϩ Co Ϫ H)ϩ (2L ϩ Ni Ϫ H)ϩ (2L ϩ Cu Ϫ H)ϩ (L ϩ H)ϩ (L ϩ H)ϩ (L ϩ H)ϩ aNPD ϭ no CAD product detected. ND ϭ no adducts detected. BB3 ϭ broadband CAD applied to dissociate the initial CAD product. J Am Soc Mass Spectrom 1999, 10, 402–413 DIKETONE/METAL ION COMPLEXES 411

Table 5. Keto/enol distribution in methanol Neither 1,4-cyclohexanedione nor 2,3-pentanedione Compound Percent enol form transition metal complexes, as was noted for the alkali and alkaline earth metal experiments. The linear 1,2-Cyclohexanedione 40 diketone 2,4-pentanedione forms both singly charged 1,3-Cyclohexanedione 95 1,4-Cyclohexanedione 1 complexes with all of the transition metals as well as 2,3-Pentanedione Ͻ0.1 minor amounts of doubly charged complexes with 2,4-Pentanedione 70 cobalt and nickel. As with the alkaline earth metals, 2,5-Hexanedione Ͻ0.5 2,5-hexanedione only forms the doubly charged complexes reflects the inability of 2,5-hexanedione to form a stable enol form which is favored for 1,3-diketones. Formation of Transition Metal/Diketone Complexes However, because 2,5-hexanedione can still function as a strong chelator, it does successfully form stable metal Complexation of the transition metal ions is the most complexes, unlike the other two diketones, 1,4-cyclo- interesting case because these metal ions are doubly hexanedione and 2,3-pentanedione. charged and show specific binding geometries [34]. The A trend influenced by the size and electronic nature ESI and CAD results for the diketones and quinones of the metal ion emerges when comparing the compl- with transition metals are summarized in Tables 4 and exation behavior of the transition vs. alkaline earth 2, respectively. In contrast to alkaline earth metal com- metals. For example, 2,5-hexanedione forms only dimer plexation, the formation of singly charged complexes is and trimer doubly charged complexes with the transi- dominant for the transition metals with 1,2-cyclohex- tion metals, whereas for the alkaline earth metals higher anedione, 1,3-cyclohexanedione, and 2,4-pentanedione. order tetramer complexes are observed. Furthermore, The type of transition metal complex formed was found both tetramer and pentamer complexes of 1,3-cyclohex- to generally reflect the keto-enol equilibrium behavior anedione with all of the alkaline earth metals except in solution and the acidity of the enol proton. Diketones magnesium were detected, but only dimers, trimers and with higher percentages of enol form and those with some tetramers are observed upon complexation with more acidic enol protons are typically associated with the transition metals. The general ability of the alkaline formation of singly charged complexes. Table 5 lists the earth metals to accommodate a greater number of percentage of the enol form in solution based on previ- ligands is attributed to their nonspecific binding geom- ous studies of keto-enol equilibrium for the diketones etries and larger ionic radii which may range from 0.99 reported in the literature [28–31]. For two of the cyclic to 1.35 Å from calcium to barium [34]. In contrast, the diketones, 1,2- and 1,3-cyclohexanedione, only singly transition metal have specific binding geometries and charged complexes were detected which is in contrast the ionic radii for cobalt, nickel, and copper range from to the predominant formation of doubly charged com- 0.72 to 0.89 Å for the most stable coordination numbers plexes observed for these two ligands with the alkaline and geometries [34]. The ionic radii of the metal ions earth metals. This result indicates that the electronic may impact the degree of ligand–ligand repulsions in nature of the metal, in addition to the keto-enol distri- the multiligated complexes. Thus, the complexation bution of the diketone, also plays a pivotal role in the trends observed in the ESI mass spectra can be corre- production of singly charged complexes upon ESI. The lated with the sizes and electronic natures of the metal formation of singly charged complexes of the diketones ions, two factors that affect the favored coordination with the transition metals is presumed to occur via the geometries and severity of ligand–ligand repulsions. same processes as discussed with the alkaline earth Although we have indicated the formation of charge metals (i.e., displacement of the enol proton in solution reduced complexes, there is no evidence for a formal or via spontaneous fragmentation in the ESI interface or change in the oxidation states of the metal ions. Thus, in the mass spectrometer). The preferential formation of we view the complexes as involving metal ions in their charge-reduced transition metal complexes is related to ϩ2 oxidation states surrounded by one or more neutral the availability of d orbitals of the metal which promote diketone ligands and one negatively charged diketonate formation of the oxygen–metal dative bonds. The 5% ligand, thus giving the complex a net ϩ1 charge. In light ϩ ϩ formation of (3L ϩ Co2 ) and (3L ϩ Ni2 ) but 0% of this view, the role of the ionization potential of the ϩ formation of (3L ϩ Cu2 ) complexes for 2,4-pentanedi- diketone ligand does not play a significant role in one in Table 4 falls within the range of reproducibility influencing the favorability of the charge reduction of the ESI measurements and thus is not interpreted as process [15, 16]. ϩ ϩ ϩ a striking change in the ability of Co2 ,Ni2 , and Cu2 The complexation of the quinones with the transition ions to promote the charge-reduction processes. The metals follow similar guidelines. The detection of only signals for complexes with 1,3-cyclohexanedione were trimer complexes of 1,2-naphthoquinone and 9,10- more intense than with 1,2-cyclohexanedione and fol- phenanthrenequinone with the transition metals (Table lowed a general trend from cobalt to copper of binding 2), in contrast to higher order complexes with the fewer ligands to the metal. This trend is in agreement alkaline earth metals, is likewise indicative of the ϩ with the preferred square planar geometry of Cu2 vs. tighter bonding constraints in terms of the geometry ϩ ϩ octahedral geometry of Co2 and Ni2 [34]. preferences typically exhibited by the transition metals. 412 HALL AND BRODBELT J Am Soc Mass Spectrom 1999, 10, 402–413

The intense trimer complexes observed for the quinones and transition metals reflect the favorable chelation properties of the quinones, thus limiting the number of ligands that coordinate to metal ions that have specific binding geometries. The absence of charge reduced complexes is attributed to the inability of the ␣-quinones to form stable enol structures, thus preventing interligand proton transfer.

CAD of Transition Metal/Diketone Complexes CAD studies of the transition metal complexes revealed several interesting trends (see Table 4). In general there Figure 4. SWIFT isolation and CAD of [2(2,5-hexanedione) ϩ Ni2ϩ ϩ MeOH] with SWIFT waveform extended to dissociate was found to be more fragmentation pathways that ϩ [2(2,5-hexanedione) ϩ Ni2 ] with the resulting fragments pointed involved cleavage of covalent bonds of the ligand in out with arrows. The ion at m/z 96 is assigned as spontaneous contrast or in addition to simple removal of ligands or loss of water from (2,5-hexanedione ϩ H)ϩ. Note that the charges charge reduction processes as noted previously for the for ions containing nickel are easily determined by examination of alkaline earth complexes. This ligand fragmentation the mass separation of the nickel isotopes. ϩ ϩ was especially noted for (2L Ϫ H ϩ M2 ) where L ϭ 1,2-cyclohexanedione and 2,4-pentanedione, and M ϭ ation to yield fragment ions that match the ones obtained Co, Ni, or Cu. For example, the [2(1,2-cyclohexanedi- ϩ ϩ upon CAD of protonated 2,5-hexanedione. Protonated one) Ϫ H Co2 ] complex dissociated by loss of 28, 80, 2,5-hexanedione (m/z 115) dissociates by loss of one or of 94 amu, all processes which must involve fragmen- two molecules of water or loss of 42 or 46 u. Because the tation of 1,2-cyclohexanedione. Such pathways suggest fragmentation patterns match, it offers support that the that the ligands are strongly bound to the metal, and type of process shown in Scheme 2 (i.e., intramolecular thus covalent bond cleavages within the diketone li- proton transfer with elimination of a molecule of proton- gands are favored over elimination of an entire ligand ated diketone) may adequately explain the structures of via cleavage of the strong dative bonds between the charge-reduced complexes that are formed upon dissoci- carbonyl oxygen atoms and the metal ion. ation of the transition metal complexes. Charge reduction upon CAD of all the doubly CAD of the dimer complex of 2,5-hexanedione with charged linear diketone complexes (see Scheme 2), such ϩ copper resulted in the first appearance of odd-electron as noted for [3(2,4-pentanedione) ϩ Co2 ], for [3(2,4- ϩ fragments observed in this study (Figure 5). It is be- pentanedione) ϩ Ni2 ], and for [3(2,4-hexanedione) ϩ ϩ lieved that an intramolecular charge transfer process M2 ], was uniformly observed which contrasts with the occurs in which the copper (II) is reduced to copper (I), results of the analogous doubly charged alkaline earth as opposed to the discussions above which reflect a complexes which underwent charge reduction and/or reduction of the overall charge of the complex through loss of entire diketone molecules. This uniform prefer- proton transfer while maintaining the formal ϩ2 oxida- ence for charge reduction again reflects the ability of the tion state of the metal. Several previous studies have transition metals to form strong dative bonds with the noted a similar intramolecular charge transfer process deprotonated ligand (i.e., diketonate). CAD of the transition metal complexes containing 2,5-hexanedione provides another interesting contrast to the CAD behavior of the analogous alkaline earth metal complexes. The doubly charged alkaline earth complexes disassemble by loss of 2,5-hexanedione molecules, producing doubly charged complexes. The CAD ϩ spectrum for [2(2,5-hexanedione) ϩ Ni2 ] is shown in Figure 4. Despite the fact that 2,5-hexanedione does not favor the enol form nor does it have a highly acidic proton, apparently complexation to a transition metal ion promotes the interligand proton transfer described in Scheme 2, and a protonated ligand is eliminated. Application of a broadband activation waveform for ϩ the Co2 complexes involving 2,5-hexanedione results in further dissociation of the primary fragments listed ϩ ϩ in Table 4. For example, [3(2,5-hexanedione) ϩ Co2 ] Figure 5. SWIFT isolation and CAD of [2(2,5-hexanedione) Cu2ϩ]. 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