The Stabilizing Role of Cyclodextrins on Keggin Phosphotungstic Acid by Complexation Unveiled by Electrospray Mass Spectrometry

: This study demonstrated the stabilizing role of a cyclodextrin on Keggin [PW 12 O 40 ] 3- via hydrogen bonding complexation unveiled by ESI-MS. The distinctive fragmentation pathways of the {PW 12 }/ γ -CD complexes from that of discrete [PW 12 O 40 ] 3- showed that the so-called “weak” non-covalent interactions can effectively change the dissociation chemistry of POM in the gas phase. The influence of different types of solvents and organic additives such as γ -CD on the stability of Keggin [PW 12 O 40 ] 3- was also addressed firstly by ESI-MS.


Introduction
Polyoxometalates (POMs), anionic early transition metal oxide clusters, are attractive inorganic building blocks owing to their distinctive structures and excellent catalytic properties, which lead to a vast range of applications. 1,2 One of the fundamental aspects that bother POM chemists is their limited stability in aqueous solutions (at nearly neutral or basic pH) which tremendously narrows the scope of their application as catalysts 3 or antiviral and antitumoral drugs 4 in the chemical or biological systems. Although organic solvents can effectively protect POM skeleton from degradation and aggregation, 5 they are strictly used in the synthetic biomimetic systems. 6 Therefore finding an alternative to replace organic solvents is rather demanding for both synthetics and application purposes.
Cyclodextrins (CDs), torus-like macro-rings built up from glucopyranose units and known to form non-covalent complexes with many organic compounds, 7 10-in the absence of β-CD) due to the formation of water-soluble complexes with β-CD (β-). Wang et al. 15 used vanadium-substituted heteropoly acids/cyclodextrin complexes (PMoV n -β-CD, n = 1, 2) as phase transfer catalysts in direct hydroxylation of benzene to phenol. However, in-depth investigation on the structural feature of POM/CD complexes is lacking.
In this study, we employed ESI-MS to present how cyclodextrin can dramatically improve the stability of Keggin phosphotungstic acid (formulated as H 3 PW 12 O 40 ) in both aqueous phase and gas phase via complexation with g-CD. In addition, the influence of different types of solvents on the stability of Keggin H 3 PW 12 O 40 was also addressed firstly by ESI-MS.

Experimental
Sample preparation. All reagents were purchased from commercial sources and used without further purification. Solutions were prepared at concentrations of approximately 10 -5 M using ultra-purified solvent.
Mass spectrometry. Mass spectrometric experiments were performed using an Agilent 6520 Q-TOF LC/MS mass spectrometer in the negative ion mode. The dualspray electrospray ionization source condition was as follows: Vcap 3500 V; skimmer 65 V; drying and nebulizer CD 1 ⊃ *Reprint requests to Jie Cao and WenJie Wu E-mail: jcao@bit.edu.cn; wwjie@tust.edu.cn.
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gas N 2 ; nebulizer 30 psi; drying gas flow 9 L/min; drying gas temperature 330 o C; fragmentor 100 V; scan range 50-3000 m/z; injection volume 0.5 mL. The samples were transferred to the electrospray source via an autosampler with a flow rate of 0.2 mL/min. CID experiments were performed using N 2 as the target gas. Each experiment was repeated at least three times under the same experimental conditions.

Results and discussion
How solvents and γ-CD affect the solution stability of   /z 249, 75%). This is a very important experimental evidence which implies that the composition of POM catalyst may change during the reaction course when the reaction media is pure water.
However, the poor stability of H 3 PW 12 O 40 can be greatly improved by using pure organic solvents or even mixed organic/water solvents. Figs. 1(b)-1(e) show the existence of intact polyoxoanion of [PW 12 O 40 ] 3at m/z 958 and [HPW 12 O 40 ] 2at m/z 1438. Note that even a small proportion of organic solvent in an aqueous solution could prevent H 3 PW 12 O 40 from dissociation. This strategy is also applicable for other POMs. 5 Is it possible to find an alternative in lieu of organic solvents to some extent in order to stabilize the fragile POM's skeleton in pure H 2 O? Fig. 1(f)  The instrument parameters in particular the fragmentor voltage, which is the difference between the capillary and skimmer potentials in the source-analyzer interface region of the mass spectrometer, play a key role on the detection of POM-based non-covalent complexes in the gas phase. Increasing the fragmentor voltage from 120 to 180 V led to a dissociation of the {PW 12 }/γ-CD complexes into lownuclearity species (e.g. W 4 and W 5 ). The fragmentor voltages were chosen to maximize gas-phase yields and minimize decompositions of the target analyte.
The gas-phase fragmentations of non-covalent {PW 12 }/γ-CD complexes As defined in Ma's work 16 as well as our previous paper 17 that a common fragmentation feature for the bare polyoxoanion [PW 12 O 40 ] 3is to yield pairs of complementary showed that the so-called "weak" non-covalent interactions can effectively change the dissociation chemistry of POM in the gas phase. Also, the influence of different types of solvents on the solution stability of H 3 PW 12 O 40 was presented by ESI-MS. The poor stability of H 3 PW 12 O 40 in pure H 2 O can be greatly improved either by dissolving it in pure organic or mixed organic/water solvent or by addition of γ-CD in pure H 2 O. The latter strategy provides a valuable alternative in addition to organic solvents to keep the polyoxoanion intact in solution. Moreover, the synergy with respect to structure and catalytic property will bring the POM/CD complexes into more fascinating applications particularly as (inorganic-organic) hybrid catalysts. Further study on the enhanced catalytic activity of {PW 12 }/γ-CD is in progress.