Mass Spectrometric Characterization of Dendrimers
Dendrimers are onion-type polymers with branching units in each shell - such as the POlyaminoPropylene AMine (POPAM) dendrimer exemplarily shown in the figure. The number of branches increases exponentially from the core outwards. Synthetically, repetitive reactions steps can be used to build up such a structure in either a divergent strategy from the core outwards or in a convergent approach starting with the periphery and working towards the core. For the dendrimer chemist, the issue of purity and the presence of defects are not always trivial-to-solve analytical questions. Since NMR experiments are sometimes of quite limited use, mass spectrometry has played a significant role in dendrimer chemistry, because all defects have masses deviating from those of the structure-perfect dendrimer.
A mass spectrometer can also be used as a laboratory to study isolated dendrimer molecules in the gas phase or their host–guest complexes. Since the properties of molecules under environment-free conditions are often quite different from those in solution, their gas-phase chemistry provides valuable new insight into properties, which cannot easily be studied in solution.
The studies on mass spectrometry of dendrimers in the Schalley group can be summarized as follows:
- Characterizing dendrimers and analyzing ionization artifacts
- Differentiation between several, sometimes even isomeric defects through tandem MS experiments
- Gas-phase studies on self-assembling metallo-supramolecular dendrimers
- Gas-phase chemistry of dendritic host-guest complexes: The analysis of dendritic effect occurring in the fragmentation of dendritic host–guest complexes
1. Characterizing Functionalized Fréchet and POPAM Dendrimers and Analyzing Ionization Artifacts
The soft ionization techniques ESI (ElectroSpray Ionization) and MALDI (Matrix-Assisted Laser Desorption-Ionization), which help the ionization of dendrimers as intact species, give insight into defect structures. On one hand, however, there might be ionzation artifacts as observed in the ESI spectra of POPAM dendrimers. On the other hand, defects may be generated during the ionization as shown below for the MALDI experiments done with persulfonylated POPAM dendrimers. It is therefore useful to combine both ionization methods in order to prevent false results. In MALDI-MS experiments, the choice of matrix can play an important role and thus it is advisable to test different matrices.
(a) MALDI mass spectrum (matrix: 2,5-dihydroxy-benzoic acid, DHB) of the second generation POPAM dendrimer shown in the inset. (b) ESI-FTICR mass spectrum of a ca. 50mM solution of G2 POPAM dendrimers in methanol with 1% acetic acid. (c) ESI-FTICR mass spectrum of G2 POPAM dendrimers obtained under the same conditions, but with a dendrimer sample which was stirred in water before ionization. While the MALDI mass spectrum indicates a pure dendrimer, electrospray ionization generates imine artifacts, which upon addition of water can be efficiently suppressed.
Top: ESI mass spectrum of a 50 mM methanol solution (1% acetic acid) of the persulfonylated dendrimer shown in the inset. Bottom: MALDI mass spectrum (matrix: DHB) of the same dendrimer. Note that the loss of 907 amu corresponds to a fragmentation reaction in the gas phase as evidenced by tandem MS experiments with the ESI-generated, mass selected parent ion. While ESI-MS experiments indicate a structure-perfect dendrimer, the MALDI mass spectrum is crowded with seemingly defect dendrimers. However, these defects are generated during ionization.
2. Differentiation of several, sometimes even Isomeric Defects through Tandem MS Experiments
In an attempt to synthesize pertosylated G1 POPAM dendrimers, a complex mixture of different structures is obtained including the structures shown below. Some of the defects are isomeric, i.e. they have the same elemental composition and thus the same exact mass. The structure of defect dendrimers can be analyzed with a CID (collision induced dissociation) experiment in the cell of an FTICR spectrometer. From the fragments of the mass-selected ion, a clear assignment of the structures is possible.
The analysis of the CID mass spectra of the structure-perfect analogue leads to the following mechanism of fragmentation:
3. Gas-Phase Studies on Self-Assembling Metallo-Supramolecular Dendrimers
Self-assembly under thermodynamic control is an efficient way to synthesize more complex structures from simple but suitably programmed building blocks. Self-assembled systems require reversibility for error correction and contain non-covalent bonds. For their characterization, and analysis of the solution host-guest chemistry, mass spectrometry with soft ionization techniques is ideal.
Shown above is an example of such a metallosupramolecular square with dendritic ligands, of which the NMR spectra suffer from the superposition of large numbers of sets of signals arising from slow dynamic processes. From the principally possible unlimited possibilities of structures ranging from open chains to triangles, squares, hexagons etc. ESI-MS confirms that exclusively squares are formed.
ESI-FTICR mass spectra of second generation squares with (dppp)Pd(II) (top) and (dppp)Pt(II) (bottom) corners and dendron-substituted 4,4'-bipyridines. These self-assembled dendritic squares bear a total of eight Fréchet dendrons.
4. Gas-phase Chemistry of Dendritic Host-Guest Complexes
From solution studies, it was known that the Klärner tweezers shown below (inset) with their extended aromatic surfaces binds electron-deficient viologen dications. This is also true for the dendron-decorated viologens. Due to the charge repulsion, the smaller generation uncomplexed viologens can not be obtained as their dications in the gas phase. For higher generations, dendron arms stabilizes the dication.
When the tweezers are added, the dication is stabilized even for the G0 dendrimer, presumably because of charge-transfer interactions. There are two competing channels to fragment in CID experiments: Higher generations prefer the loss of tweezer followed by some fragmentation of the viologen dication, whereas the lower generations first losoe one dendron arm and subsequently the tweezers: A clear dendritic effect which can not be observed in the solution due to the presence of stabilizing counterions which are absent in the gas phase.
