Noteworthy Chemistry

August 22, 2011

Here’s how to make a “wet” fullerene. Water molecules are usually found in clusters because of their high degree of hydrogen bonding in bulk. Finding a single molecule of water that is not hydrogen-bonded to itself or other molecules is rare.

Because of their spherical shapes and their sizes, fullerenes are suitable cages for water molecules. To encapsulate water inside fullerenes, however, requires harsh conditions. K. Kurotobi and Y. Murata at Kyoto University (Japan) report a synthetic method for trapping a single water molecule inside fullerene C60.

In the authors’ “surgical” method, an opening is made in C60 (1) by treating it with a diarylpyridazine (2) followed by cleavage of a double bond with oxygen to give 3 and further oxidation with N-methylmorpholine oxide (NMMO) to produce 4. Water is then inserted into the cage at 120 °C and 9000 atm pressure (5). Finally, the cage is regenerated by being reduced with a phosphite ester (6) and then heated in the presence of alumina to give “wet” fullerene (7).

Single-crystal x-ray analysis verifies that the C60 cage has water encapsulated in it, and the oxygen atom is located in the center. The water molecule does not affect the structure of the cage. Water remains inside the fullerene even after heating to 420 °C under vacuum.

Mass spectrometry shows a parent ion peak for C60H2O, and its proton NMR spectrum has a singlet peak at –4.81 ppm, confirming the shield effect of the cage. The water-encapsulated fullerene can be separated from C60 by using HPLC. Whereas C60 is nonpolar, density functional theory calculations show that 7 should have a dipole moment of 2.03 D, almost the same as water. The compound can be thought of as a “polar C60”. (Science 2011, 333, 613–616; JosÉ C. Barros)

Examine the mother liquors after a classical resolution. During the course of improving the synthesis of carmegliptin, a dipeptidyl peptidase IV inhibitor for treating type 2 diabetes, A. Fettes and co-workers at F. Hoffman-La Roche (Basel, Switzerland) sought a better way to resolve a racemic enamine intermediate. Resolution with (S,S)-dibenzoyltartaric acid proceeds with high diastereomeric ratio (>99.5:0.5 dr) and good yield (45%). The mother liquors from the resolution, however, are virtually racemic instead of rich in the unwanted diastereomer.

This observation spurred the authors to develop a crystallization-induced dynamic resolution. The resolution is carried out at 60 °C in EtOH and produces the desired salt in 93% yield without reducing the dr. It is likely that the racemization of the unwanted isomer in solution proceeds through ring-opened intermediates. (Org. Process Res. Dev. 2011, 15, 503–514; Will Watson)

Aggregated “simple” luminogens emit bright red light. Scientists are developing luminescent molecules that emit intensely in the solid state. They are looking at a class of novel luminogenic molecules with aggregation-induced emission enhancement (AIEE) characteristics; their solid aggregates emit more efficiently than their dilute solutions. These molecules, however, are still limited in the variety of emitted colors. Many luminesce in the short-wavelength region; blue and green emissions are the most common.

A team of researchers led by P. Wang at the Technical Institute of Physics and Chemistry (Beijing) and C.-S. Lee at the City University of Hong Kong developed new luminogenic molecules that emit strongly in the aggregated state. Their emission spectra peak at wavelengths as high as 617 nm.

An example of the luminogen molecules is shown in the figure. Luminogen 1 has a simple molecular structure and is readily synthesized. Whereas a MeOH solution of 1 is almost nonluminescent and has a negligible fluorescence quantum yield (<0.09%), its aggregates in an aqueous medium and its crystalline solid powders emit bright red light with ≈150-fold higher efficiency.

The authors believe that the pronounced AIEE effect of 1 is the result of aggregate formation restricting the intramolecular rotations of its amino, benzyloxy, and malononitrile rotors. Molecules of 1 readily self-assemble into highly emissive microtubules via a simple precipitation process. (CrystEngComm 2011, 13, 4617–4624; Ben Zhong Tang)

Engineer a useful polypeptide from resilin, elastin, and collagen. A. Pepe and coauthors at the University of Basilicata (Potenza), the Institute of Biophysics of the National Research Council of Italy (Genoa), the University of Catania, and the University of Naples Federico II (all in Italy) developed nature-inspired biomaterials with an eye toward tailored biological and mechanical function.

The authors used a recombinant DNA technology, recursive directional ligation, to synthesize the resilin–elastin–collagen (REC)–like polypeptide. Lysine residues were encoded to insert cross-linking sites for forming a 3-D scaffold. The conformation of the REC-like biomaterial simulated that of a polyproline II left-handed helix in water at 0 °C. In 2,2,2-trifluoroacethanol, the material consists of a mixture of β-turns and random coils.

When the polypeptide is incubated for 3 days in water at 37 °C, its fibrillar microstructures aggregate into stable, aligned bundles. Increasing the temperature enhances the propensity to form higher-order superstructures from the globular REC oligomers. Elasticity models predict Young’s moduli values between 0.1 and 3 MPa for the self-assembled REC incubated at 37 °C. (Biomacromolecules 2011, 12, 2957–2965; LaShanda Korley)

Self-assembled polymer-based micelles appear stable in serum. Polymeric nanoparticles are useful as carriers for drug delivery. Two advantages are that they can overcome the limited aqueous solubility of a variety of hydrophobic drug molecules and increase the serum half-life for improved drug efficacy.

J. Lu, S. C. Owen, and M. S. Shoichet* at the University of Toronto previously reported that amphiphilic copolymer poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol) (1) self-assembles into nanosized micelles (Lu, J.; Shoichet, M. S. Macromolecules 2010, 43, 4943–4953). They now describe using these nanoparticles to encapsulate Forster resonance energy transfer (FRET) structure pairs, which allows an efficient assessment of particle stability in serum.

The FRET pairs consist of a donor molecule, 3,3’-dioctadecyloxacarbocyanine perchlorate (2), and the corresponding acceptor, 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (3). The procedure works by following the release of the FRET pair from the micelle with fluorescence. The authors then used FRET-based methods to track the stability of the resulting micelles (4)—which contain encapsulated pairs—in the presence of individual serum proteins or in complete serum.

This unique analytical system combines FRET, fast protein liquid chromatography, and dynamic light-scattering methods. A key use of this technique is to measure micelles’ kinetic stability—an indicator of whether encapsulated particles such as drug molecules will “leak” out of the micelles in biological media over time.

The results suggest that 4 has excellent stability in the presence of serum. The authors also used a hemolysis assay to verify that 4 is compatible with red blood cells. The accumulated results suggest that the micelles are stable in vivo, a critical requirement for intravenous drug delivery applications. (Macromolecules 2011, 44, 6002–6008; W. Jerry Patterson)

Use proton NMR to determine polymer molecular weights. NMR spectroscopy is used in polymer science to determine properties such as chain microstructure, polymer tacticity, and monomer sequences. Gel permeation chromatography (GPC) is widely used to measure polymer molecular weights (MWs). Computing MWs is routinely based on the MW values of certain polymeric standards.

But with GPC, polymers are separated on the basis of hydrodynamic volume, not MW, and appropriate calibration standards are not always available. Therefore, NMR, which can determine absolute MW values, may be superior to GPC. J. U. Izunobi and C. L. Higginbotham* at the Athlone Institute of Technology (Ireland) report a proton NMR method for determining polymer MWs.

The authors developed equations that establish the relationship between number-average molecular weight (Mn) and the area under the resonance peaks in the NME spectrum. To help explain the theory, they give examples for calculating the Mns of a homopolymer and a block copolymer. The authors emphasize that accuracy in assigning and integrating the peaks is essential for the calculations. They also specify the limitations of this method.

This protocol should be useful for undergraduate and graduate students who are studying chemical characterization techniques. (J. Chem. Educ. 2011, 88, 1098–1104; Sally Peng Li)

Why do time-of-flight mass spectrometers have mass range limits? In theory, time-of-flight mass spectrometry (TOF-MS), which removes the expansion-induced kinetic energy by collisional cooling, allows the ions to travel along the ion guide axes without significant deviation. This ensures that ions are injected into the analyzer in a well-collimated beam with well-defined kinetic energy. If the ions can be injected into an orthogonal acceleration (oa) TOF mass analyzer in this manner, high-resolution mass analysis should be obtained regardless of mass or mass-to-charge ratio (m/z).

J. Lee and P. T. A. Reilly* at Washington State University (Pullman) used this technique, but they did not obtain high-resolution spectra for ultrahigh-MW ions. They studied the deterioration of resolution and mass accuracy of TOF mass analyzers with increasing mass after the expansion-induced kinetic energy was eliminated by collisional cooling in an ion guide.

Their analysis indicates that the effusive 30–40 mTorr expansion that occurs at the exit of the first ion guide into a vacuum causes a mass-related decrease in resolving power (mm). For smaller ions with molecular weights of a few kilodaltons, the collision cross-section is sufficiently small that very few collisions occur during the expansion. Because the difference in velocity between the ion and the carrier gas is sufficiently small, collisions that do occur do not significantly alter the trajectories of the ions into the next guide. The radial excitation that does occur as the small ions are expanded into the first guide is quickly damped, and the small ions travel along the central axes of the guides to be injected into the oa-TOF in highly collimated trajectories to allow high-resolution mass analysis (upper trace in the figure).

Larger ions, however, have larger collision cross-sections and collide more during the effusive expansion. They also move correspondingly more slowly so that the difference in velocity between a large ion and the carrier gas is much greater; the momentum transferred (mΔv) with each collision is also greater. Each collision is more effective at altering the trajectory of the larger ions; and after a large ion’s expansion-induced radial motion is damped in the first ion guide, the effusive expansion creates dispersive trajectories into the next ion guide.

The pressure in subsequent guides is too low to provide effective damping. The radial excitation induced by the dispersive trajectories out of the first guide, therefore, is maintained throughout the system of ion guides, thereby generating dispersive trajectories into the oa-TOF and poorly resolved mass analysis (lower trace). (Anal. Chem. 2011, 83, 5831–5833; Gary A. Baker)

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