February 3, 2014
- Now iron also does the “magic”
- Peptides allosterically modulate conformation of HIV gp120
- What happens when crude oil is exposed to sunlight?
- Were balms used in pharaonic meat mummies?
- Are you measuring binding constants correctly?
- Make sugar-coated anhydrobiotic supported membranes
Now iron also does the “magic”. Hydrogen, a high-efficiency fuel with low environmental impact, is expected to become the major energy source in the next generation of clean-energy technology. But hydrogen storage is a problem that has not been solved. Methanol, which has a hydrogen content of 12.6 wt%, can be considered a hydrogen storage medium; but releasing hydrogen from methanol, called methanol reforming, often requires high-temperature heterogeneous catalysts or expensive noble-metal–based catalysts.
To reform methanol under mild conditions at low cost, M. Beller and coauthors at the Leibniz Institute for Catalysis at the University of Rostock (Germany) and the Institute of Biomolecular Chemistry, CNR (Sassari, Italy) developed an iron-based catalyst that promotes methanol dehydrogenation at low temperatures.
The authors prepared complex 3, a Fe(II)-based hydrido hydroborato pincer-type catalyst, by treating dibromo complex 2 with NaBH4 in base. Complex 2 was obtained by coordinating amine 1 to FeBr2·(THF)2, followed by CO insertion.
At 91 °C, in a 9:1 v/v MeOH–H2O mixture that contained 8 M KOH, 4.18 μmol of complex 3 catalyzed hydrogen release. The turnover frequency (TOF) was 702 h–1 in the first hour and gradually decreased to 510 h–1. The maximum turnover number (TON) over 43 h was 6270. When the catalyst loading was lowered to 1 μmol, the stability of 3 appeared to improve; it gave a third-hour TOF of 617 h–1 and a TON of 9834 over 46 h.
The authors believe that amide complex 4 is the catalytically active species in the transformation; it would be formed from 3 by the loss of H+ and BH4–. This work is an example of using an earth-abundant metal–based complex for reforming methanol under mild conditions; it may open an avenue to low-cost, practical catalysts that could be used in methanol-reformation fuel cells. (Angew. Chem., Int. Ed. 2013, 52, 14162–14166; Xin Su)
Peptides allosterically modulate the conformation of HIV gp120. For HIV-1 to infect CD4 positive (CD+) cells, the viral envelope protein gp120 must bind the cellular receptor CD4. This binding induces conformational changes that form CD4-induced (CD4i) epitopes. One CD4i epitope allows gp120 to bind a second receptor, CCR5 or CXCR4, which causes additional conformational rearrangements and allows HIV to enter and infect the CD4+ cell.
Monoclonal antibodies (mAbs) that target CD4i epitopes and the CD4 binding site (CD4bs) are generated in HIV-1–infected individuals who can suppress the virus naturally. A focus of HIV prophylactic vaccine design is targeting B-cell responses to the conserved CD4bs and CD4i epitopes, but the virus suppresses their immunogenicity by reducing their accessibility. The concealed conserved surfaces must be more effectively exposed for successful vaccine development.
Previous methods that stabilize the gp120:CD4 complex allow the constitutive presentation of CD4i epitopes but block the CD4bs and prevent the epitopes’ antigenicity. J. M. Gershoni and coauthors at Tel Aviv University and the University of Maryland School of Medicine (Baltimore) produced targeted phage display libraries for sequential screening and optimization of gp120 peptide modulators that interact with the HIV viral envelope and expose CD4i epitopes that are recognized by antibodies. These peptides allosterically induce conformational rearrangements that are typical of the CD4 bound state while keeping CD4bs accessible to antibodies.
Selected peptides must bind to the HIV-1 envelope in the absence of CD4 and induce binding to stringent CD4i mAbs (e.g., CG10), which do not recognize gp120 unless it is bound to CD4. The authors screened a random phage display peptide library by using lab-adapted HIV-1 gp120 as bait. Multiple rounds of biopanning led to the isolation of a phage designated m1 (amino acid sequence: C-DRRDLPQWAKRE-C), which bound to gp120 and allowed CG10 binding that indicated the induction of CD4i epitopes.
Further experiments showed that CD4 and m1-phage have different, distinct epitopes on the HIV envelope and simultaneously bind gp120. To identify a higher affinity peptide, the authors constructed a second-generation screening library by using biased random mutagenesis. They isolated the m2-phage C-DRRDLPDWAIRA-C, which induced the binding of multiple stringent CD4i mAbs and allowed the binding of three CD4bs mAbs. This result indicates that m2 binds an epitope on the HIV envelope that is distinct from CD4 and CD4bs mAbs.
The authors used results from the second screen to identify a shared six-residue core motif that induced the CD4i conformation that was assumed to be critical for gp120 binding specificity. They then produced a third library to optimize the variable positions and isolated the m3 peptide C-SRSDLPEWAVRT-C. Surface plasmon resonance binding assays showed that all three phage-displayed peptides have no affinity for CG10 but bind gp120, which induces CG10 binding.
The phage-displayed peptides m1, m2, and m3 lock the HIV envelope into a CD4 bound state and allow the simultaneous exposure of CD4i epitopes and functional CD4bs. This may be valuable for designing a gp-120 based immunogen. (Retrovirology 2013, 10, No. 147; Abigail Druck Shudofsky)
What happens when crude oil is exposed to sunlight? As the worldwide consumption of petroleum increases, producers are using lower quality petroleum to meet the demand. Heteroatomic species in low-quality petroleum (e.g., sulfur-, nitrogen-, and oxygen-containing compounds) can poison catalysts during refining, corrode containers and pipes, and damage the environment when they are released by petroleum fuel combustion or by spills and leakage during transport.
Exposing petroleum to sunlight produces changes that affect its solubility and toxicity. M. P. Barrow and co-workers at the University of Warwick (Coventry, UK) simulated the effects of exposing crude oil to sunlight and studied the results by using Fourier transform ion cyclotron resonance mass spectrometry coupled with atmospheric pressure photoionization (APPI). They found that this technique is well suited to analyzing complex mixtures such as crude oil, especially when they monitored the effects of a particular process on the entire mixture.
The authors used a light-sour crude oil standard reference material obtained from the National Institute of Standards and Technology. Solar radiation was simulated by using a 35-W SoLux halogen bulb, which closely mimics natural sunlight. They compared the results with those obtained with a 4-W UV light and a control sample that was shielded from light. The samples were analyzed after 938 h (≈5.5 weeks) of exposure.
The postexposure analysis showed that the control sample changed very little, and the sample exposed to the UV source became more viscous. The sample exposed to the SoLux source resembled a solid more than a liquid, and it exhibited the greatest composition change. Compounds that contained heteroatoms underwent photo-oxidation more readily than did hydrocarbons. Oxygen-containing species increased, but nonoxygenated sulfur- and nitrogen-containing species decreased significantly, indicating photoinduced oxidation. The oxygen-containing species may be acidic, soluble, and bioavailable; and therefore it is potentially toxic in a marine environment.
Reactivity was more closely associated with compound class and the number of double-bond equivalents than with carbon number. Compounds with fewer double bonds were more reactive, with some exceptions. The hydrocarbon components were highly stable. The polyaromatic hydrocarbons were especially stable, making them good markers for the origins of spilled or leaked petroleum after prolonged exposure to the environment. (Anal. Chem. 2014, 86, 527–534; Nancy McGuire)
Were balms used in pharaonic meat mummies? One of the most important items in ancient Egypt burials was food to sustain the deceased in the afterlife. Most of the food that has been found in these tombs was preserved by dehydrating it with salt (NaCl) and natron (Na2CO3); it was then wrapped and placed in the coffin.
Meat was prepared similarly to other foods, but it also may have been treated with organic balms in a process that was similar to preserving human or animal mummies. Many such “meat mummies” have been found, but little attention has been given to discovering how they were preserved.
R. P. Evershed and coauthors at the University of Bristol (UK) and the American University at Cairo (New Cairo, Egypt) studied several samples of meat mummies: beef ribs, calf, duck, and goat from the Cairo and British museums. They subjected the samples to gas chromatography coupled with combustion isotope ratio mass spectrometry (GC–C-IRMS) and used δ13C values to assign the origins of organic compounds.
The results showed that fatty acids, diacids, and dihydroxy acids, but not wax or resin, were added to the wrappings of the calf meat mummy. The same profile was found in the goat sample, but the duck sample contained no lipids. The beef ribs contained a mixture of fat, oil, and Pistacia resin. (Pistacia is a genus of flowering plants in the cashew family.) The resin was detected by the presence of the triterpenoids oleanonic and isomasticadienoic acids and their oxidization products.
The presence of the beef balm is noteworthy because it has not been described previously. The authors believe that it may be exclusive to meat mummies because it is known to be a food flavor. This study shows that sophisticated processes were used to embalm foods in addition to bodies. (Proc. Natl. Acad. Sci. USA 2013, 110, 20392–20395; José C. Barros)
Are you measuring binding constants correctly? How alkali metal cations (salt effects) in buffer solutions influence the microcalorimetric binding constants between p-sulfonatocalixarene (SC4, 1) and guest molecules has long been debated. The versatile water-soluble macrocycle SC4 is used to build supramolecular complexes with a variety of guest molecules. Although researchers have observed salt effects associated with SC4 and cations in buffer solutions for many years, they are thought to have negligible influence on calorimetric determinations of the affinity of SC4 toward guest molecules.
Because SC4 is pervasive in supramolecular chemistry, it is crucial to determine the actual influence of salt effects on experiments that measure thermodynamic properties of SC4 complexes. L. García-Río and coauthors at the University of Santiago (Spain) and Jacobs University Bremen (Germany) used isothermal microcalorimetry to measure how salt effects influence SC4 binding at neutral pH.
The authors studied the association between SC4 and several mono- and divalent cations such as alkali metal and alkaline earth cations and NH4+. They propose a sequential binding model for Na+ and an ion-exchange binding model for the other cations. They also show that binding between SC4 and simple alkali metal cations is driven by entropy rather than enthalpy, as was believed previously.
This study uncovers largely underestimated salt effects in SC4 binding. For example, the binding constant between SC4 and Na+ is ≈102 M–1, which should be considered when interpreting complexation data measured in sodium phosphate buffers. Because these salt effects are not limited to SC4, chemists who work with receptors in buffer solutions need to understand how salt effects influence binding constants. (Chem.—Eur. J. 2013, 19, 17809–17820; Xin Su
Make sugar-coated anhydrobiotic supported membranes. Inspired by anhydribiosis—a sugar-vitrification method that several organisms use to survive extreme dehydration—A. N. Parikh and co-workers at the University of California, Davis, devised a hydration-induced assembly method for preparing supported membranes. They used vitrified trehalose as a protective coating and cargo container for lipid vesicles and proteins on a synthetic substrate. The dry, vitrified state is stable for many weeks until it is rehydrated to release the cargo and unmask the substrate.
The authors derivatized glass substrates with spatial arrays of n-octadecyltrichlorosilane (OTS). They then deposited a trehalose solution that contained preformed unilamellar vesicles doped with a fluorescent lipid conjugate onto the hydrophilic patterned substrate to form stable sugar-protected films. Exposure to water triggers cargo release and promotes fusion and assembly of the vesicles onto the patterned surface. The assembled vesicles form monolayers on the OTS sections and bilayers on the untreated spaces.
Additional features of this strategy include the ability to monitor and control interactions between multiple cargo elements and the inclusion of membrane receptors via proteoliposomes. (J. Am. Chem. Soc. 2014,136, 60–63; LaShanda Korley)