Over the past month or two several reviews have been published which mention or have fluorous sections within them. None of these reviews are dedicated to fluorous techniques, but rather to other topics where fluorous methods are just a part. These types of reviews, while not necessarily detailed, can provide a good sense of where methods fit within the overall landscape of a given research field. We’ll briefly describe each of these reviews and where fluorous fits in.
“Lesser-Known Enabling Technologies for Organic Synthesis”, O’Brien, M.; Denton, R.; Ley, S.V., Synthesis, 2011, 1157. This review summarizes emerging technologies and methods in separations and synthesis of small molecules. The bulk of the review covers “phase-switching” methods, all of which generally aim to provide solution phase chemistry with solid phase-like separation. The authors rightfully note that a key driver of this concept was fluorous chemistry and the use of fluorous solid phase extraction (FSPE) and fluorous liquid-liquid extraction (FLLE). They don’t spend much ink describing fluorous methods compared to other phase-switching strategies, probably because it’s not as lesser-known and due to the number of published reviews dedicated to fluorous chemistry. It’s nice to compare however some of the other methods and one can see that most of them require either another reaction, e.g. polymerization, or require functionalities, such as basic amines, which could be non-orthogonal with the desired molecule. Fluorous tags don’t require any additional reactions, are orthogonal to other functional groups, and are compatible with a complete range of chemistries.
(By the way, there were also some sections on low temperature and reflux chromatography methods which were interesting, but I don’t see how I would use them in the lab. It seems like it would be very tough to do that on analytical scale to develop method for preparative scale.)
“Chemistry and Glycobiology”, Wu, C.-Y.; Wong, C.-H., Chem. Comm. 2011, DOI: 10.1039/c0cc04359a. This is one of the “Highlight” papers, a mini-review, that Chemical Communications publishes on a topic of interest, in this case glycobiology. This short paper has three sections; synthesis of glycoproteins, glycan arrays, and probing glycosylation post-translational modifications. In each section various methods and challenges are summarized. For example, in the glycan array section the authors first address the issue of glycan probe synthesis then move on to array formation and characterization. While no mention of fluorous based synthesis of carbohydrates was made (surprisingly), they did mention DIOS, NIMS, and fluorous aluminum coated glass based arrays which are used for matrix-free MS analysis of glycan arrays. This highlight paper does provide the chemist a nice sense of some of the importance and challenges of glycobiology.
“Lab-On-A-Plate: Extending the Functionality of MALDI-MS and LDI-MS Targets”, Urban, P.L.; Amantonico, A.; Zenobi, R., Mass Spec. Rev. 2011, 435. In this review the authors focus on the use of MALDI and matrix-free laser desorption/ionization (LDI) MS targets as more than just sample supports for MS, but as platforms for sample preparation such as enrichment, digestion, purification, etc. The review is organized by laboratory process. For example, sections include preconcentration, sample enrichment, biological reactions, etc. Fluorous techniques, once again in the form of NIMS analysis, is included in the Enzyme-based Methods section highlighting the substrate immobilization on the NIMS surface through fluorous partitioning. The fluorous DIOS method of on-target enrichment was not mentioned, although it would certainly fit. Interestingly, the review includes a number of tables listing the various modified MALDI and LDI targets which have been used. Several of these are Teflon or other perfluorinated coated surfaces which might be amenable to immobilizing fluorous-tagged molecules and thereby allowing for on-target processing as has been done with NIMS and DIOS.
“Small Molecule Microarrays: The First Decade and Beyond”, Wu, H.; Ge, J.; Uttamchandani, M.; Yao, S.Q., Chem. Comm. 2011, DOI: 10.1039/c1cc11464f. Speaking of immobilizations, here’s another Chem. Comm Highlights paper which summarizes the efforts in small molecule microarrays (SMMs) over the last decade. The paper describes SMM formation and design concentrating on surface modification and attachment of the small molecules then goes on to summarize some of the application of small molecule microarrays. Fluorous immobilization is one of only 3 non-covalent methods cited with the other two being hydrogen bonding and physical entrapment. The work of Profs. Pohl, Schreiber, and Spring are cited. In terms of applications, the Schreiber group found small molecule inhibitors of HDAC enzymes, while the Pohl group has identified unique binding modes for ConA lectin. Both groups used fluorous modified slides. What wasn’t mentioned in the review is how fluorous tags can be used to facilitate synthesis, purification, and immobilization. So unique among the methods mentioned, fluorous facilitates the synthesis and purification of the target probes and is used for the array formation.
Each of the above reviews has been published in the last month or two and together they show just how broad and useful fluorous methods can be. From synthesis, analysis, separation, and immobilization.