Organometallic palladium reagents for cysteine bioconjugation

Reactions based on transition metals have found wide use in organic synthesis, in particular for the functionalization of small molecules. However, there are very few reports of using transition-metal-based reactions to modify complex biomolecules, which is due to the need for stringent reaction conditions (for example, aqueous media, low temperature and mild pH) and the existence of multiple reactive functional groups found in biomolecules. Here we report that palladium(II) complexes can be used for efficient and highly selective cysteine conjugation (bioconjugation) reactions that are rapid and robust under a range of bio-compatible reaction conditions. The straightforward synthesis of the palladium reagents from diverse and easily accessible aryl halide and trifluoromethanesulfonate precursors makes the method highly practical, providing access to a large structural space for protein modification. The resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody–drug conjugates. These palladium complexes show potential as benchtop reagents for diverse bioconjugation applications.National Institutes of Health (U.S.) (GM-58160)National Institutes of Health (U.S.) (GM-101762)MIT Faculty Start-up FundDamon Runyon Cancer Research FoundationSontag Foundation (Distinguished Scientist Award)Massachusetts Institute of Technology. Dept. of Chemistry (George Buchi Research Fellowship)David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Fellowship in Cancer Research

Rectangular Coordination Polymer Nanoplates: Large-Scale, Rapid Synthesis and Their Application as a Fluorescent Sensing Platform for DNA Detection

In this paper, we report on the large-scale, rapid synthesis of uniform rectangular coordination polymer nanoplates (RCPNs) assembled from Cu(II) and 4,4′-bipyridine for the first time. We further demonstrate that such RCPNs can be used as a very effective fluorescent sensing platform for multiple DNA detection with a detection limit as low as 30 pM and a high selectivity down to single-base mismatch. The DNA detection is accomplished by the following two steps: (1) RCPN binds dye-labeled single-stranded DNA (ssDNA) probe, which brings dye and RCPN into close proximity, leading to fluorescence quenching; (2) Specific hybridization of the probe with its target generates a double-stranded DNA (dsDNA) which detaches from RCPN, leading to fluorescence recovery. It suggests that this sensing system can well discriminate complementary and mismatched DNA sequences. The exact mechanism of fluorescence quenching involved is elucidated experimentally and its use in a human blood serum system is also demonstrated successfully

Arene C-H borylation strategy enabled by a non-classical boron cluster-based electrophile.

Introducing a tri-coordinate boron-based functional group (e.g., boronic ester) into an unactivated C-H bond in the absence of directing groups is an ongoing challenge in synthetic chemistry. Despite previous developments in transition metal-catalyzed and -free approaches, C-H borylation of sterically hindered arenes remains a largely unsolved problem to date. Here, we report a synthetic strategy of a two-step, precious metal-free electrophilic C-H borylation of sterically hindered alkyl- and haloarenes to generate aryl boronic esters. The first step relies on electrophilic aromatic substitution (EAS) induced by cage-opening of Cs2[closo-B10H10], forming a 6-Ar-nido-B10H13 product containing a B-C bond, followed by a cage deconstruction of arylated decaboranes promoted by diols. The combination of these two steps allows for the preparation of aryl boronic esters that are hardly accessible by current direct C-H borylation approaches. This reaction does not require any precious metals, highly-engineered ligands, pre-functionalized boron reagents, or inert conditions. In addition, the unique properties of a non-classical boron cluster electrophile intermediate, B10H13+, afford a regioselectivity with unique steric and electronic control without the undesirable side reactions

A spray-drying strategy for synthesis of nanoscale metal-organic frameworks and their assembly into hollow superstructures

Metal-organic frameworks (MOFs) are among the most attractive porous materials known today. Their miniaturization to the nanoscale-into nanoMOFs-is expected to serve myriad applications from drug delivery to membranes, to open up novel avenues to more traditional storage and catalysis applications, and to enable the creation of sophisticated superstructures. Here, we report the use of spray-drying as a versatile methodology to assemble nanoMOFs, yielding spherical hollow superstructures with diameters smaller than 5 μm. This strategy conceptually mimics the emulsions used by chemists to confine the synthesis of materials, but does not require secondary immiscible solvents or surfactants. We demonstrate that the resulting spherical, hollow superstructures can be processed into stable colloids, whose disassembly by sonication affords discrete, homogeneous nanoMOFs. This spray-drying strategy enables the construction of multicomponent MOF superstructures, and the encapsulation of guest species within these superstructures. We anticipate that this will provide new routes to capsules, reactors and composite materials. © 2013 Macmillan Publishers Limited. All rights reserved.I.I. and M.C.S. thank MICINN and ICN for a Ramón y Cajal grant and a research contract, respectively. A.C. thanks the Generalitat de Catalunya for a FI fellowship.Peer Reviewe