Stephen J. Lee

Conformationally Gated Electrochemical Gene Detection

The synthesis and characterization of a 26‐base DNA hairpin containing both a redox‐active reporter (ferrocene) and terminal thiol functionality for electrochemical gene detection is described. This electrochemical DNA sensor exploits electron‐transfer dynamics that alter as a consequence of a large structural rearrangement (hairpin‐to‐duplex) induced by hybridization of the target DNA sequence. Melting temperature and circular dichroism studies confirm that the 26‐mer DNA forms a hairpin structure in the absence of target DNA. The loop region of the DNA hairpin is shown to form a stable duplex in the presence of complementary single‐stranded DNA. Atomic force microscopy and ellipsometry experiments of immobilized self‐assembled DNA monolayers suggest that hybridization with complementary DNA affords a conformational change that alters the electrochemical response.

Constitutionally selective amplification of multicomponent 84-membered macrocyclic hosts for (−)-cytidine•H+

Mixtures of dipeptide monomers create stereochemically and constitutionally complex dynamic libraries of potential receptors. When (−)-cytidine was utilized as guest an 84-membered cyclic host was amplified (70–175 fold) from a nearly undetectable initial concentration. Only the specified diastereomeric combination of the two chiral building blocks yielded a dynamic library from which the macrocyclic receptor could be amplified.

Deracemization of a Dynamic Combinatorial Library Induced by (–)-Cytidine and (–)-2-Thiocytidine

A dynamic combinatorial library composed of racemic hydrazone-based dipeptides becomes deracemized on binding to the chiral analytes (-)-cytidine and (-)-2-thiocytidine through the amplification of two receptors, (SS)-dimer and (RRRR)-tetramer. The deracemization phenomenon was investigated by laser polarimetry, mass-tagged pseudo-enantiomers in conjunction with electrospray ionization mass spectrometry, HPLC/UV-MS, UPLC/UV-MS, rapid-resolution LC-MS, collision-induced dissociation MS/MS, and numerical simulations. These data were consistent with a phenomenon where (SS)-dimer and (RRRR)-tetramer selectively bind the chiral analyte in preference to their enantiomeric counterparts, which ultimately causes them to be amplified and the library to become deracemized.

The effect of gas-phase reactions on the quantitation of cyclic hydrazone libraries by electrospray ionization (ESI) mass spectrometry

Using mass spectrometry coupled with LC analysis we report evidence of diastereomer dependent fragmentation and oligomerization reactions in the ionization of acyl-hydrazone-based libraries of cyclic oligomers. These effects can significantly affect the accuracy of MS-based quantitations, but also provide a venue for examining ionization effects in dynamic combinatorial libraries (DCLs).

Thiourea-catalyzed aminolysis of N-acyl homoserine lactones

Thiourea catalysts accelerate aminolysis of N-acyl homoserine lactones (AHLs), molecules integral to bacterial quorum sensing. The catalysts afford rate enhancement of up to 10 times the control in CD(3)CN. Mild catalysis in other polar aprotic solvents is still observed, while the activity is attenuated in polar protic solvents.

Gold(I) Catalyzed Dearomative Claisen Rearrangement of Allyl, Allenyl Methyl, and Propargyl Aryl Ethers

Claisen rearrangements of allyl aryl ethers to generate enones bearing all carbon quaternary centers are accelerated by Ph3PAuNTf2 under mild conditions in good yields. Multiple C-C bond containing variants of the allyl fragment are viable, including alkylidenecyclopropanes, allenes, and alkynes, which generate all-carbon stereogenic centers substituted with vinyl cyclopropanes, 1,3-butadienyl, and allenyl substituents, respectively, for subsequent synthetic manipulation. With allyl phenyl ethers, the product of the [3,3] rearrangements can be trapped by a tandem [4 + 2] cycloaddition to generate complex molecular scaffolds from readily available, achiral starting materials.

Chemoselective amide reductions by heteroleptic fluoroaryl boron Lewis acids

The heteroleptic borane catalyst (C6F5)2B(CH2CH2CH2)BPin is found to hydrosilylatively reduce amides under mild conditions. Simple tertiary amides can be reduced using Me2EtSiH, whereas tertiary benzamides required a more reactive secondary silane, Et2SiH2, for efficient reduction. The catalytic system described exhibits exceptional chemoselectivity in the reduction of oligoamides and tolerates functionalities which are prone to reduction under similar conditions.