Synthesis and Conformational Switching of Partially and Differentially Bridged Resorcin[4]arenes Bearing Fluorescent Dye Labels. Preliminary Communication

J. Am. Soc. Mass Spectrom.

Frankevich

et al. 2005

Fluorescence resonance energy transfer (FRET) is a distance-sensitive method that correlates changes in fluorescence intensity with conformational changes, for example, of biomolecules in the cellular environment. Applied to the gas phase in combination with Fourier transform ion cyclotron resonance mass spectrometry, it opens up possibilities to define structural/ conformational properties of molecular ions, in the absence of solvent, and without the need for purification of the sample. For successfully observing FRET in the gas phase it is important to find suitable fluorophores. In this study several fluorescent dyes were examined, and the correlation between solution-phase and gas-phase fluorescence data were studied. he study of biomolecular conformation in the gas phase has attracted great attention because it opens possibilities to compare gas-phase and solution-phase structures and to understand the effect of the solvent on a molecule. Because matrix-assisted laser desorption/ionization (MALDI) [1] and electrospray ionization (ESI) [2] typically generate unsolvated ions without any adducts, their structure also provides an ideal model system for theoretical calculations of conformations. A major question today is whether singly or multiply charged biomolecular ions produced by soft ionization methods retain their native (or at least a "native-like"), active conformation in the gas phase. This is often assumed but needs to be proven rigorously.Mass spectrometry has many attractive features for studying biomolecules in the gas phase, including the capability of the isolation of ions and elimination of unwanted species before detection and a positive identification of the molecule from the exact mass or from tandem mass spectrometry (MS/MS) data. There are mass spectrometric methods available for obtaining conformational information of molecules in the gas phase: blackbody infrared radiative dissociation where ions undergo unimolecular dissociation by exchanging their energy with the surroundings by absorption and emission of infrared photons [3], collision-induced dissociation where ions are dissociated as a result of interaction with a target neutral species [4], hydrogendeuterium exchange where hydrogen atoms of the protein are exchanged with the deuterium atoms from a solution [5], covalent or noncovalent tagging of biomolecules based on the surface accessibility of specific moieties [6,7], and ion mobility spectrometry where the measured cross section of the molecule is compared with a theoretically calculated cross section [8]. However, generally speaking, these methods yield only indirect information about the gas-phase conformation, which is often derived from either the overall cross section of the molecule, from a fragmentation pattern, or from a dissociation rate.Recently, the efficient trapping capabilities of mass spectrometry have been coupled with the high sensitivity of fluorescence detection to provide structural and spectroscopic information of molecules in the gas phase. The general idea...

Section: Bodipy Dyementioning

confidence: 99%

Clear evidence of fluorescence resonance energy transfer in gas-phase ions

Dashtiev

J. Am. Soc. Mass Spectrom.

Frankevich

et al. 2005

“…Here, we present a detailed study of the temperature-and pH-triggered vase 3 kite conformational switching of these systems (for a preliminary report on parts of this work, see [7]). By variable-temperature NMR (VT-NMR) spectroscopy, we discovered a new interconversion between two kite forms (kite 1 and kite 2; Scheme 1) and estimated the thermodynamic (DH and DS) and kinetic parameters (DH = and DS = ) for the equilibration between the three (vase, kite 1, and kite 2) conformational states.…”

mentioning

confidence: 99%

NMR Investigations into the Vase‐Kite Conformational Switching of Resorcin[4]arene Cavitands

Jaun

Diederich

2004

Helvetica Chimica Acta

Self Cite

Dedicated to Professor K. N. Houk at the occasion of his 60th birthdayWe report the detailed investigation of temperature-and pH-triggered conformational switching of resorcin [4]arene cavitands 1 ± 10 (Figs. 1, 8, and 9). Depending on the experimental conditions, these macrocycles adopt a vase conformation, featuring a deep cavity for potential guest inclusion, or two kite conformations (kite 1 and kite 2) with flat, extended surfaces (Schemes 1 and 2). The thermodynamic and kinetic parameters for the interconversion between these structures were determined by variable-temperature NMR (VT-NMR) spectroscopy (Figs. 2 ± 7 and 10, and Tables 1 and 2). It was discovered that vase 3 kite switching of cavitands is strongly solvent-dependent: it is controlled not only by solvent polarity but also by solvent size. Conformational interconversions similar to those of the parent structure 1 with four quinoxaline flaps are also observed when the octol base skeleton is differentially or incompletely bridged. Only octanitro derivative 2 was found to exist exclusively in the kite conformation under all experimental conditions. The detailed insight into the vase > kite conformational equilibrium gained in this investigation provides the basis for the design and construction of new, dynamic resorcin[4]arene cavitands that are switchable between bistable states featuring strongly different structures and functions.1. Introduction. ± Resorcin[4]arene cavitands with four quinoxaline bridges were originally introduced and studied by Cram and co-workers [1]. A particulary interesting feature of these systems is their ability to switch between two states, a vase conformation with a deep cavity well suitable for guest inclusion [2] (for a review on molecular encapsulation, see [3]) and a kite conformation featuring a large flat surface. This vase > kite equilibrium is controllable by both temperature-[1] or pHvariation [4], and resembles the movement of a molecular gripper. According to Cram and co-workers, the temperature dependence of the vase > kite equilibrium is caused by solvation effects: at low temperatures, solvation of the larger, solvent-exposed surface favors the kite conformer, whereas, at higher temperature, the entropic term TDS solv for solvation of the larger kite surface becomes unfavorable, and the vase conformation predominates.We are interested in the potential utilization of modified resorcin[4]arene cavitands as molecular grippers, capable of guest hosting and releasing on demand, in device construction at the single-molecule level. This objective requires a deeper mechanistic understanding of the vase > kite conformational equilibration. In this context, the discovery of pH-triggered vase 3 kite switching and the use of UV/VIS spectroscopy to monitor the interconversion had been reported earlier [4] (for a first scanning tunneling microscopy (STM) study, imaging the vase conformation at molecular

“…Partial and unsymmetrical bridging of the resorcin [4]arene bowl (for a review on resorcin [4]arenes, see [6]) greatly expands the range of dynamic cavitands. A series of derivatives bearing fluorescent −borondipyrromethene×(BODIPY) dyes [7] attached to the upper rim of the cavitand walls were prepared for mechanistic investigations of the switching dynamics by polarization-resolved single-molecule microscopy [8] (for a preliminary report on parts of this work, see [9]). The solid-state structures of cavitands in both vase and kite conformations are also described.…”

mentioning

confidence: 99%

Functionalized and Partially or Differentially Bridged Resorcin[4]arene Cavitands: Synthesis and Solid‐State Structures

Skinner

Yamakoshi

et al. 2003

Helvetica Chimica Acta

Self Cite

Dedicated to Professor Duilio Arigoni on the occasion of his 75th birthdayWe report the synthesis and structural characterization of modified Cram-type, resorcin[4]arene-based cavitands. Two main loci on the cavitand backbone were selected for structural modification: the upper part (wall domain) and the lower part (legs). Synthesis of unsymmetrically bridged cavitands with different wall components (i.e., 7, 8, and 14 ± 18) was performed by stepwise bridging of the four couples of neighboring, Hbonded OH-groups of octol 1a (Schemes 1, 2, 4, and 5). Cavitands with modified legs (i.e., 20, 24, 27, and 28), targeted for surface immobilization, were synthesized by short routes starting from suitable aldehyde starting materials incorporating either the fully preformed leg moieties or functional precursors to the final legs (Schemes 7 ± 10). The new cavitand substitution patterns described in this paper should enable the construction of a wide variety of functional architectures in the future. X-Ray crystallography afforded the characterization of cavitands 2c (Fig. 3) and 24 (Fig. 7) in the vase conformation, with 2c featuring a well-ordered CH 2 Cl 2 guest molecule in its cavity. A particular highlight is the X-ray crystal-structure determination of octanitro derivative 19 (Scheme 6), which, for the first time, shows a cavitand, lacking substituents in the ortho-position to the two Oatoms of the four resorcinol moieties, in the kite-conformation (Fig. 5).