Crowned Ionic Liquids for Biomolecular Interaction Analysis.

On the basis of affinity recognition with positively charged side chains in peptides and proteins, a series of crowned 1,2,3-triazolium ionic liquids (CIL 1-6) was developed and found to be capable of quantitatively extracting peptides and proteins from the aqueous layer into the ionic liquid phase. All of the synthesized CIL 1-6 are liquid at room temperature. This is the first example of biomolecular recognition of both lysine- and arginine-containing peptides and proteins by CILs in pure ionic liquid phase.

Exploring silver ionic liquids for reaction-based gas sensing on a quartz crystal microbalance.

Reaction-based, sensitive sensing of aldehyde and ketone gases in real time was effectively achieved on QCM chips thin-coated with silver ionic liquids and , respectively. The method platform developed in this work involves straightforward synthesis of functional silver ionic liquids in water, and is label-free and highly chemoselective with superior gas reactivity for and and, most significantly, totally insensitive to moisture.

Reaction-based azide gas sensing with tailored ionic liquids measured by quartz crystal microbalance.

On the basis of the strain-promoted [3 + 2] cycloaddition reaction performed at ambient temperature, a label-free, online, and chemospecific gas-phase measurement of organic azides in real time was efficiently achieved on QCM chips thin-coated with tailored ionic liquid TIL 1.

Sensing ionic liquids for chemoselective detection of acyclic and cyclic ketone gases.

Based on specific chemical reactions carried out at ambient temperature, an ultrasensitive and chemoselective measurement of both acyclic and cyclic ketone gases, such as acetone (a disease biomarker) and cyclohexanone (a signature chemical emanating from C-4 plastic explosives), in real time was efficiently achieved on QCM chips thin-coated with sensing ionic liquids.

Ionic liquids promote PCR amplification of DNA.

A bicyclic imidazolium ionic liquid (4d), [b-4C-im][Br], was found to be highly effective not only for promoting PCR of GC-rich DNA by minimizing non-specific amplification, but also for facilitating PCR of normal-GC DNA under mild conditions.

Bicyclic 1,2,3-triazolium ionic liquids: synthesis, characterization, and application to rutaecarpine synthesis.

Starting with commercial reagents, bicyclic 1,2,3-triazolium ionic liquids [b-3C-tr][NTf(2)] (1) and [b-4C-tr][NTf(2)] (2) were synthesized in four steps with high overall isolated yields of 68% and 76%, respectively. Since the C-5 hydrogen is acidic, under basic condition ionic liquids 1 and 2 were readily methylated with methyl iodide to afford chemically stable ionic liquids 7 and 8 at room temperature (88% and 82%, respectively). Ionic liquid 1 was used as the ionic solvent to demonstrate its usefulness for the synthesis of rutaecarpine, a natural product.

Transimination reactions in [b-3C-im][NTf2] ionic liquid.

Compared to conventional molecular solvents, the ionic liquid [b-3C-im][NTf(2)] was found to promote transimination reactions with up to ∼100-fold rate enhancement. This rate effect observed at ambient temperature might be explained by the fact that the ionic liquid displays weak Lewis acidity with very low, if any, nucleophilicity and its imidazolium cation is expected to interact by associating with, and thus electrophilically activating, the C=N bond of the starting imine, leading to increased stabilization of the polar, charged intermediate species and ultimately, rapid product formation. Moreover, the presence of 1 mol% Sc(OTf)(3) in [b-3C-im][NTf(2)] further facilitates the transimination reactions studied.

One-pot synthesis of luotonin A and its analogues.

Starting with inexpensive reagents, a self-directed chemical process with the aid of a single metal triflate was readily achieved to concomitantly construct quinazoline and pyrroloquinoline cores to afford the synthesis of luotonin A and its analogues. Among all compounds prepared, 2c, 2d, and 3b exhibit more potent inhibitory activity than luotonin A against human topoisomerase I.

Chemoselective gas sensing ionic liquids.

Based on specific chemical reactions, chemoselective gas detection of aldehydes, ketones and amines in real time was efficiently achieved on QCM chips thin-coated with sensing ionic liquids (SILs).

Total synthesis of asperlicin C, circumdatin F, demethylbenzomalvin A, demethoxycircumdatin H, sclerotigenin, and other fused quinazolinones.

Using scandium triflate and microwaves, the direct double dehydrocyclization of anthranilate-containing tripeptides was achieved, affording the total syntheses of (i) quinazolino[3,2-a]benzodiazepinediones (), (ii) diazepino[2,1-b]quinazolinediones (), and (iii) pyrazino[2,1-b]quinazolinediones () with good overall isolated yields (23-43%, 37-47% and 31-56%, respectively). Among the quinazolino[3,2-a]benzodiazepinediones synthesized, (sclerotigenin), (circumdatin F), and (asperlicin C) are natural products.

Affinity ionic liquid.

An affinity ionic liquid, based on biomolecular recognition, was developed and found to be capable of quantitative partitioning of biomacromolecules from aqueous buffer to ionic liquid.

On the chemical stabilities of ionic liquids.

Ionic liquids are novel solvents of interest as greener alternatives to conventional organic solvents aimed at facilitating sustainable chemistry. As a consequence of their unusual physical properties, reusability, and eco-friendly nature, ionic liquids have attracted the attention of organic chemists. Numerous reports have revealed that many catalysts and reagents were supported in the ionic liquid phase, resulting in enhanced reactivity and selectivity in various important reaction transformations. However, synthetic chemists cannot ignore the stability data and intermolecular interactions, or even reactions that are directly applicable to organic reactions in ionic liquids. It is becoming evident from the increasing number of reports on use of ionic liquids as solvents, catalysts, and reagents in organic synthesis that they are not totally inert under many reaction conditions. While in some cases, their unexpected reactivity has proven fortuitously advantageous in others is has been a problem, it is imperative that when selecting an ionic liquid for a particular synthetic application, attention be paid to its compatibility with the reaction conditions. Even though, more than 200 room temperature ionic liquids are known, only a few reports have commented their effects on reaction mechanisms or rate/stability. Therefore, rather than attempting to give a comprehensive overview of ionic liquid chemistry, this review focuses on the non-innocent nature of ionic liquids, with a decided emphasis to clearly illuminate the ability of ionic liquids to affect the mechanistic aspects of some organic reactions thereby affecting and promoting the yield and selectivity.

Tin triflate-mediated total synthesis of circumdatin F, sclerotigenin, asperlicin C, and other quinazolino[3,2-a][1,4]benzodiazepines.

Using tin triflate, as an effective Lewis acid, and microwaves, direct double cyclizations of bis(anthranilate)-containing tripeptide precursors to afford the total syntheses of 7-substituted quinazolino[3,2-a][1,4]benzodiazepinediones (1a-f), including natural products circumdatin F (1a), sclerotigenin (1b), and asperlicin C (1c), were achieved with good overall isolated yields (23-62%).

Quantitative measurements of vancomycin binding to self-assembled peptide monolayers on chips by quartz crystal microbalance.

This paper describes direct binding of a small vancomycin to peptide ligands immobilized on a sensor chip using quartz crystal microbalance. In this study, the binding ligands were composed of three components: a molecular recognition element (peptide), a conformationally flexible and hydrophilic linker, and a long-chain alkanethiol. These peptide ligands were used to establish the well-packed, self-assembled monolayers on quartz chips and could be readily synthesized using conventional organic chemistry protocols. Results of quartz crystal microbalance measurements showed that vancomycin specifically associated with the d-Ala-d-Ala-containing peptide with an affinity of 3.2+/-0.3 microM and was, as expected, completely inactive to the self-assembled monolayer presenting l-Ala-l-Ala peptide. The dissociation constant obtained correlated well with values reported in literature and was further confirmed by surface plasmon resonance measurement (2.7+/-0.7 microM). The technique used in this study should be applicable to both peptidyl and nonpeptidyl ligands of greater complexity than that used here. This method is practical, it provides quantitative binding information, and complicated analysis is avoided.

Identification of a new chromophoric substrate in the library of amino acid p-nitroanilides for continuous assay of VanX, a D,D-dipeptidase essential for vancomycin resistance.

As one of key bacterial proteins involved in vancomycin resistance, VanX is a D,D-dipeptidase that impedes bacterial cell wall biosynthesis by hydrolyzing the essential D-Ala-D-Ala dipeptide. Based on a report by Crowder and co-workers that L-alanine-p-nitroanilide (L-Ala-pNA) was a useful substrate for continuous assay of VanX, we constructed a library of 35 L- and D-amino acid p-nitroanilides to provide the needed diversity to discover new substrates that are more specific than L-Ala-pNA. We report here that, among all compounds tested, D-leucine-p-nitroanilide (D-Leu-pNA) was found to be the best substrate for VanX enzyme (KM=8.9+/-1.2 mM, kcat=0.0102+/-0.0016 s(-1), kcat/KM=0.0012 mM(-1)s(-1)). Although it is catalytically inefficient, this new VanX substrate needs essentially no sophisticated synthetic chemistry for preparation and therefore offers a convenient means for routine analysis of enzyme catalysis and the screening of potential inhibitors. Moreover, because it is the uncommon leucine in its D form in D-Leu-pNA, enzymatic activities due to other contaminated species in Escherichia coli used for VanX overproduction should be greatly reduced.

Using surface plasmon resonance to directly identify molecules in a tripeptide library that bind tightly to a vancomycin chip.

This paper describes a procedure, based on direct binding, for identifying tight-binding ligands for a receptor immobilized on a sensor chip from an array of equimolar tripeptides using surface plasmon resonance. Vancomycin and a library of 96 tripeptides, with molecular weight ranging from 316 to 560 Da, were used as a model system to illustrate the procedure. A consensus structure of the strongest interacting peptides consisted of D-Ala at the C terminus and aromatic amino acid in the penultimate position. Ligands having this structure bound more tightly to vancomycin than the known D-Ala-D-Ala peptide. The throughput of our continuous assay is 96 compounds in 3.3 h, and the sample consumption is less than 2 microg per peptide and 1 ng for vancomycin. This procedure should be applicable to peptide libraries of greater complexity than that used here and to mixtures of small organic compounds.