Mindy Levine

Amplification of enantiomeric concentrations under credible prebiotic conditions

Solutions with as little as 1% enantiomeric excess (ee) of d- or l-phenylalanine are amplified to 90% ee (a 95/5 ratio) by two successive evaporations to precipitate the racemate. Such a process on the prebiotic earth could lead to a mechanism by which meteoritic chiral α-alkyl amino acids could form solutions with high ee values that were needed for the beginning of biology.

Enantioselective Synthesis and Enantiomeric Amplification of Amino Acids under Prebiotic Conditions

A plausible origin of biomolecular homochirality is advanced, where alpha-methyl amino acids found on meteorites transfer their chirality in the synthesis of normal amino acids. This asymmetry can be amplified to nearly homochiral levels, thus providing the necessary prerequisite for life to start on this planet and elsewhere in the universe.

Imitating prebiotic homochirality on Earth.

We show how the amino acids needed on prebiotic earth in their homochiral L form can be produced by a reaction of L-alpha-methyl amino acids—that have been identified in the Murchison meteorite—with alpha-keto acids under credible prebiotic conditions. When they are simply heated together they perform a process of decarboxylative transamination but with almost no chiral transfer, and that in the wrong direction, producing D-amino acids from the L-alpha-methyl amino acids. With copper ion a square planar complex with two of the reaction intermediates is formed, and now there is the desired L to L transformation, producing small enantioexcesses of the normal L-amino acids. We also show how these can be amplified, not by making more of the L form but by increasing its concentration in water solution. The process can start with a miniscule excess and in one step generate water solutions with L/D ratios in the over 90% region. Kinetic processes can exceed the results from equilibria. We have also examined such amplifications with ribonucleosides, and have shown that initial modest excesses of the D-nucleosides can be amplified to afford water solutions with D to L ratios in the high 90’s. We have shown that the homochiral compound has two effects on the solubility of the racemate. On one hand it decreases the solubility of the racemate by its role in the solubility product, as a theoretical equation predicts. On the other hand, it increases the solubility of the racemate by changing the nature of the solvent, acting as a cosolvent with the water. This explains why the amplification, while large, is not as large as the simple theoretical equation predicts. Thus when credible examples are produced where small enantioexcesses of D-ribose are created under credible prebiotic conditions, the prerequisites for the RNA world will have been exemplified.

Cyclodextrin-Enhanced Extraction and Energy Transfer of Carcinogens in Complex Oil Environments

Reported herein is the use of γ-cyclodextrin for two tandem functions: (a) the extraction of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from oil samples into aqueous solution and (b) the promotion of highly efficient energy transfer from the newly extracted PAHs to a high-quantum-yield fluorophore. The extraction proceeded in moderate to good efficiencies, and the resulting cyclodextrin-promoted energy transfer led to a new, brightly fluorescent signal in aqueous solution. The resulting dual-function system (extraction followed by energy transfer) has significant relevance in the environmental detection and cleanup of oil-spill-related carcinogens.

Cyclodextrin-promoted energy transfer for broadly applicable small-molecule detection

Reported herein is the development of non-covalent, proximity-induced energy transfer from small-molecule toxicants to organic fluorophores bound in the cavity of γ-cyclodextrin. This energy transfer occurs with exceptional efficiency for a broad range of toxicants in complex biological media, and is largely independent of the spectral overlap between the donor and acceptor. This generally applicable phenomenon has significant potential in the development of new turn-on detection schemes.

Fluorescent detection of polycyclic aromatic hydrocarbons in ternary cyclodextrin complexes

Reported herein is a new method for the detection of polycyclic aromatic hydrocarbons (PAHs) which relies on energy transfer from the PAH to a near-infrared emitting squaraine fluorophore. This energy transfer occurs inside the γ-cyclodextrin cavity, with up to 35% emission observed from energy transfer compared with exciting the squaraine directly.

Water Exclusion and Enantioselectivity in Catalysis

Enzymes are large molecules. A number of arguments can be offered as to why this should be so, including the need for a large protein, consisting of a linear sequence of amino acids, to have a preferential folding into the biologically effective three-dimensional structure. There are also arguments that the dynamics of segment motion in a large protein can contribute to catalytic effectiveness. However, there is another argument for the large molecules characteristic of enzymes that is quite convincing—their size and structure let reactions occur inside a hydrophobic, nonaqueous, and nonpolar region of the protein while the outside of the protein has polar groups and is compatible with the aqueous solvents. Two interesting effects result from this. On the one hand, substrates that have hydrophobic groups will tend to bind in the nonpolar interior of the protein, where the catalytic groups can be located. On the other hand, water is in one respect an enemy of rate, even though the hydrophobic effect depends on water for its positive contribution to reaction rates. In a ACHTUNGTRENNUNGreaction in which acid and base groups play a catalytic role, water that is hydrogen bonded to these groups must normally be removed before they can effectively act on the substrate. The energy cost of desolvation of these catalytic groups—and perhaps also desolvation of the substrates—can slow the reaction considerably. For this reason it has often been proposed that the interior of the protein, without any water molecules or highly polar groups in it, is a better place to perform a catalyzed reaction and that such a medium will increase the rates of the processes.

Detection of Medium-Sized Polycyclic Aromatic Hydrocarbons via Fluorescence Energy Transfer

Reported herein is the use of proximity-induced non-covalent energy transfer for the detection of medium-sized polycyclic aromatic hydrocarbons (PAHs). This energy transfer occurs within the cavity of γ-cyclodextrin in various aqueous environments, including human plasma and coconut water. Highly efficient energy transfer was observed, and the efficiency of the energy transfer is independent of the concentration of γ-cyclodextrin used, demonstrating the importance of hydrophobic binding in facilitating such energy transfer. Low limits of detection were also observed for many of the PAHs investigated, which is promising for the development of fluorescence-based detection schemes.

Efficient extraction and detection of aromatic toxicants from crude oil and tar balls using multiple cyclodextrin derivatives

Herein we report the efficient extraction of aromatic analytes from crude oil and tar balls using multiple cyclodextrin derivatives. The known propensity of the cyclodextrins to bind hydrophobic guests in their hydrophobic interiors enhanced the extraction of aromatic analytes from the oil layer to the aqueous layer, with methyl-β-cyclodextrin and β-cyclodextrin providing the most significant enhancement in extraction efficiencies of aromatic toxicants (69% aromatic toxicants in aqueous layer in the presence of methyl-β-cyclodextrin compared to 47% in cyclodextrin-free solution for tar ball oil extraction), and provide optimal tunability for developing efficient extraction systems. The cyclodextrin derivatives also promoted efficient energy transfer in the aqueous solutions, with up to 86% efficient energy transfer observed in the presence of γ-cyclodextrin compared to 50% in the absence of cyclodextrin for oil spill oil extraction. Together, this dual function extraction followed by detection system has potential in the development of environmental remediation systems.

Sensitive and Selective Detection of Cesium via Fluorescence Quenching

Herein we report a robust and easy method for detecting cesium metal ion (Cs(+)) in partially aqueous solutions using the fluorescence quenching of 2,4-bis[4-(N,N-dihydroxyethylamino)phenyl]squaraine. This squaraine dye was found to be both highly sensitive (low limits of detection) and selective (limited response to other metals) for cesium ion detection. The detection is likely based on the metal complexing to the dihydroxyethanolamine moieties, which disrupts the donor-acceptor-donor architecture and leads to efficient quenching.