Russell J. Perkins

Interaction of L-Phenylalanine with a Phospholipid Monolayer at the Water-Air Interface.

The interaction of L-phenylalanine with a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer at the air-water interface was explored using a combination of experimental techniques and molecular dynamics (MD) simulations. By means of Langmuir trough methods and Brewster angle microscopy, L-phenylalanine was shown to significantly alter the interfacial tension and the surface domain morphology of the DPPC film. In addition, confocal microscopy was used to explore the aggregation state of L-phenylalanine in the bulk aqueous phase. Finally, MD simulations were performed to gain molecular-level information on the interactions of L-phenylalanine and DPPC at the interface. Taken together, these results show that L-phenylalanine intercalates into a DPPC film at the air-water interface, thereby affecting the surface tension, phase morphology, and ordering of the DPPC film. The results are discussed in the context of biological systems and the mechanism of diseases such as phenylketonuria.

Chemical Equilibria and Kinetics in Aqueous Solutions of Zymonic Acid

The chemistry of pyruvic acid is of great interest due to its essential role in metabolism for all life and its role in atmospheric chemistry. Pyruvic acid under a wide range of conditions, including normal storage conditions, will spontaneously dimerize to form zymonic acid. We isolated zymonic acid and, using a variety of 1D and 2D NMR techniques, identified it as a single structure as a solid or dissolved in DMSO. When in aqueous solution, however, we identified a mixture of five different tautomers and hydrates in equilibrium with each other with no single dominant form. The kinetics of this conversion were studied in situ via NMR. The reactivity of the tautomers and hydrates in aqueous solution is investigated and discussed in terms of aqueous reaction mechanisms. There is strong evidence for a direct, reversible conversion from an enol to a geminal diol without passing through a ketone intermediate, which implies the reversible addition of water across a double bond under ambient conditions. Additionally, there is evidence for a base catalyzed lactone ring formation, which is in essence a base catalyzed esterification reaction. The equilibrium between pyruvic acid and its oligomers in aqueous solution is of consequence in the natural environment.

Mechanistic Description of Photochemical Oligomer Formation from Aqueous Pyruvic Acid

The aqueous phase photochemistry of pyruvic acid, an important oxidation product of isoprene, is known to generate larger oligomeric species that may contribute to the formation of secondary organic aerosol in the atmosphere. Using high resolution negative mode electrospray ionization mass spectrometry, the aqueous photochemistry of dilute solutions of pyruvic acid (10, 1, and 0.5 mM) under anaerobic conditions was investigated. Even at the lowest concentration, covalently bonded dimers and trimers of pyruvic acid were observed as photochemical products. We calculate that it is energetically possible to photochemically generate parapyruvic acid, a dimer of pyruvic acid that is known to form via dark oligomerization processes. Subsequent photochemical reactions of parapyruvic acid with pyruvic acid form larger oligomeric products, such as 2,4-dihydroxy-2-methyl-5-oxohexanoic acid. A robust and relatively simple photochemical mechanism is discussed that explains both the conditional dependence and wide array of products that are observed.

The Partitioning of Small Aromatic Molecules to Air–Water and Phospholipid Interfaces Mediated by Non-Hydrophobic Interactions

Phenylalanine has an important role both in normal biological function and in disease states such as phenylketonuria (PKU) and amyloid fibril diseases. Two crucial aspects of phenylalanine behavior in biological systems are its preferential partitioning into membranes and its propensity to cluster. In order to examine the intermolecular interactions that give rise to this behavior, the surface partitioning behavior was investigated for a series of molecules structurally related to phenylalanine (phenylglycine, phenylacetic acid, and tyrosine) both experimentally and by molecular dynamics simulations. Surface tension measurements were performed over time for aromatic solutions both in the presence and in the absence of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayer films, which functioned as simple model membranes. The observed trends in surface activity defy simple predictions based on solubility and hydrophobicity. The possibility of clustering is investigated through a combination of Langmuir trough, nuclear magnetic resonance (NMR), fluorescence self-quenching, and mass spectroscopy measurements. It is concluded that clustering does not occur in solution to a significant extent for these molecules, but interfacial clustering is likely. An explanation for observed trends in surface activity is presented on the basis of cluster stability and molecular conformational flexibility.

Photochemical Synthesis of Oligomeric Amphiphiles from Alkyl Oxoacids in Aqueous Environments

The aqueous phase photochemistry of a series of amphiphilic α-keto acids with differing linear alkyl chain lengths was investigated, demonstrating the ability of sunlight-initiated reactions to build molecular complexity under environmentally relevant conditions. We show that the photochemical reaction mechanisms for α-keto acids in aqueous solution are robust and generalizable across alkyl chain lengths. The organic radicals generated during photolysis are indiscriminate, leading to a large mixture of photoproducts that are observed using high-resolution electrospray ionization mass spectrometry, but these products are identifiable following literature photochemical mechanisms. The alkyl oxoacids under study here can undergo a Norrish Type II reaction to generate pyruvic acid, increasing the diversity of observed photoproducts. The major products of this photochemistry are covalently bonded dimers and trimers of the starting oxoacids, many of which are multi-tailed lipids. The properties of these oligomers are discussed, including their spontaneous self-assembly into aggregates.

Phenylalanine Increases Membrane Permeability

Biological membranes are a crucial aspect of living systems, controlling the organization and distribution of different chemical components. Control of membrane permeability is especially important for processes such as electron transport in metabolism and signal propagation in nerve cells. In this work, we show that the amino acid phenylalanine produces increased membrane permeability, which is likely responsible for some of the deleterious symptoms associated with high biological phenylalanine concentrations that occur with the genetic disorder phenylketonuria.

pH Dependence of the Aqueous Photochemistry of α-Keto Acids

α-Keto acids are important, atmospherically relevant species, and their photochemistry has been considered in the formation and processing of aerosols. Despite their atmospheric relevance, the photochemistry of these species has primarily been studied under extremely low pH conditions. Using a variety of analytical techniques, we characterize the extent of hydration and deprotonation for solutions of two α-keto acids, pyruvic acid and 2-oxooctanoic acid, as a function of pH. We find that changes in the initial solution composition govern the accessibility of different photochemical pathways, resulting in slowed photolysis under high pH conditions and a shift in photoproducts that can be predicted mechanistically.

Environmental processing of lipids driven by aqueous photochemistry of α-Keto acids

Sunlight can initiate photochemical reactions of organic molecules though direct photolysis, photosensitization, and indirect processes, often leading to complex radical chemistry that can increase molecular complexity in the environment. α-Keto acids act as photoinitiators for organic species that are not themselves photoactive. Here, we demonstrate this capability through the reaction of two α-keto acids, pyruvic acid and 2-oxooctanoic acid, with a series of fatty acids and fatty alcohols. We show for five different cases that a cross-product between the photoinitiated α-keto acid and non-photoactive species is formed during photolysis in aqueous solution. Fatty acids and alcohols are relatively unreactive species, which suggests that α-keto acids are able to act as radical initiators for many atmospherically relevant molecules found in the sea surface microlayer and on atmospheric aerosol particles.

Comment on “Reactivity of Ketyl and Acetyl Radicals from Direct Solar Actinic Photolysis of Aqueous Pyruvic Acid”

mechanism to explain the aqueous photolysis of pyruvic acid and its photoproducts. 1−12 The first steps of the mechanism are generally agreed upon: pyruvic acid absorbs a photon, undergoes intersystem crossing and internal con-version, and then initiates further chemistry from the T1 surface. From here, the mechanisms in the literature diverge. In 2006, Guzman ́et al. 6 suggested a mechanism that proceeds by proton-coupled electron transfer to explain two products: dimethyltartaric acid and an oxo-C7 species, for which two possible structures were provided. Griffith et al. 2 later presented a diff erent mechanism, in which hydrogen abstraction by triplet-state pyruvic acid initiates radical chemistry that yields dimethyltartaric acid and other observed products, 2,8,9 including acetoin and lactic acid. Griffith et al.’s identification of acetoin and lactic acid was based on three independent NMR techniques: gHMBCad ( 13 C− 1 H correlation), 1 H gCOSY ( 1 H− 1 H correlation), and DOSY (viscosity corrected diffusion constant data). 2 The high level of agreement in the results from these techniques between standards and post-photolysis solutions off ers irrefutable evidence that both acetoin and lactic acid are generated from the photolysis of aqueous pyruvic acid under certain conditions. Their identification was initially disputed by Eugene et al.; 3 however, Griffith et al. 4 addressed these concerns. In their recent publication, Eugene and Guzman ́ 1 claim to have