Wayne B. Bosma

DFT conformational studies of α‐maltotriose

Recent DFT optimization studies on α‐maltose improved our understanding of the preferred conformations of α‐maltose. The present study extends these studies to α‐maltotriose with three α‐D‐glucopyranose residues linked by two α‐[1→4] bridges, denoted herein as DP‐3s. Combinations of gg, gt, and tg hydroxymethyl groups are included for both “c” and “r” hydroxyl rotamers. When the hydroxymethyl groups are for example, gg‐gg‐gg, and the hydroxyl groups are rotated from all clockwise, “c”, to all counterclockwise, “r”, the minimum energy positions of the bridging dihedral angles (ϕH and ψH) move from the region of conformational space of (−, −), relative to (0°, 0°), to a new position defined by (+, +). Further, it was found previously that the relative energies of α‐maltose gg‐gg‐c and “r” conformations were very close to one another; however, the DP‐3s relative energies between hydroxyl “c” or “r” rotamers differ by more than one kcal/mol, in favor of the “c” form, even though the lowest energy DP‐3 conformations have glycosidic dihedral angles similar to those found in the α‐maltose study. Preliminary solvation studies using COSMO, a dielectric solvation method, point to important solvent contributions that reverse the energy profiles, showing an energy preference for the “r” forms. Only structures in which the rings are in the chair conformation are presented here.

Molecular dynamics simulations of structural transitions and phase coexistence in water pentamers

Molecular dynamics simulations of water pentamers were carried out using the semiempirical Parameterization Method 3 method to calculate the forces. Simulations were performed in the microcanonical ensemble, at several (average) vibrational temperatures. Three distinct transitions were observed in these systems, corresponding to the onset of phase coexistence and of two hydrogen bond rearrangements that were predicted by previous structural calculations. A detailed study of the high-temperature pentamer dynamics is presented, which clarifies the distinction between liquidlike behavior and simple structural rearrangements in these systems.

Investigation of the mechanism for the preparation of 6-phenyl-2,4-dioxotetrahydropyrans by the potassium carbonate promoted condensation between acetoacetate esters and benzaldehyde.

Treatment of benzaldehyde and an acetoacetate ester with potassium carbonate in an alcohol solvent proceeds via γ-C-alkylation rather than α-C-alkylation resulting in the formation of 6-phenyl-2,4-dioxotetrahydropyran. Based upon results from deuterium exchange experiments, carbon-13 labeling experiments, (1)H NMR monitoring studies, and reactivity studies, our proposed mechanism for this reaction involves deprotonation at the α-carbon, intramolecular proton transfer to form a γ-anion, addition of the resulting γ-anion to the carbonyl carbon of benzaldehyde, and intramolecular transesterification.

Assessment of the electronic structure and properties of trichothecene toxins using density functional theory

A comprehensive quantum chemical study was carried out on 35 type A and B trichothecenes and biosynthetic precursors, including selected derivatives of deoxynivalenol and T-2 toxin. Quantum chemical properties, Natural Bond Orbital (NBO) analysis, and molecular parameters were calculated on structures geometry optimized at the B3LYP/6-311+G** level. Type B trichothecenes possessed significantly larger electrophilicity index compared to the type A trichothecenes studied. Certain hydroxyl groups of deoxynivalenol, nivalenol, and T-2 toxin exhibited considerable rotation during molecular dynamics simulations (5 ps) at the B3LYP/6-31G** level in implicit aqueous solvent. Quantitative structure activity relationship (QSAR) models were developed to evaluate toxicity and detection using genetic algorithm, principal component, and multilinear analyses. The models suggest electronegativity and several 2-dimensional topological descriptors contain important information related to trichothecene cytotoxicity, phytotoxicity, immunochemical detection, and cross-reactivity.

Quantum chemical study of the structure and properties of citrinin

Detailed structures and electronic properties of three tautomeric forms of the toxin citrinin were investigated using several quantum calculation methods. Energetic preference of the predominant p- and o-quinone methide tautomeric forms is dependent on the method of calculation. A previously unstudied carboxylic acid enol tautomer was calculated to be surprisingly stable in vacuo, being within 2.5 kcal mol− 1 at the B3LYP/6-311++G(2d,2p) level of theory. Despite differences in bond nature and connectivity of tautomers, the natural bond orbital analysis revealed that tautomeric forms share similar natural charges and natural electron configurations. Calculated bond lengths corresponded with experimentally observed values and assignments for the calculated infrared vibrational frequencies are reported.

Determination of Citrinin Using Molecularly Imprinted Solid Phase Extraction Purification, HPLC Separation, and Fluorescence Detection

A liquid chromatography based method to detect citrinin in corn was developed using molecularly imprinted solid phase extraction (MISPE) sample clean-up. Molecularly imprinted polymers were synthesized using 1,4-dihydroxy-2-naphthoic acid as the template and an amine functional monomer. Density functional calculations suggest the mimic template interacts with the functional monomer in a similar manner as citrinin. Freundlich isotherm analysis indicated the template provided a significant imprinting effect for citrinin binding. A high performance liquid chromatography with fluorescence detection (HPLC-FD) method to detect citrinin in maize was developed utilizing the imprinted polymers for sample clean-up (excitation at 330 nm; emission at 500 nm). Recoveries of citrinin in spiked corn samples (0.03–3 µg g−1) were between 82.3–91.5%. This study demonstrates that molecularly imprinted polymers are applicable in the solid phase extraction clean-up of corn samples for citrinin determination by HPLC-FD.

Spectroscopic and time-dependent density functional investigation of the role of structure on the acid-base effects of citrinin detection

A time-dependent density functional theory (TD-DFT) study was carried out on tautomers of the mycotoxin citrinin in the neutral, anionic, and cationic forms to gain insight into the role of chemical structure on detection. Steady-state fluorescence studies of citrinin in micellar aqueous solutions produced unusual results for ionic surfactants and the neutral Triton X-100 enhanced fluorescence emission. Ground-state and time-dependent density functional studies were carried out on five tautomers of citrinin using the B3LYP density functional and the 6-311+G(2df,2p) basis set. The investigation revealed that deprotonation is a major factor governing the shifts in fluorescence excitation and emission maxima. Moreover, the position of the lowest unoccupied molecular orbitals is removed from the fluorophore moiety of citrinin in the dianionic state which is consistent with the diminished fluorescence of the toxin in basic solutions. The ionic characteristics of certain chemosensors can influence the structure and intrinsic spectroscopic properties of citrinin.

Infrared Spectroscopic Analysis of the Adsorption of Pyridine Carboxylic Acids on Colloidal Ceria

Surface adsorption of a homologous series of pyridine carboxylic acids on a hydrated colloidal cerium dioxide (ceria) film is characterized using the combination of experimental and computationally determined infrared (IR) spectra. Experimental analyses employ attenuated total reflectance (ATR) IR spectroscopy of deposited colloidal ceria thin films equilibrated with three pyridine carboxylic acids at pH 3.0, 5.5, and 8.5. The corresponding computational IR spectra for the energy-minimized intermediate and base forms of the pyridine carboxylic acids use density functional theory calculations at the B3LYP/6-311++G** level of theory. Solvent effects are modeled using both the COSMO implicit solvation model and the inclusion of explicit water molecules. Experimental IR spectra show that the adsorptive interactions between the pyridine carboxylic acids and ceria surface are due to the outer-sphere coordination of cerium ions in the films. Vibrational assignments based on combined experimental and computational results indicate that both pyridyl ring nitrogen and carboxylate functional groups account for the interaction of pyridine carboxylic acids at ceria surfaces. Experimentally determined Langmuir constants point to the intermediate form of picolinic acid (pyridine-2-carboxylic acid) as having the strongest adsorption to ceria compared to the other pyridine carboxylic acids investigated. The enhanced adsorption of picolinic acid is attributed to the adjacency of the protonated pyridyl nitrogen and the carboxylate group relative to nicotinic acid (pyridine-3-carboxylic acid) and isonicotinic acid (pyridine-4-carboxylic acid).

Chapter 6:Quantum Chemical Studies of Estrogenic Compounds

Nuclear receptors play an important role in the regulation of gene expression and gene function in animals through the direct interaction with DNA, especially during development and homeostasis maintenance.1 Activation of this class of receptors occurs through the molecular recognition with a broad ...