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Computational strategy for predicting the specific optical rotation values of large flexible molecules

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Item Summary

Title: Computational strategy for predicting the specific optical rotation values of large flexible molecules
Authors: Melnichuk, Anna
Keywords: Molecular rotation -- Data processing
Optical rotation -- Data processing
Issue Date: 2006
Abstract: The topic discussed in this thesis concerns the challenges faced when one needs to find a theoretical value for the specific optical rotation ([α]D) for a relatively large and flexible molecule. A method was developed to find all of the low-energy conformers that may be present in solution and to calculate the [α]D values for these conformers without exceeding a reasonable computer time. Initially, the effects of changes in molecular geometry on [α]D values were investigated using several small and rigid molecules. (2S)-2-methyl oxirane was used to investigate the effect of rotating the methyl group on calculated [α]D values. The [α]D values were calculated using different basis sets which were found to produce similar [α]D values at the optimized geometry. However, for a non-equilibrium geometry the different basis sets gave very different [α]D values. This variation was attributed to the diffuse p-orbital basis functions on hydrogen atoms which are present in the aug-cc-pVDZ basis set and absent in the 6-3IG* basis set. 2-Propanol was used to show that even though it is an achiral molecule and thus has an [α]D value of zero, there are several low-energy conformers of 2-propanol which have non-zero calculated [α]D values. The three low-energy conformers were obtained by rotating the hydroxy group about the HOCH dihedral angle: the trans conformer has C1 symmetry and an [α]D value of zero. However, the two gauche conformers have C, symmetry and a non-zero [α]D values which have the same magnitude but opposite sign. The calculated [α]D values for each conformer were averaged using Boltzmann statistics to produce an average [α]D value of zero. The Monte Carlo (Me) program was written to search for all of the low-energy conformers of flexible molecules by randomly varying user-specified dihedral angles along the molecular backbone. The MC program used AMI semiempirical method in the GAMESS software for fast energy screening. These AMI low-energy conformers found using the MC program were re-optimized at the B3LYP/6-310* level of theory and then their [α]D values were calculated at the B3LYP/aug-cc-pVDZ level of theory. The effectiveness of the MC program at correctly finding the low-energy conformers was tested using the achiral molecule: 3-hydroxypentadial. The average [α]D value for this molecule converged to zero after two MCruns. The magnitude of error for the calculated [α]D value when the MC routine was used to find the low-energy conformers was found to be ±40° based on six MC runs using a chiral molecule: (S)-(+)-ethyl 3-hydroxybutanoic acid with a known experimental [α]D value. The absolute stereochemistry of 3,5-dimethoxyoctan-1-ol with two chiral centers is currently unknown. However, the relative stereochemistry of the two chiral centers is known to be syn. After seven MC runs, the average [α]D value converged to 61° for an (R,R) conformer. The experimental [α]D value is still needed to evaluate whether if the calculated value is correct within the expected error of ±40° and to assign the absolute stereochemistry for 3,5-dimethoxyoctan-l-ol. Using the methods developed in this work, it appears feasible to compute the [α]D values for even larger flexible molecules with multiple chiral centers. This tactic will be very useful in cases where other methods for elucidating the absolute stereochemistry, such as NMR and X-ray diffraction, do not work well.
Description: Thesis (M.S.)--University of Hawaii at Manoa, 2006.
Includes bibliographical references.
xi, 133 leaves, bound ill. 29 cm
Rights: All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections:M.S. - Chemistry

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