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Proton Magnetic Resonance Studies of Biologically Significant Molecules. I. Cation-Binding Properties of Nonactin. II. Salt Effects on Nucleotide Conformation


Prestegard, James Harold (1971) Proton Magnetic Resonance Studies of Biologically Significant Molecules. I. Cation-Binding Properties of Nonactin. II. Salt Effects on Nucleotide Conformation. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/G186-PD07.


Part I. Cation-Binding Properties of Nonactin.

In an effort to elucidate the cation specificity of certain macrocyclic antibiotics in metabolic behavior, the nature of the binding of K+, Na+ and Cs+ ions to the macrotetrolide nonactin and the molecular structure of the nonactin complexes have been investigated by 220 MHz proton magnetic resonance spectroscopy. Studies were made in dry acetone and in an acetone-water mixture as a function of varying perchlorate salt concentrations. Salt-induced chemical shifts were observed for all the nonactin protons, except H2 and H21, with accompanying changes in the vicinal coupling constants between the H2 and H3 protons and between the H5 and H6-H6, protons. Analysis of the salt-induced shifts yielded apparent formation constants for each of the ions in both solvent systems. The results indicate that all three ions bind to nonactin with equally high affinity in dry acetone, but that in wet acetone the binding constants are preferentially reduced making the potassium complex highly favored. It is shown that in wet acetone the alkali ion must be stripped of its hydration shell prior to its accomodation in the nonactin cavity j and hence we surmise that differences in hydration energies for the various ions must contribute significantly to the ion selective behavior of nonactin. Analysis of limiting chemical shifts and coupling constants also indicates that the nonactin mole­cule undergoes sizable conformation changes on complex formation, but that the complexes formed, all spherical with a nonsolvated ion at their center, differ little in exterior geometry. These results are interpreted in terms of their implications on a simple model for ion transport in a biological membrane.

Part II: Salt Effects on Nucleotide Conformation.

Aqueous solutions of uracil, uridine, deoxyuridine, uridine 3'-monophosphate (3'-UMP), and uridine 5'-monophos­phate (5'-UMP) have been investigated by proton magnetic resonance spectroscopy as a function of electrolyte concen­tration. The addition of a "solvent-structure breaking" salt such as Mg (ClO4)2 or NaClO4 to solutions of the nucleo­sides and nucleotides was found to result in significant upfield shifts of the uracil H6 resonance. In the cases of uridine and 5'-UMP, these salt-induced shifts were accom­panied by a decrease in the ribose H1,-H2, coupling constant, and in the case of 5'-UMP, significant changes in certain intramolecular nuclear Overhauser effects were observed. These observations are interpreted in terms of a salt­ induced conformation change, involving the orientation of the uracil base about the glycosidic bond and the puckering of the furanose ring. In view of apparent correlation be­tween the salt-induced shifts of the uracil H6 resonance and the "solvent-structure breaking" properties of the salt, it is proposed that the addition of salt modifies the sol­vent structure of the solution, which in turn can affect the average orientation of the base about the glycosidic bond. The ribose conformation change is considered to be a secondary effect resulting from nonbonded interactions be­tween the base and furanose moieties and occurring only to an extent commensurate with the rigidity of the ribose ring, Calculations based on current theories describing the roles of the solvent in hydrophobic bonding are given in support of these conclusions.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Chan, Sunney I.
Thesis Committee:
  • Unknown, Unknown
Defense Date:15 July 1970
Funding AgencyGrant Number
Record Number:CaltechTHESIS:04052018-112424721
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10793
Deposited By: Benjamin Perez
Deposited On:05 Apr 2018 21:06
Last Modified:21 Dec 2019 01:56

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