Biomaterial Database

A semi-empirical Hückel molecular orbital analysis of internucleotide phosphorothioate diesters. 1998

J K Weltman, and A S Karim

Department of Medicine, Brown University School of Medicine, Providence, RI 02912, USA.

Oligonucleotides that contain internucleotide phosphorothioate diesters have potential as anticancer therapeutic agents through sequence-specific antisense mechanisms. Although the chemical reactivity of internucleotide phosphorothioate diesters has been utilized to form phosphorothioate oligonucleotide conjugates, the theoretical basis for this chemical reactivity needs further elucidation. Calculations reported here, performed by the Huckel molecular orbital method, show that the energy of the highest occupied molecular orbital (HOMO) of the internucleotide phosphorothioate diester is 15.9 kcal/mole higher than that of the corresponding HOMO of the internucleotide phosphate diester. The electron density in the phosphorothioate HOMO is almost completely centered on the sulfur atom. The results of this parametricized Huckel molecular orbital analysis are consistent with the model of the internucleotide phosphorothioate sulfur as a soft nucleophile.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008968	Molecular Conformation	The characteristic three-dimensional shape of a molecule.	Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D002151	Calorimetry	The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D002627	Chemistry, Physical	The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.	Physical Chemistry,Chemistries, Physical,Physical Chemistries
D004583	Electrons	Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called CATHODE RAYS.	Fast Electrons,Negatrons,Positrons,Electron,Electron, Fast,Electrons, Fast,Fast Electron,Negatron,Positron
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D013873	Thionucleotides	Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D016376	Oligonucleotides, Antisense	Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.	Anti-Sense Oligonucleotide,Antisense Oligonucleotide,Antisense Oligonucleotides,Anti-Sense Oligonucleotides,Anti Sense Oligonucleotide,Anti Sense Oligonucleotides,Oligonucleotide, Anti-Sense,Oligonucleotide, Antisense,Oligonucleotides, Anti-Sense