Organic Chemistry of Nucleic Acids, Softcover reprint of the original 1st ed. 1971
Part A

The study of nucleic acids is one of the most rapidly developing fields in modern science. The exceptionally important role of the nucleic acids as a key to the understanding of the nature of life is reflected in the enormous number of published works on the subject, including many outstanding monographs and surveys. The pathways of syn­ thesis and metabolism of nucleic acids and the many and varied biological functions of these biopolymers are examined with the utmost detail in the literature. Nearly as much attention has been paid to the macromolecular chemistry of the nucleic acids: elucidation of the size and shape of their molecules, the study of the physicochemical properties of their solutions, and the appropriate methods to be used in such research. The surveys of the chemistry of nucleic acids which have been published so far deal almost entirely with their synthesis and, in particular, with the synthetic chemistry of monomers (nucleosides and nucleotides); less attention has been paid to the synthesis of poly­ nucleotides. There is yet another highly important aspect of the chemistry of nucleic acids which is still in the formative stage, the study of the reactivity of nucleic acid macromolecules and their components. This can make an important contribution to the deter­ mination of the structure of these remarkable biopolymers and to the correct 'understanding of their biological functions.

1 Structure of the Nucleic Acids.- I. Introduction.- II. Methods used to isolate DNA and to determine its properties. The principal types of DNA.- III. Methods used to isolate RNA and to determine its properties. The principal types of RNA.- IV. Structure of the polynucleotide chain.- V. Terminal groups of the polynucleotide chain.- VI. Structure of nucleoside components of nucleic acids.- 1. Major components of RNA.- 2. Minor components of RNA.- 3. Major components of DNA.- 4. Minor components of DNA.- VII. Nucleotide composition and the determination of identical nucleotide sequences in polynucleotides.- VIII. Sequence of nucleotides in the polynucleotide chain.- 1. Partial cleavage of polynucleotides.- 2. Principles of the unit method.- 3. Investigation of the primary structure of polynucleotides.- IX. Synthetic polynucleotides.- 1. Chemical methods of synthesis.- 2. Principles of enzymic synthesis of oligonucleotides and polynucleotides.- 2 Conformation of Nucleosides and Nucleosides.- I. Introduction.- II. Conformation of the components of nucleic acids.- 1. Conformation of heterocyclic rings.- 2. Conformation of carbohydrate residues.- 5. Mutual arrangement of the carbohydrate residues and heterocyclic rings.- 4. Intramolecular interactions.- 3 Electronic Structure and Reactivity of the Monomer Components of Nucleic acids.- I. Introduction.- II. Distribution of electron density in the heterocyclic bases of nucleic acids.- 1. Theoretical considerations.- 2. Experimental data and their comparison with calculated data.- III. Energetic characteristics of the bases of nucleic acids.- 1. Resonance energy.- 2. Energy of the highest filled and lowest empty orbitals.- IV. Tautomerism of the bases of nucleic acids.- 1. Theoretical considerations.- 2. Experimental data.- V. Ionization constants of the bases of nucleic acids.- 1. General considerations.- 2. Localization of the attachment and detachment of protons in nucleosides and nucleotides.- 3. Localization of charges in the ions of bases.- 4. Effect of different factors on the acid-base balance of the bases.- VI. General matters concerned with reactivity of the bases of nucleic acids.- 1. The use of quantum chemical calculations.- 2. The use of correlation equations.- 4 The Secondary Structure of Nucleic Acids.- I. Introduction.- II. General aspects of interaction between the bases of nucleic acids.- 1. Pairing of complementary bases.- III. Characteristics of interaction between the bases of nucleic acids and their derivatives in aqueous solutions.- 1. Association and self-association of bases, nucleosides, and nucleotides.- 2. Thermodynamic self-association constants of purine and pyrimidine derivatives.- 3. Concentration changes in optical properties of solutions of monomer components of nucleic acids.- 4. Concentration changes in NMR spectra of solutions of bases and nucleosides.- 5. Changes in the properties of bases when incorporated in oligonucleotides by comparison with monomers.- 6. Thermodynamic characteristics of interaction between bases and dinucleoside phosphates.- 7. Nature of the forces stabilizing associations of bases in aqueous solution.- IV. Investigation of the macrostructure of double-stranded DNA.- 1. The Watson and Crick hypothesis.- 2. Secondary and higher structures of circular DNAs.- V. Investigation of the secondary structure of double-stranded RNAs.- VI. Destruction of the macromolecular structure of double-helical molecules (denaturation).- 1. Factors influencing thermal denaturation.- 2. Special features of the denaturation of circular DNAs.- VII. Processes leading to restoration of the double-helical structure (renaturation).- 1. Factors influencing the renaturation process.- 2. Intramolecular interactions in DNA.- VIII. Single-stranded polynucleotides.- 1. The secondary structure of tRNA.- 2. The tertiary structure of tRNA.- 3. The secondary and tertiary structures of 5S RNA..- 5 Substitutions and Additions in the Heterocyclic Rings of the Bases of Nucleic Acids and their Derivatives.- I. Introduction.- II. Substitution and addition reactions at carbon atoms.- 1. Halogenation.- 2. Nitration.- 3. Hydroxymethylation, aminomethylation, and chloromethylation.- 4. Reactions with diazonium salts.- 5. Reactions with N-arylhydroxylamines and their derivatives.- 6. Isotopic exchange of hydrogen atoms.- 7. Addition reactions at the C5–C6 double bond of pyrimidine derivatives.- 8. Reduction.- 9. Reactions with nucleophilic reagents without rupture of the ring.- III. Substitutions and additions reaction at the nitrogen atoms.- 1. Interaction with alkylating agents.- 2. Interaction with reagents containing polarized C=C bonds.- 3. Interaction with reagents containing C=N bonds.- 4. Interaction with reagents containing C=O groups.- 5. Oxidation by peroxides.- 6 Reactions of Exocyclic Substituents of the Bases of Nucleic Acids and their Derivatives.- I. Introduction.- II. Substitution reactions at the nitrogen atom of an exocyclic amino group.- 1. N-Acylation.- 2. Reaction with aldehydes.- 3. Reaction with nitrous acid.- 4. Other substitutions in the amino group.- III. Substitutions at exocyclic oxygen and sulphur atoms.- 1. O-alkylation and the formation of cyclonucleosides..- 2. S-alkylation of thiopyrimidine derivatives.- 3. Oxidation of thiopyrimidine derivatives.- 7 Reactions Involving the Cleavage or Regrouping of Heterocyclic Rings of the Bases of Nucleic acids and their Derivatives.- I. Introduction.- II. Reactions of cleavage and rearrangement of the rings by the action of nucleophilic agents.- 1. Cleavage of the imidazole ring in purine derivatives.- 2. Cleavage of the pyrimidine ring in purine derivatives.- 3. Rearrangement of 1-N-alkyladenine derivatives into 6-exo-N-alkyl compounds.- 4. Opening and rearrangement of the ring in pyrimidine derivatives.- III. Cleavage by the action of hydrazine.- IV. Cleavage by the action of hydroxylamine.- V. Cleavage of rings by the action of potassium permanganate and osmium tetroxide.- VI. Cleavage by the action of peroxide derivatives.- 8 Hydrolysis of N-Glycosidic Bonds in Nucleosides, Nucleotides and their Derivatives.- I. Introduction.- II. Hydrolysis of N-glycosidic bonds catalyzed by acids.- 1. Effect of structural factors on the kinetics of hydrolysis of pyrimidine derivatives.- 2. Effect of structural factors on the kinetics of hydrolysis of purine derivatives.- 3. Acid hydrolysis of N-glycoside bonds in poly-nucleotides.- III. Hydrolysis of N-glycosidic bonds in pyrimidine deoxyribonucleosides, not catalyzed by acids or bases.- IV. Hydrolysis of N-glycosidic bonds in an alkaline medium.- V. Other reactions leading to cleavage of glycosidic bonds.- 9 Reactions of the Carbohydrate Residues of Nucleic Acids.- I. Introduction.- II. Acylation of hydroxyl groups of carbohydrate residues.- 1. Acylation.- 2. Aminoacylation.- 3. Preparation of esters with inorganic acids.- III. Alkylation of the hydroxyl groups of carbohydrate residues.- 1. Reaction with diazomethane.- 2. Reaction with alkyl halides.- 3. Reaction with triarylchloromethanes.- IV. Reactions of hydroxyl groups of carbohydrate residues with vinyl esters.- V. Reactions of hydroxyl groups of carbohydrate residues with carbonyl compounds and with their derivatives.- VI. Oxidation of carbohydrate residues.- 1. Oxidation of an isolated hydroxyl group.- 2. Oxidation of the cis-glycol group in ribo-derivatives.- 10 Cleavage of Phosphoester Bonds and some other Reactions of Phophate Groups of Nucleic Acids and their Derivatives.- I. Introduction.- II. Reactions with cleavage of P—O bonds.- 1. Hydrolysis of phosphomonoester bonds in ribonucleotides and degradation of RNA to nucleosides.- 2. Hydrolysis of phosphoester bonds in ribonucleoside cyclic phosphates.- 3. Hydrolysis of phosphodiester bonds in polynucleotides.- III. Reactions with rupture of C—O bonds.- 1. Cleavage of phosphoester bonds after removal of the heterocyclic bases.- 2. Cleavage of phosphoester bonds in terminal components of polynucleotides.- 3. Some other reactions of nucleic acids leading to the rupture of phosphodiester bonds.- IV. Reactions leading to the formation of phosphoester bonds.- 1. Alkylation at the phosphate group.- 2. Reactions of terminal phosphate groups in polynucleotides.- 11 Some Reactions of Minor Components of Nucleic Acids.- I. Introduction.- II. Reactions of 6-exo-N-isopentenyladenosine and its derivatives.- III. Reactions of pseudouridine and its derivatives.- IV. Reactions of 5-hydroxymethylpyrimidine derivatives.- 12 Photochemistry of the Nucleic Acids and their Components.- I Introduction.- II The basic concepts and laws of photochemistry.- III Absorption spectra of nucleic acids and their components.- IV Excited states of nucleic acids and their components.- 1 Characteristics of excited states.- 2. Electronic structure of bases of the nucleic acids in excited states.- V. Photochemical conversions of nucleic acids and their components.- 1. Photochemical reactions of pyrimidine derivatives.- 2. Photochemical reactions of purine derivatives.- VI. Photosensitized reactions.- VII. The photodynamic effect.- VIII. The action of visible light in the presence of iron ions.- IX. Photochemical reactions induced by excitation of a reagent.- X. Effect of chelating agents on photodimerization.- Index for Parts A and B.