Pyrimidine Nucleosides in Solution

Abstract

Proton magnetic resonance (PMR) spectra of 45 nucleoside and nucleotide derivatives of uracil, thymine, cytosine, 5-methylcytosine, and other substituted pyrimidines in water or dimethyl sulfoxide solutions have been analysed in order to correlate structure variations with molecular conformations and to gain insight into the nature of intramolecular forces which are responsible for the 'rigidity' of the molecules. Irrespective of thc structure of pyrimidine base and the absolute chemical shift values (6) the C(6)-H and, to a lesser degree, the C(5)-H and C(5)-CH3 resonances are shifted downfield by very similar amounts ( A S ) in the regular nucleosides or in the presence of charged or polar C-4' substituents. In detail, the following conformation-determining effects are seen.1. Ribose vs 2-deoxyribose substitution of a pyrimidine makes little difference for the chemical environment of base hydrogens but an intact pentofuranose ring (4'-0) and the exocyclic 5'-OH group are essential for a nucleoside to assume a specific conformation.2. Profound shielding or deshielding of H-6 by exocyclic nitrate, halogen, hydroxyl, phosphate, and carboxylate substituents indicates preference for the anti and gauche,gauche conformation ranges in all compounds except in the case of C-6 substitution.3. Halogen atoms and the hydroxyl group ( A 6 = 0.30 -0.40 ppm) interact with pyrimidine bases by induced polarisation of the C(5)=C(6) double bond, phosphate anions ( A 6 % 0.50 ppm) interact by the electrostatic attraction mechanism previously described, and in nucleoside 5'-carboxylates ( A 6 > 0.90 ppm) a hydrogen bond between -COO-and H-6 is formed.4. The deshielding effects caused by a 5'-OH group and monoanionic 5'-phosphate are similar ( A 6 % 0.35 -0.45 ppm), supporting the view that intramolecular rigidity of nucleosides and the nucleotide unit is not fundamentally different.This systematic survey, together with our previous studies of adenosine derivatives, provides a rationale for why the majority of both pyrimidine and purine nucleosides and nucleotides in solution exhibit closely comparable conformations, which in turn explain the group specificity of certain key enzymes in nucleic acid metabolism.Enzymes which act upon nucleosides or nucleotides usually show stringent specificities with respect to the conformation of the heterocyclic base, furanose moiety, and exocyclic hydroxyl or phosphate group of their substrates. For example, modified ribonucleotides in which the base deviates from a regular anti position are poor substrates of ribonucleases [l], RNA polymerase [2], or ribonucleotide reductase (H. Follmann and W. Ludwig, unpublished). 'H and13C nuclear magnetic resonance spectra are excellent tools to study This paper is part 3 of a series entitled Forces Stabilizing the Conformation of Nucleosides in Solution.Abbreviations. PMR, proton magnetic resonance. The IUPAC-IUB abbreviations are used for nucleic acid constituents. these three-dimensional structures in solutions, and in recent years have provided description...

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

“…Its structure is shown in Figure 8 (top, left); it is closely related to uridine (see Figure 1), but due to the (C6)-carboxylate group it exists in solution mainly in the syn conformation [89]. The (C6)COOH group is very acidic; for aqueous solution it was estimated that pK a = 0.5 ± 0.3 [92].…”

“…and/or U4S. Orotidine exists in solution mostly in the syn conformation [89]; for all the other nucleosides the anti conformation dominates. for the phosphate monoesters and from ref.…”

Complex Formation of Nickel(II) with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

“…In Figure 11 three more nucleotides are shown [142][143][144] for which stability constants of their Ni 2ϩ complexes have been measured. Orotidinate 5Ј-monophosphate (OMP 3Ϫ ) (Figure 11, top) is involved in the biosynthesis of pyrimidinenucleotides: OMP 3Ϫ is decarboxylated to UMP 2Ϫ (cf.…”

“…It must further be noted that in XMP the deprotonation of the xanthine moiety (pK a ϭ 5.30 ± 0.02) takes place [142,143], and fl avin mononucleotide (FMN 2Ϫ ϭ ribofl avin 5Ј-phosphate) as well as for comparison of glycerol 1-phosphate (G1P 2Ϫ ). OMP 3Ϫ is shown in its dominating syn conformation [144] and (XMP -H) 3Ϫ in its dominating anti conformation [48,63,107].…”

Pyridin-4-on-Nueleosid+: Stabilisierung der Struktur im Kristall und in wäßriger Lösung / Pyridine-4-on Nucleoside: Stabilisation of the Structure in the Crystal and in Aqueous Solution

“…Für diese bemerkenswerte Rigidität der Struktur in Lösung können sterische Effekte und polare Wechselwirkungen, vor allem aber die Zunahme der Wasserentropie bei dichter Packung aller Teile des gelösten Moleküls verantwortlich gemacht werden [2]. Es ist deshalb nicht verwunderlich, daß die gleiche Konformation auch mit modifizierten Basen im Kristall weitgehend beibehalten wird [3][4][5][6][7].…”