Rationalizing the Structural Variability of the Exocyclic Amino Groups in Nucleobases and Their Metal Complexes: Cytosine and Adenine

Abstract

The exocyclic amino groups of cytosine and adenine nucleobases are normally almost flat, with the N atoms essentially sp(2) hybridized and the lone pair largely delocalized into the heterocyclic rings. However, a change to marked pyramidality of the amino group (N then sp(3) hybridized, lone pair essentially localized at N) occurs during i) involvement of an amino proton in strong hydrogen bonding donor conditions or ii) with monofunctional metal coordination following removal of one of the two protons.

Multiple Condensation Reactions Involving PtII/PdII−OH2, Pt−NH3, and Cytosine−NH2 Groups: New Twists in Cisplatin−Nucleobase Chemistry

“…Consequently, the double‐bond character of the C4−N4 bond also increases, the bond length between C4−N4 shortens by 0.012–0.014 Å, which results in a value of 1.323 Å, significantly shorter than that expected for a single C−N bond. The computed values are similar to the experimental ones determined for similar (tmda)Pd 2+ complexes and for compound 3 (see Table ). Finally, inclusion of the closest nitrate groups in the simulation results in an increase of the planarity of the Pd‐N4‐C4‐N3‐Pt metallacycle (Table ).…”

“…Interestingly, five‐membered rings of analogous complexes enclosing a μ‐OH − bridge display a flat geometry . A remarkable aspect of this kind of metal complexes is the hybridization exhibited by the exocyclic amino groups of cytosine, which has been studied in detail, will be discussed later. The C4−N4 bond lengths (C4a−N4a, 1.333(11), C4b−N4b 1.330(12) Å) in both cations of compound 3 match that of 1‐methylcytosine (1.332(2) Å), which suggest a considerable double‐bond character.…”

The α-D-anomer of 2′-deoxycytidine: crystal structure, nucleoside conformation and Hirshfeld surface analysis

“…This suggests that the lone electron pair of the amino group is at least partially delocalized into the pyrimidine ring. These observations are consistent with earlier reports of 1-methylcytosine also reporting on the partial double-bond character of the amino group (Rossi & Kistenmacher, 1977;Fonseca Guerra et al, 2014).…”

Connectivity patterns and rotamer states of nucleobases determine acid–base properties of metalated purine quartets

“…Clearly, the N6H 2 group of adenine behaves largely as H bond donor to other nucleobases (e.g., WatsonCrick or Hoogsteen pairs with thymine) or another co-ligand, e.g., a water molecule in the coordination sphere of a metal ion bonded to the adenine [96]. Perhaps in special situations N6H 2 might act as a very weak H bond acceptor, as seen with N2H 2 of guanine occasionally [97][98][99], yet this is unlikely in the large majority of cases, as N6 is effectively sp 2 hybridized, with the lone electron pair from the N atom largely delocalized into the heteroaromatic ring [100]. For this very reason, deprotonation of the exocyclic amino group (to give the anion) or a shift of one of the two protons to another ring-N atom (hence to generate the rare imino tautomer) is required to make N6 a good H bond acceptor.…”