Metal ion binding patterns of acyclovir: Molecular recognition between this antiviral agent and copper(II) chelates with iminodiacetate or glycylglycinate

Structural and Theoretical Evidence of the Depleted Proton Affinity of the N3-Atom in Acyclovir

“…The all-trans centrosymmetric anions (Figures 2 and A2) have symmetry-related pairs of O-aqua, N7-acv, and O-sulfate donor atoms featuring a rather typical elongated-octahedral Cu(II) coordination, type 4 + 2, with bond lengths of Cu-O(aqua) of 1.963(2) Å, of Cu-N7(acv) of 2.018(2) Å, and of Cu-O(sulfate) of 2.427(2) Å, respectively (Table A2). It seems clear that the, shortest strongly-bound Cu-O(aqua) favor the cooperation of each Cu-N7(acv) bond with an intra-molecular interligand (aqua)O1-H1B···O6(acv) interaction (2.615(3) Å, 157.3 • ) (Table A3), thus leading to the most common MBP of the acv ligand [2][3][4][5][6][7][8][9]12]. This fact imposes the coordination of O-sulfate atoms towards the apical/distal sites of the copper(II) surrounding.…”

“…This acyclic guanine nucleoside analog has proved to bind nucleoside phosphorylases [1] as well as several metal ions. Structural knowledge on mixed-ligand metal-acv complexes (see selected reference [2][3][4][5][6][7][8][9][10][11][12]) supports a variety of metal binding patterns (MBPs) and interesting molecular recognition features. So far, the reported MBPs can be summarized as follows: (a) the formation of the M-N7 bond, with [2][3][4][5][6][7][8][9]12] or without [8,10] the cooperation of an intra-molecular interligand A-H···O6(acv) interaction (A=O or N acceptor); (b) the N7,O6-chelation mode [11]; (c) the µ 2 -N7,O(ol) (see Figure 1) bridging role [3]; and finally, (d) a multi-functional role featured by the µ 3 -N7,O6,O(e)+O(ol), which comprises the bridging, chelating, and tetradentate modes of acv [12].…”

Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax) Using Density Functional Theory Methods

“…Thus, it is one of the tasks of the present manuscript. Conformations of some derivatives of ACV with biological activities have been reported [17], as well as studies of complexes of ACV with several metals [18,19]. …”

Highest Reported Denticity of a Synthetic Nucleoside in the Unprecedented Tetradentate Mode of Acyclovir

“…Metal-binding patterns (MBP) of acv are supported by crystal structures of mixed-ligand metal complexes. − They can be summarized as follows: MBP-1: M-N7 bond together with ,,,− ,− or without − ,,, an intramolecular interligand O–H···O6­(acv) or N–H···O6­(acv) interaction. MBP-2: Chelation-N7,O6. ,, MBP-3: μ 2 -N7,O″ bridging mode. , Both the highest denticity , and acv/M ratio ,,,,,,, are two.…”

“…Despite this fact, two stretching absorptions for the ν­(CO) of acv could be identified: a strong sharp band at 1683 cm –1 and a smooth shoulder near 1675 cm –1 , assigned to monodentate acv and μ 3 -acv. Related copper­(II) complexes having solvate and/or coordinated acv ligand also exhibit the ν­(CO) band at similar wavelenghth, which has been used with high diagnostic value. ,, In contrast, spectra recorded on various commercial samples of acv·0.66H 2 O show the corresponding ν­(CO) splitted in two partially overlapped bands at 1720 ± 3 and 1695 ± 2 cm –1 , which is not observed in the spectrum of 1 (see Supporting Information).…”