Supramolecular Nature of Multicomponent Crystals Formed from 2,2'-Thiodiacetic Acid with 2,6-Diaminopurine or N9-(2-Hydroxyethyl)adenine.

The synthesis and characterization of the multicomponent crystals formed by 2,2'-thiodiacetic acid (H2tda) and 2,6-diaminopurine (Hdap) or N9-(2-hydroxyethyl)adenine (9heade) are detailed in this report. These crystals exist in a salt rather than a co-crystal form, as confirmed by single crystal X-ray diffractometry, which reflects their ionic nature. This analysis confirmed proton transfer from the 2,2'-thiodiacetic acid to the basic groups of the coformers. The new multicomponent crystals have molecular formulas [(H9heade+)(Htda-)] 1 and [(H2dap+)2(tda2-)]·2H2O 2. These were also characterized using FTIR, 1H and 13C NMR and mass spectroscopies, elemental analysis, and thermogravimetric/differential scanning calorimetry (TG/DSC) analyses. In the crystal packing the ions interact with each other via O-H⋯N, O-H⋯O, N-H⋯O, and N-H⋯N hydrogen bonds, generating cyclic hydrogen-bonded motifs with graph-set notation of R22(16), R22(10), R32(10), R33(10), R22(9), R32(8), and R42(8), to form different supramolecular homo- and hetero-synthons. In addition, in the crystal packing of 2, pairs of diaminopurinium ions display a strong anti-parallel π,π-stacking interaction, characterized by short inter-centroids and interplanar distances (3.39 and 3.24 Å, respectively) and a fairly tight angle (17.5°). These assemblies were further analyzed energetically using DFT calculations, MEP surface analysis, and QTAIM characterization.

Dicopper(II)-EDTA Chelate as a Bicephalic Receptor Model for a Synthetic Adenine Nucleoside.

In the extensive field of metal ions, their interactions with nucleic acids, and their constituents, the main aim of this work is to develop a metal chelate suitable to recognize two molecules of an adenine nucleoside. For this purpose, the dinuclear chelate Cu2 (µ-EDTA) (ethylenediaminetetraacetate(4-) ion (EDTA)) is chosen as a bicephalic receptor model for N9-(2-hydroxyethyl)adenine (9heade). A one-pot synthesis is reported to obtain the compound [Cu2(µ2-EDTA)(9heade)2(H2O)4]·3H2O, which has been characterized by single-crystal X-ray diffraction and various spectral, thermal, and magnetic methods. The complex unit is a centro-symmetric molecule, where each Cu (II) center is chelated by a half-EDTA, and is further surrounded by an N7-dentate 9heade nucleoside and two non-equivalent trans-O-aqua molecules. The metal chelate-nucleoside molecular recognition is referred to as an efficient cooperation between the Cu-N7(9heade) coordination bond and a (9heade)N6-H···O(carboxyl, EDTA) interligand interaction. Theoretical calculations are also made to account for the relevance of this interaction. The extreme weakness with which each water molecule binds to the metal center disturbs the thermal stability and the infrared (FT-IR) and electron spin resonance (ESR) spectra of the compound.

Molecular recognition modes between adenine or adeniniun(1+) ion and binary M(II)(pdc) chelates (MCoZn; pdc=pyridine-2,6-dicarboxylate(2-) ion).

Mixed ligand M(II)-complexes (MCoZn) with pyridine-2,6-dicarboxylate(2-) chelator (pdc) and adenine (Hade) have been synthesized and studied by X-ray diffraction and other spectral and thermal methods: [Cu(pdc)(H(N9)ade)(H2O)] (1), [Cu2(pdc)2(H2O)2(µ2-N3,N7-H(N9)ade)]·3H2O (2), trans-[M(pdc)(H(N9)ade)(H2O)2]·nH2O for MCo (3-L, 3-M, 3-H) or Zn (4-L, 4-H), where n is 0, 1 or 3 for the 'lowest' (L), 'medium' (M) and 'highest' (H) hydrated forms, and the salt trans-[Ni(pdc)(H2(N1,N9)ade)(H2O)2]Cl·2H2O (5). In all the nine compounds, both neutral and cationic adenine exist as their most stable tautomer and the molecular recognition pattern between the metal-pdc chelates and the adenine or adeninium(1+) ligands involves the MN7 bond in cooperation with an intra-molecular N6H⋯O(coordinated carboxylate) interligand interaction. In addition the dinuclear copper(II) compound (2) has the CuN3 bond and the N9H⋯O(coord. carboxylate) interaction. The structures of mononuclear ternary complexes proved that the molecular recognition pattern is the same irrespective of (a) the coordination geometry of the complex molecule, (b) the different hydrated forms of crystals with Co or Zn, and (c) the neutral of cationic form of the adenine ligand. These features are related to the mer-NO2 chelating ligand conformation (imposed by the planar rigidity of pdc) as a driving force for the observed metal binding mode.

Structural insights on the molecular recognition patterns between N(6)-substituted adenines and N-(aryl-methyl)iminodiacetate copper(II) chelates.

For a better understanding of the metal binding pattern of N(6)-substituted adenines, six novel ternary Cu(II) complexes have been structurally characterized by single crystal X-ray diffraction: [Cu(NBzIDA)(HCy5ade)(H2O)]·H2O (1), [Cu(NBzIDA)(HCy6ade)(H2O)]·H2O (2), [Cu(FurIDA)(HCy6ade)(H2O)]·H2O (3), [Cu(MEBIDA)(HBAP)(H2O)]·H2O (4), [Cu(FurIDA)(HBAP)]n (5) and {[Cu(NBzIDA)(HdimAP)]·H2O}n (6). In these compounds NBzIDA, FurIDA and MEBIDA are N-substituted iminodiacetates with a non-coordinating aryl-methyl pendant arm (benzyl in NBzIDA, p-tolyl in MEBIDA and furfuryl in FurIDA) whereas HBAP, HCy5ade, HCy6ade and HdimAP are N(6)-substituted adenine derivatives with a N-benzyl, N-cyclopentyl, N-cyclohexyl or two N-methyl groups, respectively. Regardless of the molecular (1-4) or polymeric (5-6) nature of the studied compounds, the Cu(II) centre exhibits a type 4+1 coordination where the tridentate IDA-like chelators adopt a mer-conformation. In 1-5 the N(6)-R-adenines use their most stable tautomer H(N9)adenine-like, and molecular recognition consists of the cooperation of the CuN3(purine) bond and the intra-molecular interligand N9H···O(coordinated carboxy) interaction. In contrast, N(6),N(6)-dimethyl-adenine shows the rare tautomer H(N3)dimAP in 6, so that the molecular recognition with the Cu(NBzIDA) chelate consist of the CuN9 bond and the N3H···O intra-molecular interligand interaction. Contrastingly to the cytokinin activity found in the free ligands HBAP (natural cytokinin), HCy5ade and HCy6ade, the corresponding Cu(II) ternary complexes did not show any activity.