The Copper(II)-Thiodiacetate (tda) Chelate as Efficient Receptor of N9-(2-Hydroxyethyl)Adenine (9heade): Synthesis, Molecular and Crystal Structures, Physical Properties and DFT Calculations of [Cu(tda)(9heade)(H2O)]·2H2O Rosales-Martínez, Carmen Matilla-Hernádez, Antonio Choquesillo Lazarte, Duane Niclos Gutiérrez, Juan Copper(II) Thiodiacetate chelate Synthetic adenine nucleoside Molecular and crystal structure Chelate-nucleoside recognition Water-mediated interligand interactions Physical properties DFT calculations This research was funded by MICIU/AEI of Spain project PID2020-115637GB-I00 FEDER, MICINN of Spain project PGC2018-102047-B-I00, Project B-FQM-478-UGR20 (FEDER-Universidad de Granada, Spain). Funds and instrumental support of research group FQM-283 (Junta de Andalucia, Spain) are also acknowledged. Supplementary Materials: The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/molecules28155830/s1 Considering that Cu(tda) chelate (tda: dithioacetate) is a receptor for adenine and related 6-aminopurines, this study reports on the synthesis, molecular and crystal structures, thermal stability, spectral properties and DFT calculations related to [Cu(tda)(9heade)(H2O)]& BULL;2H(2)O (1) [9heade: N9-(2-hydroxyethyl)adenine]. Concerning the molecular recognition of (metal chelate)-(adenine synthetic nucleoside), 1 represents an unprecedented metal binding pattern (MBP) for 9heade. However, unprecedentedly, the Cu(tda)-9heade molecular recognition in 1 is essentially featured in the Cu-N1(9heade) bond, without any N6-HMIDLINE HORIZONTAL ELLIPSISO(carboxyl tda) interligand interaction. Nevertheless, N1 being the most basic donor for N9-substituted adenines, this Cu-N1 bond is now assisted by an O2-water-mediated interaction (N6-HMIDLINE HORIZONTAL ELLIPSISO2 and O2MIDLINE HORIZONTAL ELLIPSISCu weak contact). Also, in the crystal packing, the O-H(ol) of 9heade interacts with its own adenine moiety as a result of an O3-water-mediated interaction (O(ol)-HMIDLINE HORIZONTAL ELLIPSISO3 plus O3-H36MIDLINE HORIZONTAL ELLIPSIS & pi;(adenine moiety)). Both water-mediated interactions seem to be responsible for serious alterations in the physical properties of crystalline or grounded samples. Density functional theory calculations were used to evaluate the interactions energetically. Moreover, the quantum theory of atoms-in-molecules (QTAIM), in combination with the noncovalent interaction plot (NCIPlot), was used to analyze the interactions and rationalize the existence and relative importance of hydrogen bonding, chalcogen bonding and & pi;-stacking interactions. The novelty of this work resides in the discovery of a novel binding mode for N9-(2-hydroxyethyl)adenine. Moreover, the investigation of the important role of water in the solid state of 1 is also relevant, along with the chalcogen bonding interactions demonstrated by the density functional theory (DFT) study. 2023-09-25T07:04:18Z 2023-09-25T07:04:18Z 2023-08-02 journal article Rosales-Martínez, C.; Matilla-Hernádez, A.; Choquesillo-Lazarte, D.; Frontera, A.; Castiñeiras, A.; Niclós-Gutiérrez, J. The Copper(II)-Thiodiacetate (tda) Chelate as Efficient Receptor of N9-(2-Hydroxyethyl)Adenine (9heade): Synthesis, Molecular and Crystal Structures, Physical Properties and DFT Calculations of [Cu(tda)(9heade)(H2O)]·2H2O. Molecules 2023, 28, 5830. [https://doi.org/10.3390/molecules28155830] https://hdl.handle.net/10481/84605 10.3390/molecules28155830 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI