9-Ethyladenine: Mechanochemical Synthesis, Characterization, and DFT Calculations of Novel Cocrystals and Salts

Abstract

Liquid-assisted grinding and solvent crystallizations have been undertaken to prepare salts and cocrystals of the modified nucleobase 9-ethyladenine with several carboxylic acids. The new solid forms have been characterized by X-ray powder and single crystal diffraction, attenuated total reflectance Fourier transformed infrared spectroscopy and thermal methods. From single crystal structures we have observed that the length of the alkylic chain in the carboxylic acid prevents from a canonical self-assembly for the longest coformer. Moreover, density functional theory (DFT) calculations combined with

Oxalic Acid, a Versatile Coformer for Multicomponent Forms with 9-Ethyladenine

“…The individual dissociated energies shown in Figure 8 ). These values are comparable to previously reported energies for adenine cocrystals with several carboxylic acids [18]. The QTAIM analysis also reveals the existence of a much weaker H-bond established between the aromatic CH bond of the six membered In the literature, the ability of adenine derivatives and cocrystals to form R 2 2 (10) homodimers or a variety of heterodimers via the Hoogsteen face has been described and energetically evaluated using the QTAIM analysis [41][42][43].…”

“…9-Ethyladenine (9ETADE) is a modified nucleobase with the amino group at N(9) blocked by an ethyl chain (Scheme 1a). We have previously reported the ability of this modified nucleobase to form different salts and/or cocrystals with alkyl dicarboxylic acids (HOOC-Xn-COOH, with n from 1 to 4) as coformers depending on the ΔpKa [18]. Now, as a continuation of our work related to this modified purine, we describe herein the special situation with oxalic acid.…”

“…One of the main objectives of conducting salt/cocrystal screenings of active molecules is to find suitable candidates with the best physical-chemical properties. In a previous work, we described two new hydrated salts (malonate and fumarate) and an anhydrous succinate of 9ETADE [18]. Herein, the aqueous solubilities of 9-ethyladenine and the three anhydrous candidates (the two anhydrous oxalate salts prepared in this work and the succinate salt of 9ETADE) were determined for comparative purposes (Table 2).…”

“…The QTAIM analysis also reveals the existence of a much weaker H-bond established between the aromatic CH bond of the six membered In the literature, the ability of adenine derivatives and cocrystals to form R 2 2 (10) homodimers or a variety of heterodimers via the Hoogsteen face has been described and energetically evaluated using the QTAIM analysis [41][42][43]. For instance, the reported energies associated with NH•••N H-bonds in R 2 2 (10) ethyl-adenine homodimers in its co-crystals with malonic and fumaric acid are 3.6 and 4.0 kcal/mol [18], respectively. These values are comparable to those obtained for compound 1.…”

Novel Cd (II) Coordination Polymers Afforded with EDTA or Trans-1,2-Cdta Chelators and Imidazole, Adenine, or 9-(2-Hydroxyethyl) Adenine Coligands

“…A bond path and bond critical point (CP) interconnecting two atoms can be used as an unambiguous indication of interaction [26]. Moreover, this type of analysis has been recently used in similar systems [27][28][29][30][31]. The distribution of bond CPs and bond paths of the two motifs analyzed above are shown in Figure 14.…”