Polymeric (anion-π)_n interactions in crystals of 2-(2,4,6-trioxo-[1,3,5]triazinan-1-yl)ethylammonium iodide

Introduction

Cyanuric acid, that in gas phase, solution and solid phase exists as isocyanuric acid [1], [2] has long been considered as an important derivative of s-triazine, weakly aromatic [3], biodegradable and non toxic to human and aquatic animals [4]. Besides its widespread use in outdoor swimming pools [5] and large water systems [6] to protect chlorine breakdown from sunlight, cuanuric acid derivatives of ascorbic acid have been investigated as potential anticancer agents [7]. Moreover, cyanuric acid-based siderophore analogs able to bind ferric ion stoichiometrically (artificial iron chelators) [8] and β-lactam (lorabid) conjugates [9] were synthesized to provide new classes of antimicrobial agents and siderophore-mediated drug delivery systems.

Perhaps the most representative are the applications of cyanuric acid and its derivatives in the area of supramolecular chemistry [10]. Thus, Whitesides and co-workers designed and performed noncovalent syntheses of supramolecular aggregates of cyanuric acid and melamine derivatives (Figure 1, structure A) [11], [12]. Such cooperative assembly structures prepared using intermolecular hydrogen bonding have subsequently found various practical uses, such as visual detection of melamine in raw milk and infant formula [13], preparation of precursors for imprinted and hybrid silica materials with molecular recognition properties [14], preparation of promising precursor materials of graphitic carbon nitride (g-CN) enabling optimization of the texture and photoelectric properties [15] and hydrothermal synthesis of organic channel structures [16]. Moreover, it was found that cyanuric acid reprograms the self-assembly of poly(adenine) DNA, RNA and peptide nucleic acid (PNA) to form novel nucleic acid structures [17].

Figure 1

(A) 1:1 complex between cyanuric acid and melamine; (B–D) cooperative anion-π and N-H···anion binding interactions between (thio)cyanuric acid derivatives and halide anions.

In recent years, however, cyanuric acid derivatives have drawn attention of researchers interested in noncovalent anion-aromatic bonding, the poorly explored counterpart of cation-π interactions [18]. The term “anion-π interactions” has been coined by Frontera and coworkers to describe energetically favorable interactions between anions and electron-deficient (π-acidic) rings, such as hexafluorobenzene, trinitrobenzene and s-triazine, with a permanent positive quadrupole moment [19]. Subsequently, anion-π interactions have been exploited in fields such as supramolecular assembly, anion sensing and transport through membranes in biological systems [20], [21], [22], [23], [24], [25], [26], [27], [28]. However, despite the fact that research on synthetic anion transport systems has already grown into mature field [29], [30], [31], [32], [33], [34], the examples of synthetic anionophores that work with anion-π interactions are rather scarce. Among the most prominent functional systems are naphthalenedimide rods designed to combine active, photoinduced transport of electrons in one direction with passive anion antiport along anion-π slides [35].

Our previous contribution to this field has been the synthesis of π-acidic dithio- and thiocyanuric acid derivatives (Figure 1, structures B and C, respectively) which exhibit cooperative anion-π and N-H···anion binding interactions [36]. As can be inferred from Figure 2, presenting calculated electron-density surfaces, (thio)cyanuric acids have positive quadrupole moments perpendicular to the aromatic plane, and therefore are able to attract electron-donor species. In the present communication we wish to describe a facile synthesis of the previously unknown cyanuric acid derivatives of type D (Figure 1) and unusual polymeric (anion-π)_n interactions in crystals of 2-(2,4,6-trioxo-[1,3,5]triazinan-1-yl)ethylammonium iodide (X=I).

Figure 2

Calculated electron-density surfaces of benzene and (thio)cyanuric acids, scaling areas of highest electron density (red) to lowest (blue).

Results and discussion

The synthetic path to 2-(2,4,6-trioxo-[1,3,5]triazinan-1-yl)ethylammonium halides 3 (X=Cl), 4 (X=Br) and 5 (X=I) is presented in Scheme 1. First, the previously described 2-(methylthio)-7,8-dihydroimidazo[1,2-a]-1,3,5-triazin-4(6H)-thione (1) [37] was subjected to the reaction with methyl iodide in boiling methanol for 1 h. Then, the resulting 2,4-bis(methylthio)-6,7-dihydroimidazo[1,2-a][1,3,5]-triazine (2) was hydrolyzed by heating in aqueous solution of an appropriate hydrogen halide to give the desired product 3–5 in good yield. Structures of the newly prepared compounds 2–5 were confirmed by CHN elemental analysis as well as IR and NMR spectroscopic data (see Experimental).

Scheme 1

Preparation of compounds 2–5.

Crystallization of the iodide salt 5 from 1% aqueous HI solution provided crystals suitable for X-ray diffraction analysis. The asymmetric part of the unit cell together with the labeling scheme is presented in Figure 3. The organic cation in 5 differs in conformation with the analogous cations found in the structures of related thioxo derivatives, 2-(2-oxo-4,6-dithioxo-[1,3,5]triazinan-1-yl)ethylammonium halides of type B and 2-(2,4-dioxo-6-thioxo-[1,3,5]triazinan-1-yl)ethylammonium halides of type C [36]. In the latter ones, the conformation around N1-C7 and C7-C8 single bonds enables hydrogen bonding between the ammonium group and the halide ion placed nearly directly above the center of the electron-deficient π-system of the triazine ring. In the thioxo derivatives the halide anion exhibits anion-π interactions with one side of the triazine ring only. In turn, the 2-ethylammonium group in 5 adopts an extended conformation what prevents hydrogen bonding between the ammonium group and the anions interacting with the triazine π system of the same organic cation. Instead, the iodide anion is placed directly above the center (Cg) of the aromatic ring on both its sides with the I⁻···Cg distances of 3.524 and 3.577 Å and I⁻···Cg···I⁻ angle of 177.4° (Figure 4). Because the cyanuric acid fragment of the cation is interacting with two iodide anions and each iodide anion is interacting with two triazine rings, a polymeric chain of alternatively arranged anions and cations extending along [001] is formed through anion-π interactions (Figure 5). These are not the only specific interactions of the cation with the anion as I1 is additionally involved in three hydrogen-bonding interactions: two N-H···I⁻ interactions with the cyanuric acid fragment and one with the ammonium group of a symmetry related molecule (Figure 4). The former hydrogen bonds connect the chains into the (100) layers whereas hydrogen bonds involving the ammonium group connect the neighboring (100) layers into a three dimensional framework as illustrated in Figure 6.

Figure 3

Asymmetric part of the unit cell in 5with the atom labeling scheme.

Figure 4

Iodide anions interacting with the cation. Distances are given in Å.

Figure 5

A polymeric chain formed via anion-π interactions along [001].

Figure 6

N-H···I⁻ hydrogen bonds and anion-π interactions in 5 organizing cations and anions into a three dimensional framework – a view along the y axis.

Conclusion

We have obtained cyanuric acid derivatives 3–5 which may serve as substrates for the development of synthetic anion-π binding modules and halide transporters that can be used as models for biological anionophores or in the treatment of certain channelopathies.

Experimental

Melting points were determined using a Boetius apparatus and are uncorrected. Elemental analyses were carried out on a Perkin-Elmer 2400 CHN analyzer. IR spectra were recorded in KBr pellets on a Nicolet FT-IR spectrophotometer. ¹H-NMR (500 MHz) and ¹³C-NMR (125 MHz) were recorded using a Varian Unity 500 spectrometer in DMSO-d₆ with SiMe₄ as an internal standard. Electron-density surfaces were calculated at the B3LYP/6-31G* level of theory with use of Spartan’08 program, Wavefunction Inc. 2-(Methylthio)-7,8-dihydroimidazo[1,2-a]-1,3,5-triazine-4(6H)-thione (1) was obtained according to the procedure described previously in Ref. [37].