Seven-coordinate anion complex with a tren-based urea: Binding discrepancy of hydrogen sulfate in solid and solution states

Abstract

Structural characterization of a hydrogen sulfate complex with a tren-based urea suggests that the anion is coordinated with six NH ··· O bonds (d_N ··· _O = 2.857 (3) to 3.092 (3) Å) and one OH ··· O bond (d_O ··· _O = 2.57 (2) Å) from three receptors; however, in solution the anion is bound within the pseudocavity of one receptor.

Sulfate plays an important role in many biochemical processes.¹ The sulfate-binding protein (SBP) was structurally identified in 1985 by Pflugrath and Quiocho, in which the amino acid residues are involved in hydrogen bonding interactions to form a seven-coordinate anion complex.² In this structure, the sulfate is present in a cleft between the two lobes of SBP and bound by seven hydrogen bonds: five from peptide NH groups (Ala173, Asp11, Gly131, Gly132, Ser45), one from a tryptophan side chain NH group (Trp192), and one from a serine OH group (Ser130). Sulfate is also of significant environmental interest.³ Therefore, an increasing attention has recently been devoted to sulfate binding with synthetic receptors which include polyamines,⁴ polyamides,⁵ ureas,⁶ indoles,⁷ self-assembled metal–organic hosts,⁸ and triazolium hosts.⁹ The oxygen atoms in oxoanions are generally coordinated with two hydrogen bonds, thus sulfate with four oxygens is often found to be octacoordinated with synthetic receptors.^5a,10 Custelcean et al. have shown that a tren-based urea linked with Ag₂SO₄ is capable of binding a sulfate by twelve hydrogen bonds (d_N ··· _O = 2.8516 to 3.1741 Å),^8a which is consistent with Hay’s prediction that each oxygen could be involved in a maximum of three hydrogen bonds.¹¹ Bowman-James et al. have reported a ten-coordinate sulfate complex stabilized in a tetramide-based host with four amides (d_N ··· _O = 3.06–3.31 Å), two protonated amines (d_N ··· _O = 2.76 Å), and four H₂O molecules (d_O ··· _O = 2.71 and 2.79 Å).¹² Wu et al. have characterized a multiple coordinate sulfate complex with a tris(3-pyridyl)urea showing eleven NH ··· O hydrogen bonds (d_N ··· _O < 3.2 Å).^8b In this communication, we report a heptacoordinated hydrogen sulfate resulting from the coordination of three tren-based ureas (L) via six NH ··· O bonds (d_N ··· _O = 2.857(3) to 3.092(3) Å) and one OH ··· O bond (d_O ··· _O = 2.57(2) Å), and its solution binding studies.

The tripodal urea L was synthesized from the reaction of tren and p-cyanophenyl isocyanate in CHCl₃. Crystallographic analysis^‡ of the free urea reveals that the ligand forms a pseudo-cavity consisting of three arms (Fig. 1). One oxygen is involved in intermolecular hydrogen bonding interactions with two NH’s of another arm. The bisulfate salt was obtained from the reaction of L with H₂SO₄ in ethanol at room temperature. The salt crystallizes as [HL · (HSO₄)] where the tertiary amine is protonated. The proton on the tertiary nitrogen is pointed inside the tripodal cavity formed by the three arms, and is hydrogen-bonded with one carbonyl oxygen of a urea group (N1 ··· O34 = 2.783(2) Å). The molecule contains a singly-charged hydrogen sulfate to balance the charge of the cationic host. However, the anion is not encapsulated; it is held outside the cavity via two H-bonds of N18 ··· O1 and N21 ··· O1 (d_N ··· _O = 2.981(2) and 3.020(3) Å, respectively).

Fig. 1.

Tren-based urea (L) and its X-ray structure (1).

Examining the coordination environment of hydrogen sulfate suggests that it is coordinated with multiple hydrogen bonds comprised of several NH ··· O bonds and one OH ··· O bond in the lattice framework formed by three tren ureas (Fig. 2). The coordination environment of the anion is shown in Fig. 2, and the hydrogen bonding parameters are listed in Table 1. The nature of the hydrogen-bonding interactions involved in the complex can be evaluated from a correlation of H ··· O distance and N–H ··· O angle in the strong hydrogen-bonding interactions region of d_N ··· _O < 3.2 Å, d_H ··· _O < 2.5 Å and ∠N–H ··· O > 140°.^8b,13 It is clear that all six NH ··· O hydrogen bonds fall within the hydrogen bonding range (see Fig. S6 in ESI). This interpretation is further supported by the work from Ghosh et al. for the 14-coordinate sulfate complex of a pentafluorophenyl-substituted tripodal urea receptor (d_N ··· _O = 2.852(6) to 3.217(6) Å),^6g Custelcean et al. for the 12-coordinate sulfate within metal–organic framework (d_N ··· _O = 2.8516 to 3.1741 Å),^8a and Bowman-James for the sulfate complex of tetramide (N ··· O = 3.06–3.31 A).¹² We, therefore, conclude that hydrogen sulfate is coordinated by a total of seven hydrogen bonds comprised of six NH ··· O bonds and one OH ··· O bond (Fig. 3). While each of the three tren ureas contributes two hydrogen-bond donors via NH groups from a single arm, one tren unit acts as a hydrogen-bond acceptor through its carbonyl oxygen.

Fig. 2.

X-ray structure of the hydrogen sulfate complex with L showing seven hydrogen bonds (six NH ··· O and one OH ··· O bonds).

Table 1.

H-bonding parameters (Å, °) for the bisulfate complex of L

D—H ··· O	H ··· O	D ··· O	∠DHO
O1—H1A ··· O20a	1.79(3)	2.573(2)	178(3)
N4—H4 ··· O3b	2.15(3)	2.979(3)	169(2)
N7—H7 ··· O2b	2.12(3)	2.936(3)	171(2)
N18—H18 ··· O1	2.23(2)	2.981(2)	159(2)
N21—H21 ··· O1	2.20(2)	3.020(3)	153(2)
N32—H32 ··· O4a	2.40(2)	3.092(3)	142(2)
N35—H35 ··· O4a	2.06(3)	2.857(3)	170(2)

^a $\frac{1}{2}-\text{x},-\frac{1}{2}+\text{y},\frac{1}{2}-\text{z}$,

^b $\frac{1}{2}-\text{x},\frac{1}{2}+\text{y},\frac{1}{2}-\text{z}$.

Fig. 3.

The coordination environment of bisulfate showing seven hydrogen bonds from three ureas.

In order to evaluate the binding affinity of L for anions, ¹H NMR titration studies were performed in DMSO-d₆. The addition of n-Bu₄NHSO₄ to L resulted in a significant downfield shift of both NH signals (Δδ_max = 0.87 and 0.60 ppm), suggesting an interaction of NH groups with the anion. The change in the chemical shift of NH resonances of NMR spectra, as recorded with an increasing amount of anion solution at room temperature, gave the best fit for a 1 : 1 binding model, yielding a binding constant of log K = 3.0 (Fig. 4).¹⁴ The observed binding constant is much higher than that observed for singly-charged bisulfate in an amide-based cryptand (log K =1.83(3)).^4a The solution binding mode was further confirmed by 2D NOESY NMR experiments of both free ligand and hydrogen sulfate complex in DMSO-d₆ (Fig. 5) As shown in Fig. 5A, the free ligand shows two strong NOESY contacts between H_b ··· H_c and H_a ··· H_b, an observation which is also supported by single crystal structure of L showing distances of H_b ··· H_c = 2.30 and H_a ··· H_b = 2.08 Å. Upon the addition of bisulfate, H_c proton on aromatic ring shifts more downfield as compared to H_d, leading the reversal of the relative position of these two protons (see Fig S9a in ESI). The NOESY between H_a and H_b is absent in the complex, while the contact between H_b and H_c becomes significantly weaker; indicating a conformational change of the ligand due to encapsulation of a bisulfate anion (Fig. 6). Similar changes were reported by Schneider et al. in the optimized structure of chloride complex of a tren-based urea ligand.¹⁵ The 1 : 1 binding stoichiometry in DMSO-d₆ was further verified by the Job’s plot showing a maximum at the 0.5 mole fraction of L (see ESI).

Fig. 4.

¹H NMR titration curves of L (2 mM) with n-Bu₄ NHSO₄ (●, ▲) and ZnSO₄ (○, △) in DMSO-d₆. Net changes in the chemical shifts of NH are shown against the increasing amount of anion (20 mM). H1 = CH₂ NHCO and H2 = CONHAr.

Fig. 5.

2D NOESY NMR experiments of L in absence (A) and presence (B) of hydrogen sulfate (5 equiv.) in DMSO-d₆.

Fig. 6.

Proposed binding mode of L for hydrogen sulfate in solution.

We also performed ¹H NMR titrations for other oxoanions: SO₄₂⁻, H₂PO₄⁻, ClO₄⁻ and NO₃⁻ in DMSO- d₆.¹⁶ The results show that the host forms a strong 1 : 1 complex with SO₄²⁻ giving the binding constant of log K = 4.7 which is comparable to that observed for a pentafluorophenyl-substituted tripodal urea (K = 4.72)^6h or nitrophenyl-substituted tripodal urea log K = 4.97).^6c Clearly, an additional charge on SO₄²⁻ compared to HSO₄⁻ plays a role for stronger electrostatic interactions, resulting in a stronger binding of SO₄²⁻. The ligand also binds H₂PO₄⁻ strongly with the binding constant of log K = 4.2. On the other hand, the addition of ClO₄⁻ and NO₃⁻ did not result in any appreciable change in the NMR resonances (see ESI). Therefore, the binding largely depends on the relative basicity of the anions included in this study and is in accordance with the Hofmeister series.¹⁷

In summary, we have presented a seven coordinate complex of hydrogen sulfate formed by three tren-based receptors in solid state. The anion is coordinated with six NH ··· O bonds and one OH ··· O hydrogen bond. In contrast, the ligand was found to encapsulate a single anion within its cavity in solution, suggesting an obvious discrepancy of binding mode from that observed in solid state. While many examples exist for seven-coordinate complexes with metal ions,¹⁸ to the best of our knowledge, there is just one structure of seven-coordinate anion complex reported by Bowman-James and coworkers, where one sulfate is encapsulated by an amide-based cryptand with four hydrogen-bonds to the cryptand and three additional hydrogen-bonds to the crystalline water molecules.¹⁹ The seven coordinate complex in our case has been resulted from the packing influence of the crystal, which represents a rare example of a heptacoordinated anion with a synthetic receptor.

BT, TH and KT were supported by DOE under the Faculty and Student Teams (FaST) Program at ORNL hosted by Dr. Bruce A. Moyer. Participation of PVB and MAH was sponsored by the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences, U.S. Department of Energy. This work was supported by National Institutes of Health, Division of National Center for Research Resources, under Grant Number G12RR013459 (MAH). This material is based upon work supported by the National Science Foundation under CHE-0821357 (500 MHz NMR). The authors thank the National Science Foundation (CHE-0130835) and the University of Oklahoma for funds to acquire the diffractometer used in this work. National Science Foundation is acknowledged for a CAREER award (CHE-1056927) to MAH.