Elsevier

Chemical Physics

Volume 333, Issues 2–3, 30 March 2007, Pages 97-104
Chemical Physics

A theoretical study of 17O, 14N and 2H nuclear quadrupole coupling tensors in the real crystalline structure of acetaminophen

https://doi.org/10.1016/j.chemphys.2007.01.011Get rights and content

Abstract

A systematic computational investigation was carried out to characterize the 17O, 14N and 2H electric field gradient, EFG, tensors in the acetaminophen real crystalline structure. To include the hydrogen bonding effects in the calculations, the most probable interacting molecules with the target molecule in the crystalline phase were considered through the various molecular clusters. The calculations were performed with the B3LYP method and 6-311++G∗∗ and 6-311+G standard basis sets using the Gaussian 98 suite of programs. Calculated EFG tensors were used to evaluate the 17O, 14N, and 2H nuclear quadrupole resonance, NQR, parameters in acetaminophen crystalline structure, which are in good agreement with the available experimental data. The difference between the calculated NQR parameters of the monomer and molecular clusters shows how much hydrogen bonding interactions affect the EFG tensors of each nucleus. These results indicate that both O–H⋯O and N–H⋯O hydrogen bonding have major influence on the NQR parameters. Moreover, the quantum chemical calculation indicated that the intermolecular hydrogen bonding interactions play an essential role in determining the relative orientation of quadrupole coupling principal components in the molecular frame axes.

Introduction

Hydrogen bonding interactions play a unique role in characterizing the structure of molecular crystals and biological systems. Due to the central importance of hydrogen bonds, HBs, in determination of the structural and chemical properties, the study of the nature of these interactions have been an interesting issue to investigate in both experimental and theoretical fields specifically in the last few decades [1], [2], [3].

Studying the nature of the intermolecular HBs in acetanilide and its derivatives, especially acetaminophen can be an interesting idea to investigate because of their key role in biosystems as a pain reliever and fever reducer drugs. Furthermore, understanding the nature of these interactions could be a crucial step to describe the functionality of these systems in biological media at molecular level. Numerous experimental techniques, including X-ray and neutron diffraction crystallography, infrared, Raman and nuclear magnetic resonance, NMR, spectroscopies have been applied to study the nature of HBs in acetanilide and its derivatives in the solid phase [4], [5], [6], [7]. Recently, Nickols and Frampton indicated through their studies that HBs have a significant role in the morphology of acetaminophen, so the crystallization of three polymorphs of acetaminophen are controlled by hydrogen bonding interactions in the solid phase [8]. In the crystalline structure, each acetaminophen molecule is linked to four neighboring acetaminophen via O–H⋯O and N–H⋯O HBs, see Fig. 1.

Since hydrogen bonding interactions are electrostatic in nature, the techniques that deal with the charge distribution around the nuclei seem to be reliable techniques to characterize the nature of HBs. Nuclear quadrupole resonance, NQR, spectroscopy is well established as a versatile technique to study the details of the electronic and nuclear charge distribution about the nucleus of interest [9], [10]. Nuclei with spin angular momentum, I, greater than one-half, I > 1/2, have the nuclear electric quadrupole moment, eQ, which interacts with the electric field gradient, EFG, tensor originated at the site of quadrupole nuclei [11]. The nuclear quadrupole coupling constant, QCC, and asymmetry parameter, ηQ are experimentally measurable NQR parameters of which the former indicates the amount of interaction of eQ with EFG tensor and the latter measures the symmetry of EFG tensor. Otherwise, availability of the EFG tensor eigenvalues of nuclei involved in the hydrogen bonding interactions can provide important information about the local bonding interactions and the strength of the intra and intermolecular HBs [12]. The experimental 17O NQR parameters of acetanilide were reported by Wu et al., previously [13].

Acetaminophen is an acetanilide derivative in which a hydroxyl group is substituted with H(4), see Fig. 1. We chose the crystalline acetaminophen in our present work for several reasons. Firstly, the crystal structure of acetaminophen has been accurately determined by X-ray diffraction study at 293 K [7]. Secondly, crystalline acetaminophen exhibits interesting hydrogen bonding features. According to the model calculations, intermolecular HBs contribute up to 30% of the total lattice energy in the crystalline acetaminophen [14]. Thirdly, as it is known, there is an essential lack of NQR parameter necessary for the characterization of 17O, 14N and 2H nuclei in acetaminophen and it can be useful to calculate these parameters on the acetaminophen crystalline structure, theoretically.

It is well known that high level quantum chemistry approaches can be used to evaluate the EFG tensors. Although the experimental studies are essential in obtaining information about the HBs, combining them with theoretical calculations can leads to better interpretation of experimental EFG tensors. Our previous theoretical studies on the amino acids, peptides and nucleic acids demonstrated the influence of hydrogen bonding interactions on the 2H, 14N and 17O NQR parameters [15], [16], [17], [18]. Moreover, Wu et al. investigated theoretically 17O NMR and NQR tensors for secondary amide functional groups in the crystal structure of acetanilide, benzanilide and N-methylbenzamide. Their results indicated that both 17O NMR and NQR tensors of an amide functional group are sensitive to the hydrogen bond environment [13].

The present work includes the investigation of hydrogen bond effects on the 17O, 14N and 2H EFG tensors of acetaminophen in its actual crystalline phase. As Fig. 1 illustrates, each acetaminophen molecule is involved in a hydrogen bond network in its crystal lattice, so the effect of neighboring molecules are included as close to the actual crystalline structure as possible. In order to obtain reasonable theoretical data compatible to the experiment as possible, these effects must be included in the calculations. However, various molecular models of acetaminophen, including the monomer, dimer, tetramer and pentamer models were considered for the EFG calculations. EFG tensors in their principal axes system, PAS, for 17O, 14N and 2H nuclei are calculated using density functional theory, DFT, approach. The computed EFG tensor eigenvalues, qxx, qyy and qzz were converted to those experimentally measurable parameters, QCC and ηQ, and tabulated in Table 1, Table 2, Table 3.

Section snippets

Computational aspects

DFT calculations were performed using Gaussian 98 suite of programs [19]. This is done for calculating the EFG tensors in their PAS systems for oxygen, nitrogen and hydrogen nuclei. Among various modern functionals for DFT calculation, the Becke’s nonlocal three-parameter exchange and correlation functional with the Lee et al. correlation functional, designated B3LYP, with 6-311++G∗∗ and 6-311+G standard basis sets were used [20], [21]. As mentioned above, the crystal structure of

Hydrogen bonding network modeling in the crystalline acetaminophen

As mentioned above, acetaminophen in its actual crystalline structure makes extensive intermolecular HBs with its neighboring molecules, to provide one with the chance to study the influence of these interactions on the EFG tensors of the oxygen, nitrogen and hydrogen nuclei. However, to study systematically the hydrogen bonding effects in the crystalline acetaminophen, we constructed several molecular models with various sizes. As shown in Table 1, Table 2, Table 3, four models were used in

Results and discussion

In this study, EFG tensors of the 17O, 14N and 2H of acetaminophen in its actual crystalline structure were calculated to investigate the influences of intermolecular hydrogen bonding interactions. To achieve the aim, the calculations were performed for various molecular models including the monomer, dimer, tetramer and pentamer of acetaminophen molecules. The hydrogen bond distances between the target molecule and its neighboring molecules in the solid phase are illustrated in Fig. 1c. EFG

Orientation of EFG principal components in the molecular frame axes

High level quantum chemical calculations have proven to be an excellent approach for obtaining EFG tensor orientations in the molecular frame axes. Previously, Wu et al. have indicated that quantum chemical calculation at B3LYP/6-311++G∗∗ level can produce reliable results for the EFG tensor orientations, although the magnitude of the individual principal components computed by this level is less accurate [37]. Therefore, at this point, it is of much interest to characterize the relative

Concluding remarks

We have presented a theoretical investigation of the 17O, 14N and 2H EFG tensors for acetaminophen in its crystalline phase. On the basis of the results obtained in this investigation, it is concluded that the EFG tensors of oxygen, nitrogen and hydrogen nuclei in the HBs are appropriate parameters to characterize the property of these interactions. Our obtained results indicated that calculated NQR parameters change via hydrogen bonding interactions within the molecular clusters. Considering

References (38)

  • I.G. Binev et al.

    J. Mol. Struct.

    (1998)
  • G. Nichols et al.

    J. Pharm. Sci.

    (1998)
  • N.L. Hadipour et al.

    Chem. Phys. Lett.

    (2002)
  • H. Behzadi et al.

    Biophys. Chem.

    (2007)
  • U. Werner et al.

    Chem. Phys. Lett.

    (1993)
  • G. Cazzoli et al.

    J. Mol. Spectrosc.

    (1990)
  • S.G. Kukolich et al.

    J. Mol. Spectrosc.

    (1971)
  • B.P. Van Eijck

    J. Mol. Spectrosc.

    (1974)
  • S.K. Amini et al.

    Chem. Phys. Lett.

    (2004)
  • A.V. Finkelstein et al.

    Protein Physics

    (2002)
  • R.S. Lipsitz et al.

    J. Am. Chem. Soc.

    (2002)
  • M. Strohmeier et al.

    J. Phys. Chem. A

    (2003)
  • S.W. Johnson et al.

    J. Phys. Chem.

    (1995)
  • M.D. Lumsden et al.

    J. Am. Chem. Soc.

    (1994)
  • E.V. Boldyreva et al.

    Acta Crystallogr. B

    (2000)
  • M.A. Rafiee et al.

    J. Comp. Aid. Mol.

    (2004)
  • C.P. Slichter

    Principles of Magnetic Resonance

    (1992)
  • A. Wong et al.

    J. Phys. Chem. A

    (2006)
  • K. Yamada et al.

    J. Am. Chem. Soc.

    (2000)
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