Quantifying the Effects of Halogen Bonding by Haloaromatic Donors on the Acceptor Pyrimidine

Abstract

The effects of intermolecular interactions by a series of haloaromatic halogen bond donors on the normal modes and chemical shifts of the acceptor pyrimidine are investigated by Raman and NMR spectroscopies and electronic structure computations. Halogen-bond interactions with pyrimidine's nitrogen atoms shift normal modes to higher energy and upfield shift H and C NMR peaks in adjacent nuclei. This perturbation of vibrational normal modes is reminiscent of the effects of hydrogen bonded networks of water, methanol, or silver on pyrimidine. The unexpected observation of vibrational red shifts and downfield C NMR shifts in some complexes suggests that other intermolecular forces such as π interactions are competing with halogen bonding. Natural bond orbital analyses indicate a wide range of charge transfer is possible from pyrimidine to different haloaromatic donors and computed halogen bond binding energies can be larger than a typical hydrogen bond. These results emphasize the importance in strategic selection of substituents and electron withdrawing groups in developing supramolecular structures based on halogen bonding.

A Raman Spectroscopic and Computational Study of New Aromatic Pyrimidine-Based Halogen Bond Acceptors

“…Figure 3c, Figure 9c, Figure 10c, and Figure S5 show spectral features in the vicinity of Prm's Fermi resonance composed of ν 12 and the combination band (ν 10b and ν 16b ), and its ring breathing mode ν 1 . This latter spectral feature dominates the Raman spectra of liquid, solution, and solid phase, and we have shown previously that it is very sensitive to hydrogen bonding [42,43,45], halogen bonding [21], and the transfer of electron density [48]. Contrary to the other spectral regions considered here, there are few similarities in the spectral features between Prm and its derivatives.…”

“…The symmetric and asymmetric CN stretching modes, ν 8a and ν 8b , respectively, are nearly isoenergetic in the liquid state at approximately 1565 cm -1 . Whereas ν 8a is not significantly perturbed by hydrogen bonding [42,43,45], halogen bonding [21], and electron density redistribution [48], ν 8b is very sensitive to intermolecular interactions, and is to observed to significantly blue-shift in a similar fashion to ν 1 . We previously took advantage of this phenomenon and employed hydrogen bonding with water to separate the two modes in a solution and confirm their assignments [42].…”

“…A halogen bond is a noncovalent interaction involving the net attraction between an electrophilic region of a halogen atom (e.g., bromide or iodide; C-Br or C-I) on one molecule, and the nucleophilic region of another or the same molecule [20]. Electron withdrawing atoms such as fluorine or similar functional groups on the halogen bond donor have been shown to significantly enhance this σ-hole interaction, to the point of even energetically competing with hydrogen bonding interactions [21]. Halogen bond acceptors typically incorporate a heterocyclic nitrogen atom, with the lone pairs playing a central role in the noncovalent interaction.…”

“…Our research groups have studied the Raman vibrational spectra and the effects that noncovalent interactions and charge delocalization have on the normal modes of pyrimidine for over a decade [21,[42][43][44][45][46][47][48][49]. We have quantified hydrogen bonding interactions involving pyrimidine with water, methanol, ethylene glycol, and other species [42,43,45]; argyrophilic interactions with silver island films [48]; solid-state interactions between pyrimidine molecules [44]; and halogen bonding interactions with a variety of donors [21]. We have also demonstrated that the Raman spectra of pyrimidine in the solid-state is only weakly perturbed from that of the liquid, and that computational chemistry could be utilized to accurately assign normal modes and assess the effects of weak interactions in the solid-state [44].…”

Studies of Halogen Bonding Induced by Pentafluorosulfanyl Aryl Iodides: A Potential Group of Halogen Bond Donors in a Rational Drug Design

“…On the other hand, the addition of pyridine or TBAC to iodobenzene leads to a decrease of the chemical shift of the carbon atom bonded to the iodine atom. This observation could be explained by the competitive interaction of the intermolecular π-π interaction[67] (with pyridine) or the cation-π interaction[68] (with tetra (n-butyl) ammonium cation), although this explanation needs further experimental support. Despite this, pentafluoroiodobenzene is an activated halogen bond donor but iodobenzene is not.We next examined the titration experiments of a series of SF5-substituted iodobenzenes 1a-d. As mentioned above, the changes in chemical shift of pyridine titration are much smaller than those of TBAC titration, while the occurrence of halogen bonding is fundamentally the same.…”