Chapter 18
Borohydrides as Novel Hydrogen-Bond Acceptors 1
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M. A. Zottola , L. G. Pedersen , P. Singh , and B. Ramsay-Shaw Downloaded by UNIV OF GUELPH LIBRARY on September 9, 2012 | http://pubs.acs.org Publication Date: May 5, 1994 | doi: 10.1021/bk-1994-0569.ch018
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Department of Chemistry, Duke University, Durham, NC 27705 Department of Chemistry, University of North Carolina—Chapel Hill, Chapel Hill, NC 27599 Department of Chemistry, North Carolina State University, Raleigh, NC 27695
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An X-ray crystallographic structure of N1-boronated cytosine has provided experimental evidence for stabilizing light atom to light atom contact. This work uses high level ab initio calculations on model borane systems to substantiate the claim that there is a stabilizing light atom to light atom contact. By comparison of these model systems to the water dimer it can be concluded that these light atom interactions are unusual hydrogen bond interactions.
The research focus of our lab has been the development of boronated nucleotides as potential anti-cancer agents and therapeutic agents for use in Boron Neutron Capture Therapy (BNCT)1>2. This anti-cancer therapy relies upon incorporating boronated nucleic acids into cells via specific oligonucleotide sequences. Part of our work has been to model the effect on oligonucleotide structure and dynamics induced by the presence of a boronated nucleotide. The X-Ray crystal structure of Nl-boronated cytosine (Figure 1) provided a starting point for the modeling effort. An intriguing aspect of the crystal structure shown here is the apparent close contact between the amino protons and the protons on the cyanoborane unit. Refinement of the X-Ray crystal structure included the hydrogens. The positions of all the hydrogens were able to be determined from a Fourier difference map. The crystallographically-determined interproton distance was 2.05 Â. This distance implies an overlap of these two protons van derWaals' radii. The resolution of the structure (0.71 Â) afforded a measure of confidence for the apparent close contact between the amino protons and the protons on the cyanoborane unit.
0097-6156/94/0569-0277$08.00/0 © 1994 American Chemical Society In Modeling the Hydrogen Bond; Smith, D.; ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
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MODELING THE HYDROGEN BOND
Downloaded by UNIV OF GUELPH LIBRARY on September 9, 2012 | http://pubs.acs.org Publication Date: May 5, 1994 | doi: 10.1021/bk-1994-0569.ch018
We reasoned that there could be at least two possible explanations for this close contact between the two hydrogens. The first possibility was that packing in the unit cell forced a close contact between the protons. Unit cell analysis revealed no intermolecular contacts within 4 Â that would enforce such a conformation. Thus there were no heavy atom to heavy atom contacts which could impose this conformation which forces an overlap of the hydrogen van der Waal's radii. The second possibility was that a significant attraction could exist between the amino and cyanoboranyl hydrogens. Questions then arise about the strength and type of interaction existing between these hydrogens. However, attraction between two sets of non-bonded hydrogens has not documented, to our knowledge. The remainder of this paper is devoted to determining whether such hydrogen to hydrogen contacts as seen in this crystal structure are real. Our work began with the premise that the crystal structure contains evidence for the attraction between non-bonded hydrogens. To substantiate that claim, we must first define what we mean by a hydrogen bond. Figure 2 shows the water dimer^. The characteristics of this dimer include : • A bonding motif characterized by an electronegative heavy atom, electropositive light atom, electronegative heavy atom triad. In this case the triad consists of oxygen, hydrogen and oxygen. This exemplifies the electrostatic nature of the interaction^. • The O-H—O triad of atoms deviates slightly from linearity due to overlap between the Is orbital of hydrogen and the 2p lone pair orbital on the acceptor oxygen. Despite the electrostatic component of the interaction, the geometry of the hydrogen bonded complex reflects that some covalent interaction exists between the light and heavy atoms. A third characteristic of a hydrogen-bonded systems is that the interaction energy for a series of complexes holding the hydrogen bond acceptor (donor) constant is directly related to the Br0nsted acidity (basicity) of the donor (acceptor) 5. The criteria to decide whether or not the interaction that we observe (if real) is a hydrogen bond interaction are : 1) Does the dimer have an electrostatic component? 2) Does the geometry of the complex reflect orbital overlap? 3) Does the interaction energy reflect Bransted acidities/ basicities? Our approach to examine the potential hydrogen-bond acceptor behavior of borohydrides follows : 1) We used the molecules HF, H2O and H3N to probe the hydrogen bonding potential of borazane.
In Modeling the Hydrogen Bond; Smith, D.; ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
18.
ZOTTOLA ET AL.
Borohydrides as Novel Hydrogen-Bond Acceptors 279
2) We repeated the series using imineborane (the complex of borane with methylene imine) in place of borazane, to assess the effect of the nitrogen ligand on the potential hydrogen - bonding behavior.
Downloaded by UNIV OF GUELPH LIBRARY on September 9, 2012 | http://pubs.acs.org Publication Date: May 5, 1994 | doi: 10.1021/bk-1994-0569.ch018
First, we produced an electrostatic map for the borazane molecule (ammoniaborane)6. This map reveals a region of negative charge around the borane fragment, a clearly welcome result and an expected one based on the chemical reactivity of boron hydrides. This result implies the possibility for borohydrides to act as hydrogen-bond acceptors. We examined these complexes at three basis sets?, m76-31g, hf/631g** and mp2/6-31g**. We also explored extended basis sets for the hydrogen fluoride complexes (mp2/6-311g** and mp2/6-31g(3d,2p)). In both cases minimal (-0.005Â) geometry and energy (ΔΕ
