Effects of Supramolecular Architecture on Halogen Bonding between Diiodine and Heteroaromatic N-Oxides

Article abstract of DOI:10.1021/acs.cgd.7b01734

Cocrystallization of diiodine with a series of heteroaromatic N-oxides produced three types of halogen-bonded associates: (a) alternating chains comprising I₂ molecules bridged by oxygen atoms of N-oxides of pyridine, quinoline, or 4-methylpyridine; (b) discrete 2:1 complexes, in which diiodine links a pair of acridine N-oxide molecules; and (c) amphoteric 1:1 adducts, in which one end of each diiodine molecule is halogen-bonded to N-oxide of 4-methoxypyridine or 4-chloroquinoline, and another diiodine's end forms contacts with the other I₂ molecules. In all cases, halogen bonds between diiodine and N-oxides are characterized by nearly linear I-I···O angles, close to perpendicular dihedral C-N-O···I angles and N-O···I angles of about 110°. The halogen bond length in the 1:1 adducts is about 0.3 ? shorter than those in the 2:1 associates and in the infinite chains. Computational analyses confirmed that the variations in I···O separations are related predominantly to the distinct effects of halogen bond competition in different supramolecular associates. Experimental and computational data also indicated that coordination of the second diiodine to the same oxygen atom of N-oxide has a smaller effect on the halogen bond length and energy than coordination of the second N-oxide to another iodine atom in the I₂ molecule.

Full text of DOI:10.1021/acs.cgd.7b01734

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Article
Effects of supramolecular architecture on halogen
bonding between diiodine and heteroaromatic N-oxides
Yakov P. Nizhnik, Alex Sons, Matthias Zeller, and Sergiy V. Rosokha
Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b01734 • Publication Date (Web): 10 Jan 2018
Downloaded from http://pubs.acs.org on January 12, 2018
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Effects of supramolecular architecture on halogen bonding
between diiodine and heteroaromatic N-oxides
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Yakov P. Nizhnik,a Alex Sons,b Matthias Zeller,c Sergiy V. Rosokhab*
a Bioo Scientific, 7050 Burleson Rd, Austin, TX 78744.
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b Department of Chemistry, Ball State University, Muncie, IN, USA, 47306.
c1Department of Chemistry, Purdue University, West Lafayette, IN, USA, 47907.
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Abstract
Co-crystallization of diiodine with a series of heteroaromatic N-oxides produced three types of halogen-
bonded associates: a) alternating chains comprising I2 molecules bridged by oxygen atoms of N-oxides of
pyridine, quinoline or 4-methylpyridine; b) discrete 2:1 complexes, in which diiodine links a pair of
acridine N-oxide molecules; and c) amphoteric 1:1 adducts, in which one end of each diiodine molecule is
halogen-bonded to N-oxide of 4-methoxypyridine or 4-chloroquinoline, and another diiodine's end forms
contacts with the other I2 molecules. In all cases, halogen bonds between diiodine and N-oxides are
characterized by nearly linear I-I···O angles, close to perpendicular dihedral C-N-O···I angles and N-
O···I angles of about 110o. The halogen-bond length in the 1:1 adducts are about 0.3 Å shorter than those
in the 2:1 associates and in the infinite chains. Computational analyses confirmed that the variations in
I···O separations are related predominantly to the distinct effects of halogen-bond competition in different
supramolecular associates. Experimental and computational data also indicated that coordination of the
second diiodine to the same oxygen atom of N-oxide has a smaller effect on the halogen bond length and
energy than coordination of the second N-oxide to another iodine atom in the I2 molecule.
Sergiy V. Rosokha
Ball State University
Chemistry Department
Muncie IN 47306
Phone: 765-285-8615
Fax: 765-285-6505
E-mail: svrosokha@bsu.edu
https://sites.google.com/site/srosokha/
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Effects of supramolecular architecture on halogen bonding
between diiodine and heteroaromatic N-oxides
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Yakov P. Nizhnik,a Alex Sons,b Matthias Zeller,c Sergiy V. Rosokhab*
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a Bioo Scientific, 7050 Burleson Rd, Austin, TX 78744.
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b Department of Chemistry, Ball State University, Muncie, IN, USA, 47306.
c1Department of Chemistry, Purdue University, West Lafayette, IN, USA, 47907
Abstract
Co-crystallization of diiodine with a series of heteroaromatic N-oxides produced three types of halogen-
bonded associates: a) alternating chains comprising I2 molecules bridged by oxygen atoms of N-oxides of
pyridine, quinoline or 4-methylpyridine; b) discrete 2:1 complexes, in which diiodine links a pair of
acridine N-oxide molecules; and c) amphoteric 1:1 adducts, in which one end of each diiodine molecule is
halogen-bonded to N-oxide of 4-methoxypyridine or 4-chloroquinoline, and another diiodine's end forms
contacts with the other I2 molecules. In all cases, halogen bonds between diiodine and N-oxides are
characterized by nearly linear I-I···O angles, close to perpendicular dihedral C-N-O···I angles and N-
O···I angles of about 110o. The halogen-bond length in the 1:1 adducts are about 0.3 Å shorter than those
in the 2:1 associates and in the infinite chains. Computational analyses confirmed that the variations in
I···O separations are related predominantly to the distinct effects of halogen-bond competition in different
supramolecular associates. Experimental and computational data also indicated that coordination of the
second diiodine to the same oxygen atom of N-oxide has a smaller effect on the halogen bond length and
energy than coordination of the second N-oxide to another iodine atom in the I2 molecule.
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Introduction
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Although halogen bonding became a focus of supramolecular chemistry only during the last two
decades, this intermolecular interaction could be identified in the adducts of diiodine with ammonia going
back over a century.[1-8] Following seminal UV-Vis studies of the complexes between I2 and aromatic
molecules by Benesi and Hildebrand,[9] and X-ray crystallographic analysis of Br2 associates with
dioxane by Hassel et al.,[10] a number of molecular complexes involving halogenated electrophiles were
characterized during the 1960s and 1970s.[11-17] Many of these associates (referred to as charge-transfer
or donor/acceptor complexes) involved diiodine. In particular, several UV-Vis studies demonstrated that
I2 molecules form strong associates with aliphatic or aromatic N-oxides.[14-17] Somewhat later, Kubota
et al. established the substituent effect on electronic spectra and equilibria constants of a large series of
complexes of diiodine with pyridine-N-oxides.[18]
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Diiodine, the original halogen-bond donor, is capable of forming a variety of associates.[7, 19-22]
This diversity is related to the ability of I2 molecule to simultaneously participate in several halogen bonds
in which it can serve both as a halogen-bond donor and acceptor. Based on the extensive analysis of
halogen-bonded associates involving dihalogens and interhalogens, Pennington et al. pointed out several
structural modes of interaction between diiodine and electron donors, B, i.e.: 1) simple adducts, BI-I; 2)
bridged, BI-IB; 3) amphoteric, BI-II-I; 4) bridged amphoteric, BI-II-II-IB; and 5) ionic,
D+-I  I- modes.[7] Heteroaromatic N-oxides, on the other hand, are excellent halogen-bond acceptors
due to the strong nucleophilicity and exceptional steric accessibility of their oxygen atoms in comparison
with their parent heterocycles, as well as their ability to form more than one contact with a halogen-bond
donor.[23-27] For example, halogen-bonded chains formed by 4,4'-dipyridyl N,N'-dioxide and 1,4-
diiodotetrafluorobenzene described in 2001 by Resnati, Metrangolo and co-workers comprised the
shortest O···I intermolecular distance (2.75 Å) reported at that moment in the crystallographic
literature.[19] More recently, even shorter I-O separations of about 2.3 – 2.4 Å were found by Rissanen et
al. in the complexes of several N-oxides with N-iodosuccinimide or N-iodosaccharin.[24] Aakeröy and
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co-workers employed bifurcated halogen bonds between iodofluorobenzenes and N-oxides (i.e. bonds in
which one oxygen atom participates in two different C-I···O interactions) for the deliberate assembly of
molecular polygons in the solid state.[25]
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Since the N-oxide group stabilizes both Wheland and Meisenheimer complexes, heteroaromatic N-
oxides are more reactive than their parent heterocycles in both electrophilic and nucleophilic
processes.[28, 29] This makes them valuable catalysts, mild nucleophilic oxidants and useful inter-
mediates in synthetic organic chemistry.[29-33] Reactivity of N-oxides can be modulated by Lewis and
Brønsted-Lowry acids.[34-39] We have shown previously that coordination of the v-acceptor, BF3, to the
oxygen atom of the N-O group enhances the π-acceptor strength of 4-nitropyridine- and 4-nitroquinoline
N-oxides, and the latter form ternary complexes in which N-oxide plays a dual role of both Lewis acid
and base.[40] The latest publications demonstrated that various reactions of heteroaromatic N-oxide can
be also catalyzed by diiodine.[31,32]
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The ability of heteroaromatic N-oxides and diiodine to form strong halogen bonds and the
possibility of the use of such bonding in catalysis raise the interest to the structural and electronic features
of the complexes comprising these two molecules. The authors of the earlier studies suggested several
possible modes of their interactions, such as -bonding of diiodine with oxygen or π-bonding with a
parallel arrangement of the diiodine molecule above the aromatic ring of N-oxide.[41-46] These
suggestions, however, were based on the results of NMR, IR and/or UV-Vis measurements. Despite the
fact that the discussion of the complexes of diiodine with N-oxides has continued for more than 50
years,[14,15,18, 41-46] the definitive elucidation of their structures via X-ray structural analysis is
lacking.
Thus, in our current work, we intend to explore the modes of interaction between heteroaromatic N-
oxides and diiodine. This goal will be achieved via X-ray structural and computational characterization of
the association between the diiodine and a series of acridine, quinoline and pyridine N-oxides illustrated
in Chart 1 (together with their abbreviations).
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Chart 1.
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X = H: PyO
X = CH3: MePyO Y = Cl: ClQnO
X = OCH3: MeOPyO
Y = H: QnO
AcrO
Beside clarification of the structural features of the molecular complexes between diiodine and
heteroaromatic N-oxides, X-ray crystallographic studies of their associates makes it possible to evaluate
the effect of the supramolecular architecture on the structural characteristics of halogen bonding. In
addition, a variety of potential modes of interactions between diiodine and heteroaromatic N-oxides
provide vast opportunities for crystal engineering based on the combination of these two molecules.
Results and Discussion
Addition of solid heteroaromatic N-oxides to saturated solutions of diiodine in dichloromethane
immediately led to a change of color of these solutions from violet to brown (due to the well-known blue
shift of the absorption band of I2 upon its complexation with electron donors[18]). Cooling or slow
evaporation of these solutions afforded dark yellow to red-brown crystals of adducts between diiodine and
N-oxides suitable for single-crystal X-ray measurements (see Experimental section for details). They
show three types of halogen-bonded solid-state associates: a) alternating donor/acceptor chains, b)
discrete 2:1 complexes, as well as c) 1:1 adducts between heteroaromatic N-oxides and diiodines (the
latter also show contacts between amphoteric iodine atoms which are not involved in halogen bonding
with N-oxides).
In particular, when a dichloromethane solution containing equimolar amounts of pyridine-N-oxide
and diiodine was prepared at room temperature and then cooled down and kept at -60o C for several days,
brown crystals were formed. FT-IR measurements of these crystals show that a strong band of the parent
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N-oxide around 1250 cm-1 (which is related to the N–O stretching vibrations) disappeared and new bands
appeared in the 1200-1100 cm-1 range (see Figure S1 in the Supporting Information). Such spectral
changes were assigned earlier to the complex formation between diiodine and N-oxides. [46] X-ray
structural analysis of these crystals revealed that they comprise pyridine-N-oxide and diiodine in a 1:1
molar ratio. Similar to the diiodine adducts with dioxane reported by Bock,[47] the pyridine N-oxides and
diiodine moieties form infinite (parallel) alternating chains showing short interatomic I···O contacts
(Figure 1, see crystal packing in Figure S2 in the Supporting Information). In the case of N-oxides,
however, diiodine molecules are linked by bridging oxygen atoms which form two halogen bonds (such
coordination was earlier referred to as a bifurcated halogen bond [25]). Geometric characteristics of the
halogen bonds in these co-crystals are listed in Table 1.
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Figure 1. Alternating donor/acceptor chains in the PyO•I2 (top) and MePyO•I2 (bottom) co-crystals.
Halogen bonds are shown as the light blue lines.
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Table 1. Selected bond distances (Å) and angles (o) in the co-crystals of diiodine with N-oxides
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I-I…O,o
175.04
171.46
173.82
174.04
174.26
168.44
170.66
168.70
171.52
171.99
174.16
177.68
177.62
172.58
178.59
174.27
174.34
N-O-I,o
109.12
108.47
106.70
106.17
104.43
106.89
103.62
99.56
C-N-O-I, o
77.91
88.04
76.19
85.40
89.17
86.85
83.70
82.16
88.04
89.51
77.11
74.51
72.59
72.49
76.19
79.60
63.51
Type
N-oxide
dI···O, Å
2.684
2.791
2.755
2.754
2.661
2.874
2.686
2.747
2.698
2.805
2.704
2.724
2.743
2.810
2.686
2.393
2.499
PyO
Chain
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MePyO
Chain
107.78
103.13
125.31
116.30
114.06
120.99
118.09
113.63
111.71
QnO
Chain
AcrO
2:1
1:1
1:1
MeOPyO
ClQnO
The chains formed by diiodine and pyridine N-oxide comprise four crystallographically
independent I···O contacts. The interatomic distances between the corresponding oxygen and iodine
atoms vary from 2.68 Å to 2.79 Å, i.e., they are about 20-25 % shorter than the sum of the van der Waals
radii of oxygen and iodine of 3.50 Å.[48] The I–I···O angles within these pairs are about 171o -175o. Both
these characteristics are typical for strong halogen bonds.[4-7] The C-N-O···I dihedral angles in the
pyridine N-oxide/diiodine pairs are about 80o, and the N-O···I angles in the 106 – 109o range (i.e. the I2
molecules approach oxygen atoms of N-oxides from above of the aromatic rings).
Co-crystals of diiodine with 4-methylpyridine-N-oxide comprise very similar donor/acceptor chains
(Figure 1 and Figure S2 in the Supporting Information). The geometric characteristics of halogen bonds in
this system are also close to that in the PyO•I2 co-crystals (Table 1). Likewise, co-crystals of diiodine
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with quinoline N-oxide showed chains of alternating halogen-bonded molecules. These interlocked zigzag
chains form layers in which stacks of N-oxide molecules from four different chains are separated by I2
molecules (Figure 2).
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Figure 2. Interlocked zigzag chains in the QnO•I2 co-crystals. (Note: different colors designate different
chains, halogen bonds and short contacts between stacked quinoline N-oxide molecules are shown as light
blue lines, hydrogen atoms are omitted for clarity).
The angles between the planes of neighboring quinoline N-oxide molecules are 2.27 o and 6.07 o (i.e.
they are almost co-planar). The neighboring molecules are somewhat shifted and turned relatively to each
other. For example, the pyridine ring of one molecule overlap with pyridine ring of one of its neighbor, so
the distances between centroids of these ring is 3.686Å, and the shortest C…C distances is 3.297 Å. The
distance between the phenylene rings of the same molecules is 4.454 Å. In the other, crystallographically
independent, neighboring pairs of QnO molecules, pyridine rings are located over phenylene moieties, with
the distances between their centroids of 3.765Å and 3.764 Å (and the shortest C…C distances is 3.391 Å).
The N-O···I angles in these crystals are somewhat larger than those in the chains formed by diiodine with
pyridine N-oxide and 4-methylpyridine N-oxide (Table 1). The lengths of four crystallographically
independent I···O halogen bonds in the QnO•I2 chains vary in the 2.7 Å – 2.8 Å range, which is essentially
the same as that in their PyO•I2 and MePyO•I2 analogues.
Co-crystals of diiodine with 4-methoxypyridine and 4-chloroquinoline N-oxides show a strikingly
different pattern of halogen bonding. In both cases, each I2 molecule forms only one halogen bond with
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the oxygen atom of the N-O group, and vice versa (Figure 3). The distance between the oxygen and
iodine atoms in the MeOPyO·I2 co-crystals (2.393 Å) is about 32 % shorter than the sum of the van der
Waals radii of oxygen and iodine. The distances between the iodine atoms at the other end of the I2
A
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B
Figure 3. Crystal structures of the 1:1 MeOPyO·I2 (A) and ClQnO·I2 (B) adducts.
molecule (i.e. between the iodine atoms which do not form halogen bonds with oxygen) are 3.941 Å. This
value is within 0.5 % of their van der Waals separation. In essence, there are no short intermolecular
contacts at this diiodine’s end.
The geometric measure of the halogen bond strength, RXY = dX···Y/(rX + rY) (where dX···Y is the
separation between the donor and acceptor atoms, X and Y, and rX and rY are their van der Waals radii)
for the I···O bond in the MeOPyO·I2 co-crystals is 0.683. This value is close to that in the shortest O···I
halogen bond (RXY = 0.662) found recently by Rissanen et al. in the complexes of N-iodosaccharin with
pyridine-N-oxide derivatives.[24] Notably, these very short halogen bonds were observed (in the current
study and in Rissanen’s work[24]) in the 1:1 donor/acceptor adducts, in which each iodine-containing
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molecule is halogen-bonded to one N-oxide and vice versa. Overall, the distances between oxygen and
diiodine in these adducts are much closer to the I-O covalent bond length (~2.05Å) than to the van der
Waals separation of oxygen and iodine atoms (3.50 Å).
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In the ClQnO·I2 co-crystals, the O···I bond distance of 2.499 Å (Table 1) is almost as short as in the
complexes of diiodine with 4-methoxypyridine N-oxide. The contacts between the diiodine ends which
are not bonded to the oxygen atoms in these co-crystals are also, at first glance, similar to that in the
MeOPyO·I2 analogues (Figure 3 and Figure S3 in the Supporting Information). Yet, a closer look at the
interatomic I···I distances and angles at the diiodine ends which are not halogen-bonded to the oxygen
atoms reveals some differences between these two systems. Specifically, in the ClQnO·I2 co-crystals, the
intermolecular I···I separations are 3.860 Å. This value is 4 % shorter than the sum of the van der Waals
radii of two iodines. Also, in this case, one I-I···I angle is 175o yet another angle is 77o (as compared to
154o and 118o in the MeOPyO·I2 co-crystals). In other words, in the ClQnO·I2 co-crystals, the top of one
iodine forms a rather short contact with the side of another iodine (Figure 3B). Such arrangements
(together with the interatomic distances) suggest weak halogen bonding between the iodine atoms in the
ClQnO·I2 co-crystals. Interestingly, these amphoteric iodine atoms participate simultaneously in two
halogen bonds. Each iodine serves as a halogen-bond donor in one of the I···I bonds, and it serves as a
halogen bond acceptors in another bond. As a result, the iodine molecules form infinite iodine ribbons
separated by N-oxide molecules (Figure 4, and Figure S3 in the Supporting Information).
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Figure 4. X-ray structure of ClQnO·I2 showing diiodine ribbons enclosed by the ClQnO molecules.
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The halogen-bonding pattern between iodine atoms in the ClQnO·I2 co-crystals is akin to that observed
in the structure of pure diiodine.[49] The unique crystal structure of I2 (determined as early as 1928) shows
the infinite planar 2D-sheets of the halogen-bonded diiodines. Each I2 molecule within these sheets (in the
crystal structure of diiodine) is involved in four halogen bonds , i.e. amphoteric iodine atoms on both sides of
diiodine serve simultaneously as halogen-bond donors and acceptors (see Figure S3 in the ESI). In
comparison, the diiodine ribbons in the ClQnO·I2 co-crystals are enclosed by the 4-chloroquinoline N-oxides
moieties (Figures 3B and 4). As such, they could be considered as the 0.6 nm-wide fragments of the I2 sheets
inside the core formed by the N-oxides. The intermolecular I···I distances in the related MeOPyO·I2 co-
crystals are practically the same as their van der Waals separations, and I-I···I orientations deviate much
more strongly from the linear and perpendicular angles (vide supra). So, despite similarity in the diiodine
arrangements (Figure 3), there is hardly any halogen bonding between the diiodines in the MeOPyO·I2 co-
crystals. Still, since the halogen bonds between iodine atoms in the ClQnO·I2 co-crystals are relatively weak
(and the effects of two I···I bonds to one iodine probably somewhat compensate each other due to the dual
donor/acceptor role of the iodine atom in these bonds), the I···O distance in the 1:1 adduct of diiodine with
4-chloroquinoline N-oxide is close to the corresponding value in the 1:1 MeOPyO·I2 complex.
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Co-crystals of diiodine with acridine-N-oxide show another type of halogen-bonded associates.
They comprise 2:1 complexes in which an I2 molecule links two acridine N-oxides (Figure 5). As such,
Figure 5. Structure of 2:1 complexes formed by AcrO and I2 molecules.
they represent an intermediate case between the chains (in which each donor forms bonds with two
acceptors and each acceptor forms bonds with two donors) and 1:1 adducts (in which one diiodine is
bonded to one N-oxide molecule). It is interesting to note, therefore, that the O···I distance in these 2:1
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complexes (2.686 Å) is close to that in the infinite chains in which each oxygen atom of N-oxide and each
I2 are involved in two (bifurcated) halogen bonds (Table 1).
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The data in Table 1 indicate that the variations of the I-I···O, N-O···I and C-N-O···I angles in the
solid-state associates between diiodine and heteroaromatic N-oxides are rather minor. In other words,
regardless of the supramolecular architectures, the mutual orientations of the halogen-bonded donor and
acceptor are similar. However, the lengths of the halogen bonds differ significantly in the 1:1 adduct from
that in the infinite chains and the 2:1 adducts. To verify if such bond-length variations are related to the
changes in the type of association (leading to competition of two halogen bonds at the same donor or
acceptor), we carried out a computational analysis of the halogen-bonded complexes under study.
DFT (M062X/def2tzvpp) optimizations of the 1:1 N-oxide/I2 pairs produced structures in which
mutual donor/acceptor arrangements were similar to those measured in the solid state associates, as
illustrated for the diiodine adduct with 4-methylpyridine N-oxide in Figure 6. In the experimental and
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Figure 6. Structures of the MePyO·I2 complexes from X-ray analysis (left) and from computations (right).
calculated MePyO·I2 complexes, the diiodine molecule is halogen-bonded to the oxygen atom of the N-
oxide. The N-O···I angles vary from 99 o to 106o in the crystallographically independent solid-state
MePyO·I2 associates, and this value is 106o in the calculated complex. The dihedral C-N-O···I angles
vary from 83o to 89o in the solid state complexes, and the value of the corresponding angle in the
calculated structure is essentially 90o. However, the halogen bond length in the calculated 1:1 dyad (2.604
Å) is about 0.15 Å shorter than the average I···O distance in the solid-state chains formed by the I2
molecules and 4-methylpyridine N-oxides (Table 1).
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Interaction energies and geometric characteristics of the calculated 1:1 complexes between
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diiodine and the heteroaromatic N-oxides are listed in Table 2. All calculated complexes show strong
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Table 2. Interaction energies (E) and selected geometric characteristic of the diiodine complexes with
heteroaromatic N-oxides.
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N-O-I,o
I-I···O,o
C-N-O-I, o
E, kcal/molc
-8.70
dI···O, Å
PyO
MePyO
QnO
2.637
2.604
2.603
2.624
2.562
2.596
110.4
105.8
108.8
107.9
107.3
107.9
176.0
175.5
177.1
175.9
175.8
178.0
62.6
89.7
66.7
89.4
81.1
89.4
-9.33
-8.93
ClQnO
MeOPyO
AcrO
-8.62
-10.04
-9.47
a) From M062X/def2tzvpp computations. b) E = Ecomp – (ENO + EI2) + BSSE, where Ecomp, ENO and EI2 are sums of
the electronic and zero-point energies of the complex, N-oxide and I2 and BSSE is a basis set superposition error.
halogen bonding, with the interactions energies varying from about -8.6 kcal/mol to -10.0 kcal/mol. The
I-I···O angles in these complexes are close to 180o, N-O···I angles are about 108o and dihedral C-N-O···I
angles are mostly close to 90o. These angles are similar to the corresponding values measured in the solid-
state associates (Table 1), which confirms that the M062X/def2tzvpp computations reproduce very well
the mutual arrangements of the donor and acceptor in the halogen-bonded complexes.
Comparison of the E and dI···O values in Table 2 indicates that changes in the calculated I···O
distances for different N-oxides generally follow the variations of the interaction energy (i.e., the complexes
with more negative E are characterized by shorter halogen bonds). A closer inspection of these variations
suggests that they are related to the strength of the electron donors. Quantitatively, the latter can be
expressed via their oxidation potentials, E1/2ox. The values of E1/2ox obtained from electrochemical
measurements of a number of heteroaromatic N-oxides were reported earlier.[50,51] Together with the data
from Table 2, they allow to check the relationship between dI..O and E1/2ox . However, the E1/2ox values of the
N-oxides under study and the calculated I···O separations in their complexes with diiodine vary within a
fairly narrow ranges of E1/2ox = 1.6  0.2 V vs SCE and dI···O = 2.60  0.04 Å (see Table 2 and Table S2 in the
Supporting Information). Thus, to verify the relationship between dI..O and E1/2ox in a wider range, we carried
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out M062X/def2tzvpp computations of the halogen-bonded complexes of diiodine with an extended series of
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heteroaromatic N-oxides. As illustrated in Figure 7, the halogen-bond lengths,
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2.7
R² = 0.92
2.5
2.3
0.5
1
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2
2.5
E1/2ox, V vs SCE
Figure 7. Relationship between E1/2ox of heteroaromatic N-oxides and dI···O in the calculated 1:1
complexes, (), as well as in the solid-state 1:1 adducts (■), 2:1 complex (●) and infinite chains (▲). (See
Table S2 in the Supporting Information for the E1/2ox values and dI..O in the calculated complexes).
dI···.O, within these calculated complexes show a rather strong correlation (R2 = 0.92) with the oxidation
potentials of the heteroaromatic N-oxides.[52] This figure also demonstrates that the dI···O values for 1:1
adducts obtained from the X-ray measurements of the MeOPyO·I2 and ClQnO·I2 co-crystals are located
far below the calculated trend line. The dI···O values measured experimentally for the (solid-state) infinite
chains and 2:1 complex are located above the calculated trend line.
It should be mentioned that the crystallographically non-equivalent I···O contacts in the infinite
chains formed by diiodine with PyO, MePyO or QnO molecules vary within rather large ranges (0.1 Å -
0.2 Å). Such variations of the experimental halogen-bond length are probably related to the very shallow
minima in the dependencies of energies of the complexes on intermolecular separations. As illustrated for
the complex between 4-methylpyridine N-oxide and diiodine in Figure 8, the increase or decrease of dI···O
by about 0.1 Å from its optimal value (corresponding to the global minimum) is accompanied by an
energy change of only 0.25 kcal/mol. As such, in the solid state,
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0
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dI…O, A
Figure 8. Dependence of the energy of halogen bonded complexes on the I···O distance relative to the
energy of the fully-optimized complex. Insert: variation of the energy near the minimum.
this halogen bond length can be easily adjusted by crystal forces. Most importantly, the difference between the
halogen bond lengths in the 1:1 adducts (squares in Figure 7), and those in the 2:1 complex (circle) and in the
infinite chains (triangles), is substantially larger than the variations of dI···O within one type of supramolecular
complex. Furthermore, this large distinction between the dI···O values for different modes apparently is not
related to the oxidation potentials of N-oxides or to the values of the most negative potential on the surface of
the N-oxides or the energies of their HOMOs (see Figure S4 in the Supporting Information[52]). For example,
the oxidation potential of 4-chloroquinoline N-oxide is slightly higher (i.e., it is a weaker donor) than that of
quinoline N-oxide (Table S2). Yet, the halogen-bond length in the 1:1 adduct formed by 4-chloroquinoline N-
oxide is about 0.3 Å shorter than the dI···O measured in the chains formed by diiodine with quinoline N-oxide.
In fact, the difference between the average bond length in the infinite chains and that measured in the 1:1
complexes is larger than the limiting dI···O values in the calculated complexes (despite more than 1.5 V
difference in the E1/2ox of the corresponding N-oxides). In other words, the halogen bonding of diiodine with
the second N-oxide molecules has more pronounced effect on the halogen-bond length than the changes in the
electron-donor strength of N-oxide. This supports the conclusion that such differences are related primarily to
the changes in the mode of supramolecular donor/acceptor interaction (1:1 adduct vs 2:1 complexes or
alternating chains).
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The values of dI···O are definitely expected to change with variations of E1/2ox (or Vmin), as indicated by
the dependences in the calculated values in Figure 8 and Figure S4 in the Supporting Information.
However, in order to verify these relationships experimentally, it is necessary to establish variations of
such bonds within the same mode of association. Furthermore, to draw reliable conclusions, an analysis
of structural data for a wider series of N-oxides is needed (including much weaker and stronger electron
donors, e.g. 4-nitropyridine N-oxide and 4-dimethylaminopyridine N-oxide).[53]
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It is also noticeable that the experimental halogen-bond length in the 2:1 acridine N-oxide/diiodine
complex (in which I2 is bonded to two oxygen atoms, but the latter participate in only one halogen bond)
is much longer than that in the 1:1 complexes. (Similar differences in halogen bond length in 2:1 and 1:1
complexes of 1,3-diiodo-5,5-dimethylhydantoin were reported recently by Fourmigue et al. [54]) In fact,
the I···O distance of 2.686 Å in the 2:1 complex of AcrO with I2 is almost the same as the dI···O values in
the infinite chains in which each diiodine and each oxygen atom participates in two halogen bonds. This
suggests that the elongation of intermolecular distances in the infinite chains as compared to that in the
1:1 adducts is related mostly to the competition of two halogen bonds at the same diiodine molecule. This
suggestion is supported by the results of the calculations on the 2:1 and 1:2 complexes between pyridine
N-oxide and diiodine. The energies and intermolecular distances in these complexes, as well as in the
corresponding 1:1 dyad are shown in Figure 9.
2.832Å
2.716 Å
2.637 Å
2.716 Å
2.832Å
9.23 kcal/mol
8.55 kcal/mol
7.34 kcal/mol
-E
Figure 9. Interaction energies (per one halogen bond) and I···O distances in the 1:1. 1:2 and 2:1
complexes between PyO and I2 molecules (from M062X/def2tzvpp computations).
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Figure 9 demonstrates that bonding of two I2 molecules to one oxygen atom decreases the energy of
each halogen bond by about 0.7 kcal/mol as compared to that in the 1:1 complex. However, if two N-
oxides are bonded to one diiodine, the energy of each bond is decreased by about 1.9 kcal/mol (i.e. the
difference is almost three times larger). The changes of the bond lengths follow the trend observed in the
changes of energies. Specifically, bonding of two diiodines to one oxygen atom of an N-oxide leads to an
increase of halogen bond length by about 0.079 Å. In comparison, bonding of two N-oxides to one
diiodine results in an increase of the bond length by 0.195 Å. Thus, both experimental and computational
data indicate that coordination of a second diiodine to the same oxygen atom of an N-oxide has a smaller
effect than coordination of the second N-oxide to another iodine atom of the I2 molecule.
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To clarify the reason for these differences, we calculated the effects of the coordination of diiodine
to a heteroaromatic N-oxide on the properties of both interacting molecules. Within the framework of the
electrostatic (-hole) model,[4-6, 55] halogen bonding between these two molecules is related to the
attraction of a -hole on the surface of the I2 molecule to the area of negative potential on the surface of
the oxygen atom of the N-oxide, as illustrated in Figure 10 (left).
+8.8
+32
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-33
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-40
Figure 10. ESPs of PyO, diiodine and their halogen-bonded complex (numbers show values of ESP in
kcal/mol, see Figure S5 in ESI for additional views of the ESPs of the complex and its components).
The coordination of diiodine to N-oxide results in polarization of both halogen-bonded molecules.
Accordingly, the -hole on the non-coordinated iodine atom is characterized by a much lower value of
maximum positive potential Vmax = 8.8 kcal/mol, as compared to Vmax = 32.1 kcal/mol, calculated for the
free I2 molecule. On the other hand, pyridine N-oxide shows the most negative potential Vmin = - 43.0
kcal/mol on the surface of the oxygen atom. Coordination of the diiodine molecule changes this value to -
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33.2 kcal/mol. So, halogen bonding between diiodine and N-oxide is accompanied by a much more
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pronounced modification of the Vmax value on the other end of the I2 molecule than the change of Vmin on
the surface of the oxygen atom of N-oxide (participating in this halogen bonding). Therefore, halogen
bonding of the second N-oxide to halogen-bonded diiodine is affected by the first halogen bond more
substantially than coordination of the second diiodine to the same oxygen atom of N-oxide.
While consideration of the ESP surfaces allows for explaining variations of the dI···O with the change
of the stoichiometry, it overlooks the question of the donor/acceptor arrangements in their complexes. In
particular, the most negative potentials on the surfaces of the N-oxide under study are observed on the top
of the oxygen atoms along the extension of the N-O covalent bonds. Thus, to maximize electrostatic
attraction, the diiodine is expected to approach the oxygen along the N-O bond (resulting in an N-O···I
angle of about 180o). Yet, the experimental and calculated complexes are characterized by an N-O···I
angle of about 110o regardless of the nature of N-oxide or mode of interaction. Similar (roughly
tetrahedral) angles were observed earlier in the halogen-bonded complexes of iodinated molecules with
selenides, and they were related to the electron-pair donation from the HOMO of selenium to the LUMO
of iodine.[56] Consideration of molecular-orbital shapes of heteroaromatic N-oxides and diiodine together
with the geometries of their complexes (as illustrated for MePyO·I2 in Figure 11) suggests that analogous
HOMO/LUMO interactions play a significant role in the halogen bonding of these molecules.[57-59] The
changes in the bond-length in the 2:1 and 1:2 complexes in this case can be related to the larger effect of
halogen bonding on the LUMO of diiodine than on the HOMO of the N-oxide (Table S3 in the
Supporting Information).
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Figure 11. Frontier (HOMO/LUMO) orbital shapes of 4-methylpyridine-N-oxide
and diiodine and their role in formation of the halogen-bonded complex.
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Conclusion.
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X-ray crystallographic and computational analyses established three major types of halogen-bonded
associates between heteroaromatic N-oxides and diiodine, i.e., infinite donor/acceptor chains, 2:1
associates in which I2 molecule links two N-oxide molecules and (more or less isolated) 1:1 adducts
between N-oxides and diiodines. Regardless of the supramolecular architecture of the co-crystals, the
relative orientations of the halogen-bonded donors and acceptors are similar. However, the interatomic
I···O distances in the 1:1 adducts are ~0.3 Å shorter compared to that in the 2:1 associates or infinite
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chains. These distinctions are related to the competition of two I···O halogen bonds, and the fact that the
effects of coordination of two N-oxides at the opposite ends of I2 molecule are more pronounced than that
of diiodines coordinated to the same (bridging) oxygen atom.
In general, the variations of the bond lengths in various types of supramolecular complexes
(resulted from cooperation or competition of co-existing intermolecular interactions [60-66]) are not
surprising. For example, structural characteristics of the extensive series of halogen-bonded complexes of
dihalogens and interhalogens, which were reviewed by Pennington et al.[7], indicate that halogen-bond
lengths in the 1:1 adducts are usually shorter than the separations between analogous atoms in infinite
donor/acceptor chains. However, the earlier examples of such variations were focused on one reactant or
involved significant changes in the nature of halogen-bond donor or acceptor or type of halogen
bonding.[7,54,60-66] In comparison, the current work provides examples of the changes in bond length in
mono- and ditopic bonding of both halogen bond donors and acceptors in 1:1, 2:1 associates and infinite
chains formed by diiodine with the analogous N-oxides. Moreover, we have shown that while the
calculated halogen-bond lengths are related to the strength of the electron donors, the changes of
supramolecular architectures have more pronounced effects on intermolecular separations in the solid-
state adducts. It thus underscores the importance of accounting for variations in supramolecular
architectures in comparison of intermolecular bond lengths obtained from the solid-state measurements,
as well as in their correlations with the data from solution, gas-phase or computational studies.
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Experimental Section
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Materials. Commercially available PyO, MePyO, MeOPyO, QnO and 4-nitroquinoline N-oxide were
used without additional purification. ClQnO was prepared by the reaction of 4-nitroquinoline N-oxide
with HCl.[67] AcrO was prepared by the oxidation of acridine by peroxobenzoic acid in CH2Cl2 and
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purified using flash chromatography on silica gel (eluent CH2Cl2:MeOH 10:1), following recrystallization
from an ethanol-water (2:1) solution and subsequent drying in a desiccator over P2O5 for a week.[68]
Co-crystals of diiodine with various N-oxides were prepared by cooling or slow evaporation of
dichloromethane solutions containing 1:1 molar ratios of both components. In particular, to prepare
adducts with PyO, MePyO and ClQnO, diiodine (102 mg, 0.40 mmol) was dissolved in 4 mL of
anhydrous dichloromethane and the equivalent amounts (0.40 mmol) of the corresponding N-oxides were
added to these solutions. After the starting materials were dissolved, the solutions were kept at -30oC for
one day and then at -60oC for two days. This resulted in the formation of crystals suitable for X-ray
structural measurements. To prepare co-crystals of diiodine with AcrO, QnO and MeOPyO, the
dichloromethane solutions containing analogous amounts of components were slowly evaporated in a
desiccator in the presence of mineral oil.
Single crystals of diiodine with MeOPyO, AcrO, and QnO were coated with mineral or Fomblin oil
and quickly transferred to the goniometer head of a Bruker Quest diffractometer with a fixed chi angle
and a molybdenum radiation sealed tube fine focus X-ray tube (λ = 0.71073 Å). Intensity data for X-ray
crystallographic analysis of diiodine associates with PyO, MePyO and ClQnO were collected at 173 K
with a Bruker SMART Apex diffractometer equipped with a CCD detector using Mo K radiation (λ=
0.71073 Å). Reflections were indexed and processed, and the files were scaled and corrected for
absorption using APEX3.[69] The space groups were assigned and the structures were solved by direct
methods using XPREP within the SHELXTL suite of programs[70] and refined by full matrix least
squares against F2 with all reflections using Shelxl2016[71] using the graphical interface Shelxle.[72] If
not specified otherwise, H atoms attached to carbon and nitrogen atoms and hydroxyl hydrogens were
positioned geometrically and constrained to ride on their parent atoms, with C-H bond distances of 0.95 Å
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for aromatic and C-H, 1.00, 0.99 and 0.98 Å for aliphatic C-H, CH2 and CH3 moieties, respectively.
Methyl H atoms were allowed to rotate but not to tip to best fit the experimental electron density. Uiso(H)
values were set to a multiple of Ueq(C) with 1.5 for CH3, and 1.2 for C-H units, respectively.
Crystallographic, data collection and refinement details are listed in Table 3. Complete crystallographic
data, in CIF format, have been deposited with the Cambridge Crystallographic Data Centre. CCDC
1588334-1588339 contain the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.
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Table 3. Crystallographic, data collection and structure refinement details
MeOPyOI2
QnOI2
AcrOI2
PyOI2
MePyOI2
ClQnOI2
Chem. formula
C9H7NO·I2
2(C13H9NO)·I2
C5H5NO·I2
C6H7NO·I2
C9H6ClNO·I2
C6H7NO2I2
378.93
Mr
398.96
Monoclinic
P21/c
644.22
Monoclinic
P21/c
348.9
362.93
433.40
Monoclinic
P21
Cryst. system
Space group
Monoclinic
P21/c
Triclinic
Triclinic
P1
9.132(5)
9.374(5)
10.755(6)
91.833(10)
90.119(10)
107.266(9)
878.7(8)
4
P1
9.6417(14)
10.9728(17)
14.931(3)
68.470(3)
88.067(5)
86.905(3)
1467.1(4)
6
a (Å)
b (Å)
12.5018 (8)
4.2736 (3)
18.8796 (12)
90.00
10.5555 (6)
15.4203 (8)
13.7263 (7)
90.00
7.1316 (10)
11.1071 (16)
14.426 (2)
90.00
9.762(2)
6.1078(15)
10.743(3)
90.00
c (Å)
 (°)
108.5094 (17)
90.00
104.715 (2)
90.00
101.547 (5)
90.00
116.064(4)
90.00
 (°)
 (°)
V (Å3)
956.52 (11)
4
2160.9 (2)
8
1119.6 (3)
2
575.4(4)
2
Z
T, K
150
150
150
173
173
173
 (mm-1)
n measd
n indpt
n obs [I >2(I)]
R [F2 > 2(F2)]
wR(F2)
S
6.53
5.78
2.84
7.09
6.37
5.99
27011
34754
18241
9486
18523
4093
3654
6538
4044
4971
8505
2799
3416
4847
3303
3467
6741
2637
0.021
0.047
0.025
0.062
0.036
0.035
0.046
0.114
0.054
0.177
0.087
0.092
1.25
1.07
1.09
1.07
0.99
1.05
CCDC
1588338
1588339
1588337
1588335
1588336
1588334
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Computations. Quantum-mechanical calculations were carried out using the Gaussian 09 suite of
programs.[73] Geometries of N-oxides, diiodine and halogen-bonded complexes were optimized in the
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gas phase via DFT calculations with the M06-2X functional and the def-TZVPP basis set.[74] To obtain
fully-optimized complexes, geometry optimizations were carried out without constraints using the default
convergence criteria for Gaussian 09. The absence of imaginary frequencies confirmed that the optimized
structures represent true minima. Dependence of the energies of the halogen-bonded complexes on dI···O
was obtained via constrained optimization with the fixed I···O distances. The energies of interaction for
all dyads were determined as: E = Ecomp – (ENO + EI2) + BSSE, where Ecomp, ENO and EI2 are sums of the
electronic and ZPE of the complex, N-oxide and I2, and BSSE is a basis set superposition error.[75]
Frontier orbital shapes were evaluated at 0.02 isovalues and electrostatic potentials were calculated on the
0.001 electrons bohr-3 molecular surfaces. Energies and atomic coordinates of the calculated complexes
are listed in the Supporting Information.
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Acknowledgements. We thank the National Science Foundation for the financial support of this work
(grant CHE-1607746). We also thank W. Borley for the assistance in the analysis of computational data,
J.J. Lu for the assistance in the X-ray measurements of PyO•I2, MePyO•I2 and ClQnO•I2, and the R. A.
Welch Foundation for the financial support of these measurements. X-ray structural measurements of
QnO·I2, MeOPyO·I2, and AcrO·I2 were supported by the National Science Foundation through the Major
Research Instrumentation Program under Grant No. CHE 1625543 (funding for the single crystal X-ray
diffractometer).
Supporting Information. FT-IR spectra of adducts (Figure S1), crystal packing of PyO•I2 and MePyO•I2
(Figure S2), diiodine ribbons in MeOPyO·I2, ClQnO·I2 and I2 crystals (Figure S3); correlation between
d
I···O and Vmin or E(HOMO of N-oxides (Figure S4), ESP surfaces of PyO, diiodine and their halogen-
bonded complex (Figure S5), calculated energies of adducts and their components (Table S1), E1/2ox, Vmin
and E(HOMO) of N-oxides and dI···O in their complexes (Table S2), effect of halogen bonding on
HOMO/LUMO energies (Table S3), atomic coordinates of calculated complexes.
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importantly, the experimental I···O distances in the 1:1 adducts are arranged below, and in 2:1 complexes
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For Table of Contents Use Only
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Title: Effects of supramolecular architecture on halogen bonding
between diiodine and heteroaromatic N-oxides
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Authors: Yakov P. Nizhnik, Alex Sons, Matthias Zeller, Sergiy V. Rosokha,*
TOC graphic
X-ray structural characterization of co-crystals of the original halogen bond donor, diiodine, with
heteroaromatic N-oxides demonstrated that I…O separations in their 1:1 adducts are about 0.3 Å shorter
than that in the 2:1 associates or in the infinite chains, and these variations are related largely to the
distinct effects of halogen-bond competition in different supramolecular associates.
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