Systematic Experimental and Computational Studies of Substitution and Hybridization Effects in Solid-State Halogen Bonded Assemblies

Article abstract of DOI:10.1021/acs.cgd.8b00398

A quantitative assessment of the substituent, hybridization, and crystal-packing effects on the electronic, structural, and vibrational properties of halogen bonded systems is presented. Through a combined experimental and theoretical approach employing R

Full text of DOI:10.1021/acs.cgd.8b00398

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Systematic Experimental and Computational Studies of Substitution
and Hybridization in Solid-State Halogen Bonded Assemblies
Suong T. Nguyen, Thomas L. Ellington, Katelyn E Allen, John D. Gorden, Arnold
L. Rheingold, Gregory S. Tschumper, Nathan I Hammer, and Davita L. Watkins
Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.8b00398 • Publication Date (Web): 30 Mar 2018
Downloaded from http://pubs.acs.org on March 30, 2018
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Systematic Experimental and Computational Studies
of Substitution and Hybridization in Solid-State
Halogen Bonded Assemblies
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Suong T. Nguyen,‡,a Thomas L. Ellington,‡,a Katelyn E. Allen,‡,a John D. Gorden,b Arnold L.
Rheingold,c Gregory S. Tschumper,a* Nathan I. Hammer,a* and Davita L. Watkinsa*
aDepartment of Chemistry and Biochemistry, University of Mississippi, University, Mississippi,
38677-1848, United States
bDepartment of Chemistry and Biochemistry, Auburn University, Auburn, Alabama, 36849-5312,
United States
cDepartment of Chemistry, University of California, San Diego, La Jolla, California 92093-0358,
United States
ABSTRACT. A quantitative assessment of the substituent, hybridization, and crystal-packing
effects on the electronic, structural, and vibrational properties of halogen bonded systems is
presented. Through a combined experimental and theoretical approach employing Raman
spectroscopy, X-ray crystallography, and density functional theory (DFT), a series of solid-state
iodobenzene and iodoethynylbenzene derivatives substituted with electron withdrawing groups (-
F2, -(CF3)2, -F5, and -(NO2)2) and their complexes with two pyridine-based building blocks are
characterized. Structural analysis via X-ray crystallography and DFT computations suggests that
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these 1:1 molecular assemblies are not only driven by halogen bonding, but also by other
energetically competitive noncovalent interactions, such as -stacking. The magnitude of the -
hole localized around the C–I bond in the isolated XB donors and the interaction strength in the
complexes unambiguously depend on the nature of the substituents on the donors and the
hybridization of the carbon atom in the C–I bond. However, the vibrational C–I stretching
frequency in the halogen bond donors and/or the change in that frequency accompanying XB
formation are not solely controlled by those two effects, but also by the coupling between the C–I
stretch and other modes associated with the substituents on the donors and the presence of various
energetically competitive non-XB contacts in the solid co-crystals. In turn, this study highlights
the importance of conducting a comprehensive electronic and structural analysis of not only the
halogen bond but also other interactions present in the surrounding solid-state environment.
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INTRODUCTION
Research in crystal engineering and material science has revealed that noncovalent
interactions play crucial roles in controlling the nanoscale architectures while also enhancing bulk
properties.1-6 Whereas hydrogen bonding has been extensively studied in the literature, the rising
alternative–halogen bonding is less commonly discussed despite its applications in various
chemical fields7-12 such as medicinal chemistry13-15 and organic synthesis.16,17 A halogen bond
(XB) is classified as a noncovalent interaction between an electrophilic region on a halogen atom
(X) and a nucleophilic region on a Lewis base, typically in the form of a nitrogen, oxygen, or sulfur
atom.18 In this case, the halogen-containing molecule is referred to as the XB donor while the
Lewis base is the XB acceptor. The anisotropic redistribution of electron density as the C–X bond
forms results in a localized region of positive electrostatic potential (ESP) that is aligned with the
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C–X covalent bond (i.e., the -hole)19-21 and a belt-like region of negative ESP that is found
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orthogonal to the C–X bond.22 As such, the emergence of an electropositive -hole affords nearly
collinear intermolecular interactions that are thermodynamically stable, with interaction energies
comparable to those of hydrogen bonding.23 Although here, the term “XB” concerns the
intermolecular interaction of the -hole of a XB donor and a XB acceptor (e.g., type-I XB), the
occurrence of a second type of XB is also possible through the intermolecular interaction of that
-hole and the electronegative belt of another XB donor (e.g., type-II XB).24 The strength of a XB
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interaction depends on the electropositive region associated with the -hole and can be tuned via
modification of the halogen atom itself or the donor substituents. That is, as the halogen atom
becomes more polarizable (I > Br > Cl >> F) and/or the XB donor substituents become more
electron withdrawing, the -hole becomes more electropositive, typically resulting in stronger XB
interactions.21,23,25
With increasing interests in this tunable noncovalent interaction, research has been focused
on quantitative techniques used to accurately characterize XB interactions involving the
-hole.26-31 Among those, spectroscopic analyses – via infrared (IR), Raman, and nuclear magnetic
resonance (NMR) spectroscopy – have been the most widely adopted because they are sensitive
enough to detect signatures of XB formation.24,32-37 Studies employing these spectroscopic
techniques typically correlate either vibrational (i.e., the C–X stretching modes) or chemical shifts
associated with XB formation to the magnitude of the -hole and thus, the strength of the
interaction.24,38-41 Although these procedures do serve as useful tools for describing and estimating
the interaction strength of XBs, they are typically adopted when studying a systematic series of
XB dimers that are not influenced by a complex environment, unlike those seen in XB co-
crystals.42 Fundamental analyses of XB driven assemblies suggest that the impact of additional
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factors, such as the environment surrounding XB, can lead to more complicated behaviors.
Metrangolo and co-workers provided some early insight into this issue when they detected an
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unexpected high-frequency chemical shift upon XB formation from the solid-state N NMR
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spectrum while attempting to evaluate the donor hierarchy, which they attributed to some
unidentified non-XB interactions.37 We have also observed similar anomalous behavior in a
previous investigation into the electronic and spectroscopic properties of solution-phase XBs in
the form of a downfield shift in the 13C NMR spectrum of a XB complex between pyrimidine and
pentafluorobenzene bromide which was suggested to stem from secondary interactions imposed
by the surrounding media.30 In a separate study, we showed that the presence of numerous
energetically competitive non-XB intermolecular interactions in solid-state XB co-crystals
resulted in complex crystal packing patterns and therefore, affected the properties of XB
interactions in those assemblies.43
Despite the number of unusual chemical shifts and/or vibrational complexation shifts
associated with XB formation reported in the literature, to the best of our knowledge, there has not
been any study that interrogates the influence of competitive non-XB intermolecular interactions
on the vibrational properties of XBs. That prompted us to probe not only the substituent and
hybridization effects but also the impact of other concurrent non-XB contacts on the molecular
properties of XB interactions in the solid-state. Single crystal X-ray structural analyses provided
insights into the packing patterns of co-crystals as well as the geometrical parameters of all XB
and non-XB interactions. Due to its low IR intensity in the fingerprint regions (100–500 cm–1), the
C–I stretching modes associated with XB interactions were detected via high resolution Raman
spectroscopy.40,44-46 Electronic structure theory computations were performed to explore the nature
of the -hole on the iodine atom of the XB donor, aid in the assignment of the C–I stretching mode
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from the experimental Raman spectra, and determine the energetics of the pairwise contacts
present in each co-crystal.
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EXPERIMENTAL AND COMPUTATIONAL METHODS
Crystal Growth and X-ray Crystallography
Co-crystals were prepared in duplicate at a 1:1 XB acceptor:donor ratio by dissolving XB acceptor
and donor in a chlorinated solvent (dichloromethane or chloroform) in a borosilicate glass vial.
The resulting mixtures were ultrasonicated for 10 minutes. The open vial was placed in a secondary
vial containing n-hexane or n-pentane. Using a vapor diffusion method, crystals were allowed to
form at −5 °C over 3-7 days. Co-crystallization was confirmed through the comparison of melting
points between the co-crystals and their corresponding monomers (i.e., both XB acceptors and
donors if they exist in the solid-state). A difference in the melting point of ca. 14 °C between the
co-crystals and the monomers was observed. Additional evidence of co-crystallization was also
obtained using IR spectroscopy. In combination with X-ray diffraction, the presence of XB
interactions between the acceptors and donors was confirmed. A summary of the melting point
and IR spectroscopic results can be found in the SI.
Geometries obtained from crystal analyses are in good agreement with those reported in
the literature.36,47 Crystal investigation and data collection were conducted using a Bruker Kappa
diffractometer with Mo Kα (λ = 0.71073 Å) radiation. Reflections were indexed by an automated
indexing routine built in the APEXII program suite. The data analyses were carried out in Olex2
version 1.248 using the program SHELXTL and in Discovery Studio Visualize 2016.
Non-hydrogen atoms were refined with anisotropic thermal parameters while hydrogen atoms
were introduced at calculated positions based on their carrier/parent atoms. Crystal data and
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structure refinement parameters for all XB complexes are reported in the SI. The CCDC numbers
for the single crystal X-ray structures of each co-crystal are as follows: 1590272, 1590273,
1590264, 1590265, 1590274, 1590275, 1590276, 1502497, 1502498, 1502499, and 1502500.
Crystal data. (NO2)2BI-PyrTF: C19H12IN3O5S (M =521.28 g/mol): monoclinic, space group P21/c
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(no.
14), a =
12.157(2) Å, b =
11.475(2) Å, c =
14.470(3) Å, β =
108.05(3)°, V =
1919.1(7) Å3, Z = 4, T = 100.0 K, μ(CuKα) = 14.470 mm-1, Dcalc = 1.804 g/cm3, 11718
reflections measured (7.648° ≤ 2Θ ≤ 136.646°), 3503 unique (Rint = 0.0419, Rsigma = 0.0357) which
were used in all calculations. The final R1 was 0.0285 (I > 2σ(I)) and wR2 was 0.0731 (all data).
(NO2)2BI-PyrT2: C19H12IN3O4S2 (M =537.34 g/mol): monoclinic, space group P21/c (no. 14), a =
5.826(2) Å, b = 7.991(2) Å, c = 41.935(8) Å, β = 91.01(3)°, V = 1952.0(9) Å3, Z = 4, T = 100.0 K,
μ(CuKα) = 15.182 mm-1, Dcalc = 1.828 g/cm3, 10920 reflections measured (4.214° ≤ 2Θ ≤
136.766°), 3532 unique (Rint = 0.0547, Rsigma = 0.0589) which were used in all calculations. The
final R1 was 0.0562 (I > 2σ(I)) and wR2 was 0.1385 (all data).
F5BI-PyrTF: C19H9F5INOS (M =521.25 g/mol): orthorhombic, space group P212121 (no. 19), a =
5.8783(2) Å, b = 7.6445(2) Å, c = 39.6751(13) Å, V = 1782.87(10) Å3, Z = 4, T = 180.45 K, μ(Mo
Kα) = 1.973 mm-1, Dcalc =1.9418 g/cm3, 22280 reflections measured (4.1° ≤ 2Θ ≤ 55.76°), 4248
unique (Rint = 0.0233, Rsigma = 0.0197) which were used in all calculations. The final R1 was 0.0165
(I>=2u(I)) and wR2 was 0.0380 (all data).
F5BI-PyrT2: C19H9F5INS2 (M =537.32 g/mol): monoclinic, space group P21 (no. 4), a =
12.7948(4) Å, b = 5.8398(2) Å, c = 13.2832(4) Å, β = 109.251(1)°, V = 937.01(5) Å3, Z = 2, T =
180.45 K, μ(Mo Kα) = 1.984 mm-1, Dcalc = 1.9043 g/cm3, 23669 reflections measured (3.24° ≤
2Θ ≤ 54.2°), 4141 unique (Rint = 0.0350, Rsigma = 0.0296) which were used in all calculations. The
final R1 was 0.0210 (I>=2u(I)) and wR2 was 0.0469 (all data).
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(NO2)2BAI-PyrTF43: C21H12IN3O5S (M =545.30 g/mol): monoclinic, space group P21/c (no.
14), a = 19.084(4) Å, b = 30.968(6) Å, c = 14.021(3) Å, β = 94.66(3)°, V = 8259(3) Å3, Z =
16, T = 100.0 K, μ(CuKα) = 13.485 mm-1, Dcalc = 1.754 g/cm3, 70152 reflections measured
(4.646° ≤ 2Θ ≤ 136.906°), 14885 unique (Rint = 0.0697, Rsigma = 0.0511) which were used in all
calculations. The final R1 was 0.0486 (I > 2σ(I)) and wR2 was 0.1176 (all data).
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̅
(NO2)2BAI-PyrT2 : C21H12IN3O4S2 (M =561.36 g/mol): triclinic, space group P1 (no. 2), a =
8.3335(4) Å, b = 11.1648(6) Å, c = 12.4716(6) Å, α = 101.7030(10)°, β = 102.3030(10)°, γ =
107.2490(10)°, V = 1037.81(9) Å3, Z = 2, T = 100.0 K, μ(MoKα) = 1.779 mm-1, Dcalc =
1.796 g/cm3, 13674 reflections measured (3.986° ≤ 2Θ ≤ 56.578°), 5133 unique (Rint = 0.0379,
Rsigma = 0.0400) which were used in all calculations. The final R1 was 0.0240 (I > 2σ(I))
and wR2 was 0.0616 (all data).
F2BAI-PyrTF43: C21H12F2INOS (M =491.28 g/mol): monoclinic, space group P21/n (no. 14), a =
10.681(2) Å, b = 4.221(2) Å, c = 40.107(8) Å, β = 92.85(3)°, V = 1805.7(10) Å3, Z = 4, T = 100.0
K, μ(CuKα) = 15.293 mm-1, Dcalc = 1.807 g/cm3, 12096 reflections measured (4.412° ≤ 2Θ ≤
137.396°), 3284 unique (Rint = 0.0399, Rsigma = 0.0309) which were used in all calculations. The
final R1 was 0.0296 (I > 2σ(I)) and wR2 was 0.0766 (all data).
43
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F2BAI-PyrT2 : C21H12F2INS2 (M =507.34 g/mol): triclinic, space group P1 (no. 2), a =
4.0288(9) Å, b =
11.599(3) Å, c =
20.709(4) Å, α =
102.070(8)°, β =
92.784(7)°, γ =
93.486(9)°, V = 942.7(4) Å3, Z = 2, T = 100.0 K, μ(MoKα) = 1.944 mm-1, Dcalc = 1.787 g/cm3,
16735 reflections measured (3.6° ≤ 2Θ ≤ 56.43°), 4633 unique (Rint = 0.0510, Rsigma = 0.0500)
which were used in all calculations. The final R1 was 0.0351 (I > 2σ(I)) and wR2 was 0.0799 (all
data).
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(CF3)2BAI-PyrTF: C23H12F6INOS (M =591.30 g/mol): triclinic, space group P1 (no. 2), a =
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9.0121(8) Å, b = 10.0224(8) Å, c = 24.324(2) Å, α = 81.838(3)°, β = 79.565(3)°, γ =
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89.127(4)°, V = 2138.7(3) Å3, Z = 4, T = 100.0 K, μ(MoKα) = 1.664 mm-1, Dcalc = 1.836 g/cm3,
33610 reflections measured (4.106° ≤ 2Θ ≤ 56.63°), 10344 unique (Rint = 0.0334, Rsigma = 0.0373)
which were used in all calculations. The final R1 was 0.0356 (I > 2σ(I)) and wR2 was 0.1053 (all
data).
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̅
F5BI-PyrTF: C21H9F5INOS (M =545.25 g/mol): triclinic, space group P1 (no. 2), a =
8.3624(10) Å, b = 9.1257(11) Å, c = 12.6353(14) Å, α = 89.285(4)°, β = 80.621(4)°, γ =
88.933(4)°, V = 951.14(19) Å3, Z = 2, T = 100 K, μ(MoKα) = 1.854 mm-1, Dcalc = 1.904 g/cm3,
15770 reflections measured (4.938° ≤ 2Θ ≤ 56.578°), 4670 unique (Rint = 0.0374, Rsigma = 0.0436)
which were used in all calculations. The final R1 was 0.0315 (I > 2σ(I)) and wR2 was 0.0721 (all
data).
̅
F5BAI-PyrT2: C21H9F5INS2 (M =561.31 g/mol): triclinic, space group P1 (no. 2), a =
5.0851(2) Å, b = 12.6790(6) Å, c = 15.6054(7) Å, α = 98.3090(10)°, β = 97.1630(10)°, γ =
99.8620(10)°, V = 969.28(7) Å3, Z = 2, T = 100.0 K, μ(MoKα) = 1.923 mm-1, Dcalc =
1.923 g/cm3, 11979 reflections measured (2.668° ≤ 2Θ ≤ 50°), 3392 unique (Rint = 0.0279, Rsigma
=
0.0227) which were used in all calculations. The final R1 was 0.0164 (I > 2σ(I)) and wR2 was
0.0444 (all data).
Computational Methods
Full geometry optimizations and harmonic vibrational frequency computations with IR intensities
and Raman activities were performed on the XB donors, acceptors, and the corresponding model
complexes. The fully optimized geometries of the dimer complexes and corresponding fragments
were used to compute binding energies (Ebind = Eocopmt plex – Eopt – Eoacpcteptor), while the vibrational
donor
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frequencies were used not only to verify whether each structure was a minimum (i.e., ni = 0) on
the potential energy surface but also to compare to the experimental Raman spectra. A full natural
bond orbital (NBO)49-56 analysis was performed to determine if a qualitative relationship exists
between the magnitude of electron density transfer (||) of each XB acceptor and donor pair in
the model XB complexes and the vibrational frequency shifts. The maximum values of
electrostatic potential corresponding to the -hole on the XB donor’s iodine atom
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(i.e., VS,max, which is commonly used to quantify the magnitude of the -hole 24) were computed
on the isolated XB donors. A set of single point energy computations, with and without the
Boys-Bernardi counterpoise (CP) procedure,57,58 was performed on the pair wise contacts found in
the experimental XB crystal structures in order to determine their interaction energies
xtal
complex
xtal
donor
xtal
(Eint = E
– E
– E
). The NBO analysis that was carried out on our model systems
acceptor
was extended to the pairwise contacts present in the experimental XB crystal structures.
All computations were performed using the Gaussian 09 software package and, where
applicable, the analytic gradients and Hessians available therein.59-61 The geometry optimizations,
vibrational frequency computations, and NBO analyses all used the global hybrid M06-2X62
density functional in conjunction with a double-zeta correlation consistent basis set augmented
with diffuse functions on all atoms (aug-cc-pVDZ) and a relativistic pseudopotential on iodine
centers (aug-cc-pVDZ for H, C, N, O, F, S and aug-cc-pVDZ-PP for I; denoted aVDZ).59,60,63 All
Ebind values are computed at the M06-2X/aVDZ level of theory. The set of single energy point
computations employed the same M06-2X density functional with the analogous triple-zeta basis
set and pseudopotential (aug-cc-pVTZ(-PP); denoted aVTZ).59,60,63 As such, all reported Eint values
are determined using the average of the necessary electronic energies (with and without CP
procedure) from the M06-2X/aVTZ level of theory. The Eint values, with and without the CP
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procedure, and the average between the two, can be found in the SI. These prescriptions were
selected based on the extensive calibration by Kozuch and Martin.64 The values of VS,max were
determined using a critical point analysis within the Multiwfn package.65 Additional details
regarding these computations along with the optimized Cartesian coordinates and harmonic
vibrational frequencies with Raman activities and IR intensities of each XB donor, acceptor, and
their corresponding complexes can be found in the SI.
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Raman Spectroscopy
A Horiba Scientific LabRAM HR Evolution Raman Spectroscopy system with charge coupled
device (CCD) camera detection was used for the acquisition of solution and solid phase Raman
spectra. The confocal microscope and high throughput 800 mm single stage spectrometer of the
LabRAM HR Evolution Raman Spectrometer allowed for high-resolution imaging of the
co-crystals as well as optimum spectral acquisition of all monomers and co-crystals. Spectra were
obtained using a 785 nm diode laser and both 600 gr/mm and 1800 gr/mm diffraction gratings,
thus allowing for accurate peak assignments with a spectral resolution of less than 1 cm–1. The
spectrum of each solid sample was optimized by locating a flat, semitransparent region of the
sample with a high potential for scattering utilizing the motorized stage and video features of the
Raman spectrometer. For liquid samples, a macro-Raman accessory was utilized. To account for
potential variations when comparing the solution-phase monomers to the solid-state co-crystals,
temperature-controlled Raman spectra were acquired using a Linkam Scientific THMS600
microscope stage for all liquid samples. The temperature-controlled Raman procedure used here
is similar to the one recommended by Herrebout.66
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RESULTS AND DISCUSSION
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Design and Synthesis of XB donors and acceptors
Design. Initially proposed for solid-state material devices, the XB acceptors (Figure 1b),
4-(5-(furan-2-yl)thiophen-2-yl)pyridine (PyrTF) and 4-([2,2’-bithiophen]-5-yl)pyridine (PyrT2),
were co-crystallized with iodobenzene and iodoethynylbenzene derivatives (i.e., XB donors;
Figure 1a). PyrTF and PyrT2 represent the derivatives of common organic semiconducting
building blocks.67-69 The pyridyl moiety is incorporated to guide the highly directional self-
assembly of XB components. The planarity and rigidity of the backbone of conjugated thiophene
and furan provide the means for the intermolecular overlap of -orbitals in the solid-state, inducing
an interplay of XB and -stacking interactions that can be further utilized for crystal engineering
and material applications.70,71 Due to the high polarizability of iodine, iodobenzene derivatives are
chosen as XB donors. The use of electron withdrawing substituents on the donors, possessing a
strong inductive effect (e.g., -F, -(NO2)2, and -(CF3)2), not only aids in the tuning of the interaction
strength, but also affords 3D architectures due to their capacity to simultaneously participate in
additional intermolecular contacts.36,43,72 Furthermore, the hybridization of the carbon atom in the
C–X bond of the XB donor influences the strength of the intermolecular interaction, in which the
higher s-character of the Csp–X induces a repositioning of the electronegative belt on the halogen
atom towards the triple bonded carbon atom, C≡Csp–X, and further increases the electropositive
region on halogen atom.
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Figure 1. Molecular structures and point group symmetries of each XB (a) donor and (b) acceptor
Synthesis. The BI donors (i.e., BI, F2BI, (CF3)2BI, F5BI and (NO2)2BI) were purchased from
commercial sources and used without further purification. The synthesis of the XB acceptors
(PyrTF and PyrT2) and two BAI donors (F2BAI and (NO2)2BAI) was reported in a previous
work.43 Additional detailed procedures to prepare BAI, F5BAI, and (CF3)2BAI can be found in
the SI. In general, Sonogashira coupling between substituted iodobenzene and
trimethylsilylacetylene
in
the
presence
of
catalytic
amounts
of
tetrakis(triphenylphosphine)palladium and copper (I) iodide in toluene and diisopropylamine
afforded the trimethyl(phenylethynyl)silane derivatives in good yield (69–71%). The
trimethylsilyl group was then substituted with iodine by treating the compound with silver fluoride
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and N-iodosuccinimide in anhydrous acetonitrile in the absence of light. F5BAI was afforded in
70% yield; while BAI and (CF3)2BAI were synthesized in 68% and 77% yield, respectively, by
using a modified procedure (see the SI).
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Electronic Properties of XB Donors
Figure 2. ESP maps and VS,max values of the (a) BI and (b) BAI XB donors using an electron
isodensity of 0.001 e–/Bohr3 at the M06-2X/aVDZ level of theory. VS,max values correspond to the
magnitude of the -hole in kcal mol–1.
In this study, we employed several computational techniques in order to accurately probe
the electronic properties of the XB donors reported in Figure 1a, which provide the reference
values needed for the characterization of XB complexes in subsequent sections. It should be noted
that although the electrostatic potential (ESP) and the electron density are sometimes used
interchangeably when discussing the magnitude of the -hole, the ESP at point r (V(r)) is not only
a function of the electron density but also the atomic nuclei as seen in the first term of Equation 1
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5
′
휌(푟 )
푍
푖
′
( )
푉 푟 =
∑
( )
− 휌 푟
|
푟 −푟
| 푑푟
(1)
∫
푖
′
|
|
푅 −푟
푖
6
7
8
9
where Zi the nuclear charge of atom i at point Ri and (r’) is the total molecular electron density.
This and other misconceptions associated with halogen bonding and the models used to describe
the interaction have been recently discussed in detail by Politzer, Murray and Clark.73,74 In general,
the magnitude of -hole (i.e., the VS,max at the iodine atom) increases with the number and the
strength of the electron withdrawing substituents on the benzene moiety of the donors (-H5 < -F2
< -(CF3)2 < -F5 < -(NO2)2) and as the hybridization of the carbon atom in the C–I bond is modified
from sp2 to sp. As can be seen in Figure 2a, the VS,max of the BI series ranges from 16.0 to 33.2 kcal
mol–1. The values tend to increase with (i) the electron withdrawing capability of the substituents
(e.g., -F2 vs. -(CF3)2) and (ii) the number of those substituents present (e.g., -F2 vs. -F5). More
electropositive -holes are observed for the BAI series, where VS,max ranges from 32.9 to 43.4
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kcal mol–1 (Figure 2b), but the trend remains the same. This enhancement of the -holes is due to
the presence of an acetylene linker, which increases the s-character of both C–I bonding and
antibonding orbitals from roughly 17% for BI donors to 30% for BAI donors, as indicated by NBO
analysis.
Structural Properties of XB Complexes
Table 1. XB intermolecular separations (RI···N in Å), angles (C–I···N in °), and percent reduction
in the sum of van der Waals radii (%rsvdW)a upon XB formation for the M06-2X/aVDZ model
dimers and the corresponding experimental complexes formed between the XB BI donors and
acceptors.
Theory
C–I···N
180
Experiment
C–I···N
169.0
Complex
(NO2)2BI-PyrTF
(NO2)2BI-PyrT2
F5BI-PyrTF
RI···N
2.92
2.92
2.86
2.86
%rsvdW
30.0
RI···N
2.89
2.91
2.89
2.78
%rsvdW
30.7
180
180
180
30.0
31.4
31.4
175.4
174.9
178.5
30.2
30.7
33.3
F5BI-PyrT2
aRelative to the sum of nitrogen (1.79 Å) and iodine (2.38 Å) van der Waals radii.75
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Co-crystals of the BI Series. A summary of the key geometrical parameters in both the
computationally derived XB dimers and the experimental XB co-crystals between the BI donors
and either acceptor is reported in Table 1. Precipitants were obtained when co-crystallization was
attempted for F2BI and (CF3)2BI with either acceptor. That observation was substantiated by their
model dimer’s weak Ebind, low %rsvdW and low || values (Table S10) relative to those for the
complexes reported in Table 1. In turn, co-crystals of (NO2)2BI and F5BI with each acceptor were
investigated. Despite using only a dimer to model the XB interaction in the crystal environment,
there is good agreement between the theoretical and experimental data. The maximum and average
absolute deviations (MAD and AAD) are 0.08 Å and 0.04 Å for RI···N, 11.0° and
5.6 ° for C–I···N, and 1.9 and 0.9 for %rsvdW, respectively. It should be noted that although -
stacking plays the most competitive role in the observed crystal structure, contacts of that class in
the BI co-crystals are severely limited in number due to the skewed orientation of the acceptors
and donors in the XB interactions (Figures 3 and 4).
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Figure 3. Packing diagram in (a) (NO2)2BI-PyrTF and (b) (NO2)2BI-PyrT2, in which both XB
and -stacking are represented. Parts of the acceptor are removed for clarity purpose.
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The 1:1 molecular assembly of (NO2)2BI-PyrTF exhibits a monoclinic structure with the
P21/c space group (Figure 3a). Its XB interaction connects the two monomers with an C–I···N of
169.0 ° and RI···N of 2.89 Å, corresponding to a %rsvdW of 30.7%. The average of M06-2X/aVTZ
computations with and without the CP procedure indicates that the interaction energy (Eint) of this
pairwise contact in the co-crystal is –6.2 kcal mol–1 (Table S72). Various parallel displaced -
stacking interactions occur between: (i) two thiophene moieties of the acceptors (3.87 Å, Eint =
–8.1 kcal mol–1), (ii) the furan residue in PyrTF and the benzene ring in (NO2)2BI (3.56 Å, Eint =
–7.4 kcal mol–1), and (iii) the pyridine moiety of PyrTF and the benzene of (NO2)2BI (4.32 Å, Eint
= –5.4 kcal mol–1) (Table S72). Other secondary interactions involving the nitro groups were also
observed (shown in greater detail in Figure S12 and Table S72).
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The crystal structure of (NO2)2BI-PyrT2 is very similar to that of (NO2)2BI-PyrTF as they
have the same P21/c space group (Figure 3b). In (NO2)2BI-PyrT2, the RI···N (2.91 Å) is slightly
longer by 0.02 Å, the C–I···N (175.4°) is closer to linearity by 6.4° (Table 1), and the XB interaction
(Eint = –6.4 kcal mol–1; Table S73) is slightly stronger by 0.2 kcal mol–1. Here, the distribution of
electron density of the donor and acceptor results in a face-to-face -stacking interaction (3.70 Å;
Eint = –8.8 kcal mol–1; Figure S13-g and Table S73) between the thiophene in PyrT2 and the
benzene moiety in (NO2)2BI. Within the same contact, the iodine atom is positioned atop the
central thiophene ring at a distance of 3.94 Å (Figure 3b). Similar to its PyrTF analog, a variety
of secondary interactions related to the nitro groups were detected in
(NO2)2BI-PyrT2 co-crystals, such as ONO ···NNO (3.36 Å, Eint = –4.4 kcal mol–1; Figure S13-b
2
2
and Table S73).
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Figure 4. Packing diagram in (a) F5BI-PyrTF and (b) F5BI-PyrT2.
Interchanging the donor from (NO2)2BI to F5BI alters the structure and increases XB
interaction strength by nearly 0.7 kcal mol–1 (in both PyrTF- and PyrT2-complexes), even though
the VS,max value of the model F5BI donor is approximately similar to that of (NO2)2BI
(32.9 vs. 33.2 kcal mol–1). In the case of F5BI-PyrTF, XB dimers pack in an orthorhombic pattern
of the P212121 space group (Figure 4a), in which C–I···N is 174.9 °, RI···N is 2.89 Å corresponding
to a %rsvdW of 30.7% (Table 1), and the computed Eint is –6.9 kcal mol–1 (Table S74). The
presence of five -F substituents contributes to the observation of two distinctive -stacking
interactions between the pentafluorobenzene of F5BI and furan moieties of PyrTF at the distances
of 3.75 Å (Eint = –8.0 kcal mol–1) and 4.57 Å (Eint = –5.9 kcal mol–1) (Figure 4a, Figure S14-a,b,
and Table S74).
A decrease in RI···N (0.11 Å) and increase in linearity of C–I···N (3.6°) were observed when
PyrT2 was used in place of PyrTF as the acceptor for co-crystallization. In the monoclinic
assembly of F5BI-PyrT2 whose space group is P21 (Figure 4b), RI···N (2.78 Å) is the shortest XB
distance and its C–I···N (178.5 °) is the closest to linearity when compared to that of the BI
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complexes (Table 1). Moreover, that XB interaction is the strongest (Eint = –7.2 kcal mol–1) among
the BI co-crystals considered here (Table S75). The -stacking interaction between the thiophene
moiety of the acceptor and the benzene ring of the donor exhibits an intermolecular distance of
3.83 Å (Figure 4b) and a computed Eint of –8.1 kcal mol–1 (Table S75). This relatively strong
interaction involves the -cloud of the pyridine moiety and the electronegative belt of the iodine
atom (Figure S15-d).
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Table 2. XB intermolecular separations (RI···N in Å), angles (C–I···N in °), and percent reduction
in the sum of van der Waals radii (%rsvdW)c upon XB formation for the M06-2X/aVDZ model
dimers and the corresponding experimental complexes formed between the XB BAI donors and
acceptors.
Theory
C–I···N
180
180
180
180
180
180
180
Experiment
Complex
RI···N
2.82
2.82
2.86
2.86
2.84
2.84
2.83
2.83
%rsvdW
32.4
RI···N
%rsvdW
33.8-36.0
35.3
C–I···N
(NO2)2BAI-PyrTFc
(NO2)2BAI-PyrT2
F2BAI-PyrTF
2.67-2.76d 174.9 d
32.4
31.4
31.4
31.9
31.9
32.1
32.1
2.70 d
2.78 d
2.76 d
2.75
—
2.71
2.71
0.15
0.11
174.5 d
178.7 d
178.1 d
177.4
—
33.3
33.8
34.1
—
35.0
35.0
3.6
2.5
F2BAI-PyrT2
(CF3)2BAI-PyrTF
(CF3)2BAI-PyrT2
F5BAI-PyrTF
F5BAI-PyrT2
MAD
a
179.0
178.0
5.5
180
AAD
2.8
aX-ray single crystal structure was not obtainable due to fragility of the crystals. Multiple XB
interactions were observed in the experimental co-crystal.43 c Relative to the sum of nitrogen (1.79
Å) and iodine (2.38 Å) van der Waals radii (Table 1).75 dValues previously reported.43
b
Co-crystals of the BAI Series. We now move our attention to the structural characteristics of the
XB BAI complexes. The key geometrical parameters for the BAI series of XB contacts in the
model dimers and experimental co-crystals are reported in Table 2. The single crystal structure of
(CF3)2BAI-PyrT2 could not be obtained due to the fragility of the crystals. In general, the XB
interaction strengths are on the same order of magnitude as those found in the BI co-crystals. With
the exception of PyrTF-(NO2)2BAI,43 the packing patterns observed in the BAI complexes exhibit
a near co-planar arrangement. This affords denser co-crystals with tighter stacking configurations.
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Although the agreement between the theoretically predicted and the experimentally determined
key geometrical parameters is slightly less than in the BI series, they still fall within the error
associated with the level of theory employed here.
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The structural analysis for XB complexes comprised of (NO2)2BAI and F2BAI donors with
both PyrTF and PyrT2 acceptors was reported in our previous study.43 Co-crystals containing
(NO2)2BAI exhibit competing non-covalent interactions, where -stacking between pairs of donor
molecules and donor-acceptor monomers were ~2 kcal/mol stronger than XBs. Exhibiting a
monoclinic structure with a P21/c space group, PyrTF-(NO2)2BAI crystal structure displays high
levels of disordering which are evident by the presence of four distinct XB interactions. By
contrast, PyrT2-(NO2)2BAI gives rise to a more ordered solid-state assembly exhibiting a triclinic
̅
structure with a P1 space group. XB is characterized by an C–I···N of 174.5 and a RI···N of 2.70 Å
with an Eint of –8.7 kcal mol–1. The variations between these two co-crystals are due to the nitro
groups on the XB donor participating in various secondary interactions that act in both stabilizing
(i.e., PyrT2-(NO2)2BAI) and destabilizing (i.e., PyrTF-(NO2)2BAI) manners.43 Co-crystals
containing F2BAI consist of associative XB monomers that participate in nearly co-facial -
interactions. PyrTF-F2BAI (C–I···N of 178.7, RI···N of 2.78 Å, Eint of –7.5 kcal mol–1) exhibits a
monoclinic structure with the P21/c space group where F∙∙∙H interactions contribute to the isotropic
packing behavior of the co-crystal. PyrT2-F2BAI yields crystallization in the triclinic space group
̅
P1 in which XB is characterized by an C–I···N of 178.1 and a RI···N of 2.76 Å with an Eint of –7.6
kcal mol–1.43
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Figure 5. Packing diagram in (CF3)2BAI-PyrTF.
The 1:1 assembly of (CF3)2BAI-PyrTF exhibits a nearly co-planar parallel packing pattern
̅
of the triclinic space group P1 (Figure 5). The two associative monomers form a XB contact with
an C–I···N of 177.4 °, a RI···N of 2.75 Å, corresponding to a %rsvdW of 34.1%, and an Eint of
–7.9 kcal mol–1 (Table S76). The acidic proton attached to the ortho-carbon on the furan moiety
promotes adjacent rows of XB complexes via its interaction with the -orbitals of the acetylene
linker of the donor (3.01 Å, Eint = –0.8 kcal mol–1; Figure S16-c and Table S76). Other
intermolecular contacts also contribute to the packing pattern of the assembly, such as Hthiophene···F
(2.54 Å, Eint = –1.3 kcal mol–1; Figure S16-d and Table S76). In addition, more energetically
competitive parallel displaced -stacking contacts between the two PyrTF acceptors
(4.44 Å, Eint = –8.3 kcal mol–1), and between the donors (4.47 Å, Eint = –5.0 kcal mol–1) are also
observed in the co-crystal (Figure S16-a,b and Table S76).
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Figure 6. Packing diagram in (a) F5BAI-PyrTF and (b) F5BAI-PyrT2.
̅
Similar to that of (CF3)2BAI-PyrTF, the 1:1 assembly of F5BAI-PyrTF exhibits P1 space
group symmetry, in which each XB dimer is anti-parallel to each other (Figure 6a). This
arrangement is in part supported by other favorable interactions such as ortho-Hfuran···C≡C
(2.82 Å, Eint = –2.1 kcal mol–1) and Hthiophene···F (2.39 Å, Eint = –1.4 kcal mol–1)
(Figure S17-c,e and Table S77). XB interactions within this co-crystal are characterized by a RI···N
distance of 2.71 Å associated with a 35.0 %rsvdW, a nearly linear C–I···N of 179 °, and an Eint of
–8.1 kcal mol–1. Competing with the XB contact is the strong parallel displaced -stacking between
the furan moiety of the acceptor and pentafluorobenzene ring of the donor
(3.83 Å, Eint = –8.7 kcal mol–1; Figure S17-a and Table S77).
̅
F5BAI-PyrT2 exhibits a comparable anti-parallel packing pattern of the space group P1
(Figure 6b), in which the donor and the acceptor associate via a XB contact whose RI···N, % rsvdW,

C–I···N, and Eint are 2.71 Å, 35.0%, 178 ° and –8.0 kcal mol–1, respectively. The crystal packing of
F5BAI-PyrT2 is also supported by numerous non-XB pairwise contacts, such as
Hthiophene···π(C≡C) (2.91 Å, Eint = –1.6 kcal mol–1) and Hthiophene···F (2.33 Å, Eint = –1.2
kcal mol–1) (Figure S18-d,e and Table S78). Multiple -stacking interactions (Eint from –5.2 to
–6.5 kcal/mol) are present but weaker than XB contact (Figure S18-a,b,f and Table S78).
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Spectroscopic Analysis of XB Donors and Their Corresponding XB Co-Crystals
Vibrational shifts in various stretching modes, particularly those with distinctive
spectroscopic signatures (e.g., C–H, C–X, C–Y where Y = O, N, S), have been commonly used to
detect the formation of XB interactions.24,36,41,76,77 Although the C≡C stretch has also been used
elsewhere in this context, it is very sensitive to non-XB contacts and can lead to unsystematic
behavior of vibrational frequency shifts. In turn, we30 and others25,26,31,35,38,40,41,45,46,66,78 have taken
an alternative approach involving the interrogation of the C–I stretching mode and their shifts upon
XB formation, as they are far more sensitive to halogen bond formation.79
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Figure 7. Experimental Raman spectra of the region associated with the C–I stretching mode (red
peaks with values directly above) for (a) the BI series and (b) the BAI series of XB donors and
their co-crystals with the acceptors PyrTF and PyrT2.
XB Donors. For the BI series, the computed and experimental C–I stretching frequencies correlate
well to each other with a MAD of 7 cm–1 (F5BI) and an AAD of 4 cm–1 (Table S67). This
agreement facilitates the assignment of C–I stretching modes in the experimental spectra of BI
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donors. The same comparison for the BAI series reveals an agreement between theory and
experiment for F2BAI and F5BAI (3 cm–1 in both cases); however, larger deviations occur for
(CF3)2BAI (13 cm–1) and (NO2)2BAI (17 cm–1) (Table S69). The experimental Raman spectra
shown in the first column of Figure 7a and 7b show a dependence of the C–I stretching frequency
on the properties of donor substituents as well as the hybridization of the carbon atom in the C–I
bond. That is, as the hybridization of the carbon atom of the C–I bond is modified from sp2 to sp,
the frequency of the C–I stretch undergoes a “red shift” (i.e., shift to lower energy). The presence
of electron withdrawing groups also leads to red shifting in the C–I stretching frequency when
compared to the unsubstituted donors (i.e., BI and/or BAI). However, an inconsistent trend
(i.e., does not directly correlate with electron withdrawing ability) in the C–I stretching frequency
(-(NO2)2 > -F2 > -(CF3)2 > -F5) was observed for both BI and BAI series of XB donors. Here, this
irregular behavior is attributed to the vibrational coupling between the C–I stretch and other modes,
such as the in-plane symmetric rocking of -CF3 and -NO2 groups. To test this hypothesis,
vibrational frequencies in a series of para-monosubstituted XB donors (i.e., FBI, CF3BI, and
NO2BI), were computed (Table S70). The results indicate that when such vibrations are not
coupled, as is the case of this para-monosubstituted series, the ordering of the C–I stretching
frequencies does indeed correlate with the electron withdrawing ability of the substituents and the
VS,max of the donors: BI < FBI < CF3BI < NO2BI (see the SI for full detail).
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BI co-crystals. The Raman spectra for the BI co-crystals are reported in Figure 7a. The computed
C–I stretching frequencies for the BI series of model dimers agree well with their experimental
counterparts (MAD = 8 cm–1, AAD = 5 cm–1; Table S68. In addition, their ordering is consistent
with theory; however, it should be noted that only four of the BI series co-crystals were obtainable
(F5BI-PyrR and (NO2)2BI-PyrR, where R is either -TF or -T2). In addition to the shifts in the
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C–I stretching frequency arising from substituent and/or hybridization effects, that frequency is
further red shifted upon XB formation (i.e., complexation shift). These complexation shifts are
commonly rationalized by either charge transfer or the net electrostatic attraction between the non-
bonding electrons of the nitrogen atom and the electropositive -hole of the iodine atom.24,31,78
Both processes tend to weaken the C–I bond through the enhancement of its antibonding character
and in turn, lead to the observed perturbation of its vibrational stretching frequency.
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As seen in the second and third columns of Figure 7a, the C–I stretching frequency of F5BI
in the complexes with either acceptor is lower than that of (NO2)2BI. Through comparing the C–I
stretching frequencies of the XB donors and the XB complexes, a red shift is observed for
F5BI-PyrTF (–4 cm–1) and F5BI-PyrT2 (–11 cm–1). At first glance, these results suggest that the
C–I stretching vibration does depend on the identity of the acceptor. However, armed with the
knowledge regarding the surrounding environment, it becomes clear that the variations between
the complexation shifts of F5BI-PyrTF and F5BI-PyrT2 are due to the dominant non-XB contacts
found in the co-crystals described earlier in this work. This abnormal behavior extends to
(NO2)2BI-PyrTF and (NO2)2BI-PyrT2 as they show somewhat large variations between the
magnitude of their complexation shifts. In fact, in the case of (NO2)2BI-PyrT2, the C–I stretching
frequency actually undergoes a “blue shift” (i.e., shift to higher energy) of +7 cm–1. The
complexation shifts computed between the isolated (NO2)2BI and the corresponding co-crystals
are dissimilar to those computed for the other co-crystals studied in this work. More specifically,
the nitro containing XB donors are the only ones that naturally exist in the solid-state and thus
require the surrounding environment of the (NO2)2BI single crystal be taken into consideration.
The computation of the corresponding complexation shifts involves, like all the other co-crystals
considered here, the C–I stretching frequency of the XB donor. In this particular case, however,
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an intermolecular XB interaction in the isolated (NO2)2BI crystal is detected between the iodine
atom of one XB donor and the oxygen atom of another XB donor (i.e., an I···O XB interaction).80
This observation, in addition to the same vibrational coupling of modes detected in the (NO2)2BI
XB donor, leads to the anomalous behavior seen in the C–I stretching frequency of (NO2)2BI-
PyrTF and (NO2)2BI-PyrT2 co-crystals.
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BAI co-crystals. The Raman spectra for the BAI co-crystals are reported in Figure 7b. Similar to
the XB donors and the BI co-crystals, the theoretical and experimental C–I stretching frequencies
of the BAI co-crystals agree, exhibiting a MAD and AAD of 12 and 6 cm–1, respectively (Table
S70). Additionally, their theoretical and experimental trends with either acceptor are consistent,
albeit unexpected: F5BAI-PyrTF < (CF3)2BAI-PyrTF < F2BAI-PyrTF < (NO2)2BAI-PyrTF
and F5BAI-PyrT2 < F2BAI-PyrT2 < (NO2)2BAI-PyrT2. It should be pointed out that the
variations between BAI co-crystals comprised of PyrTF and/or PyrT2 are smaller (± 2 cm–1) than
those containing BI XB donors (–6 and +9 cm–1 for PyrTF and PyrT2 co-crystals, respectively).
This suggests that in these BAI co-crystals, competitive interactions have far less pronounced
effect on the C–I vibrational signatures.
The vibrational shifts that accompany XB formation in the BAI series of co-crystals,
however, are seemingly “random” ((NO2)2BAI-PyrTF < (CF3)2BAI-PyrTF < F5BAI-PyrTF <
F2BAI-PyrTF and (NO2)2BAI-PyrT2 < F2BAI-PyrT2 < F5BAI-PyrT2) and do not reflect the
order of electron withdrawing ability of the substituents. As discussed above, this unusual trend
performance is in-part a consequence of the vibrational coupling between the C–I stretching and
other vibrational modes. Moreover, the presence of a I···O XB contact in the isolated (NO2)2BAI
(this work; CCDC:1524553) donor crystal, most likely plays a role in the observed trend. Finally,
as conveyed in the structural analysis of the co-crystals, the XB donors in F2BAI-PyrTF, F2BAI-
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PyrT2, and (CF3)2BAI-PyrTF each form homogenous donor-donor interactions in the form of -
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stacking (Eint = –3.7, –4.5, and –5.0 kcal mol–1, respectively). In those donor···donor contacts, the
C–I bond is roughly parallel to and stacked on top of the C≡C bond, much like that of type-II
halogen bonds.22,24 The results from a NBO analysis suggests that the -orbitals around the C≡C
region could perturb the electron density on the C–I bond and in turn, contribute to the unpredicted
trend in the vibrational C–I stretching shifts in these complexes.
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CONCLUSION
In summary, we investigate the substituent, hybridization, and crystal packing effects on the
electronic, structural and spectroscopic properties of two series of XB donors and the 1:1
molecular assemblies formed between them and one of two XB acceptors.
Substituents on the XB donors and the hybridization of the carbon atom in the C–I bond
substantially impact the electronic and structural properties of the co-crystals (e.g., the magnitude
of the -hole, the intermolecular I···N distances, and the interaction strength of XB contacts).
Moreover, strong electron withdrawing substituents (e.g., -NO2 and -F5) also promote
intermolecular π-stacking interactions between the acceptors and donors that are energetically
stronger than the corresponding XB contacts by 0.7-2.4 kcal mol–1. Additionally, the presence of
the triple bond in the BAI donors alters the geometries of XB interactions, resulting in near
co-planar XB contacts, thus stimulating a greater number of competing pair-wise non-XB contacts
than those found in the BI series.
Although the identity of the substituents and the hybridization of the carbon atom in the
C≡C bond undoubtedly influence the vibrational stretching frequency of the C–I bond within XB
complexes, they do not solely govern the vibrational complexation shifts that accompany XB
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formation. In fact, it is vibrational coupling between the C–I stretching and other modes within the
XB donor and the presence of numerous energetically competitive intermolecular interactions
among the donors and acceptors that considerably and unpredictably alter the vibrational
signatures of the corresponding XB co-crystals. The electronic, structural, and vibrational analysis
presented here suggest that the characterization of XBs not only relies on the molecular properties
of the monomers (i.e., XB donor and/or acceptor) but also on the chemical environment
surrounding those XB interactions. As such, it is recommended that a holistic approach, employing
a diverse set of quantitative techniques, should be adopted when attempting to accurately
characterize such interactions in the solid-state.
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ASSOCIATED CONTENT
Supporting Information
Supporting materials contain experimental details regarding crystallographic data, details on
thermal analysis, theoretical calculations, 1H NMR spectra and supplementary results.
Additionally, all crystallographic information files (CIFs) have been attached. This material is
available free of charge via the Internet at http://pubs.acs.org. Crystallographic information files
are also available from the Cambridge Crystallographic Data Center (CCDC) upon request
(http://www.ccdc.cam.ac.uk, CCDC deposition numbers 1590264, 1590265, 1590272-1590276,
and 1502497-1502500).
AUTHOR INFORMATION
Corresponding Authors
*dwatkins@olemiss.edu
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*tschumpr@olemiss.edu
*nhammer@olemiss.edu
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Author Contributions
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‡Suong T. Nguyen, Thomas L. Ellington, and Katelyn E. Allen all contributed equally to this work.
All authors have given approval to the final version of the manuscript.
ACKNOWLEDGMENT
S.T.N and D.L.W. appreciate financial support of this work from the National Science Foundation
CAREER Award under Grant Numbers CHE-1652094. N.I.H. and K.E.A. thank the National
Science Foundation for supporting this work through Grant OIA-1539035. The computational
work is supported by the Mississippi Center for Supercomputing Research and the National
Science Foundation under Grant Numbers OIA-1430364 and CHE-1664998 (T.L.E. and G.S.T.).
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