Multidentate, V-Shaped Pyridine Building Blocks as Tectons for Crystal Engineering

Article abstract of DOI:10.1002/chem.202004918

The formation of supramolecular structural units through self-assembly is a powerful method to design new architectures and materials endowed with specific properties. With the aim of adding a group of versatile tectons to the toolkit of crystal engineers, we have devised and synthesised four new V-shaped building blocks characterised by an aryl acetylene scaffold comprising three substituted pyridine rings connected by two triple bonds. The judicious choice of different substituents on the pyridine rings provides these tectons with distinctive steric, electrostatic and self-assembly properties, which influence their crystal structures and their ability to form co-crystals. Co-crystals of the tectons with tetraiododifluorobenzene were obtained both via traditional and mechanochemical crystallisation strategies, proving their potential use in crystal engineering. The energetic contributions of the supramolecular interactions at play in the crystal lattice have also been evaluated to better understand their nature and strength and to rationalise their role in designing molecular crystals.

Full text of DOI:10.1002/chem.202004918

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
&
Crystal Engineering
Multidentate, V-Shaped Pyridine Building Blocks as Tectons for
Crystal Engineering
Francesca Guagnini, Alessando Pedrini, Enrico Dalcanale, and Chiara Massera*[a]
Abstract: The formation of supramolecular structural units
through self-assembly is a powerful method to design new
architectures and materials endowed with specific proper-
ties. With the aim of adding a group of versatile tectons to
the toolkit of crystal engineers, we have devised and syn-
thesised four new V-shaped building blocks characterised by
an aryl acetylene scaffold comprising three substituted pyri-
dine rings connected by two triple bonds. The judicious
choice of different substituents on the pyridine rings pro-
vides these tectons with distinctive steric, electrostatic and
self-assembly properties, which influence their crystal struc-
tures and their ability to form co-crystals. Co-crystals of the
tectons with tetraiododifluorobenzene were obtained both
via traditional and mechanochemical crystallisation strat-
egies, proving their potential use in crystal engineering. The
energetic contributions of the supramolecular interactions at
play in the crystal lattice have also been evaluated to better
understand their nature and strength and to rationalise their
role in designing molecular crystals.
Introduction
columnar arrangement in the solid state. Despite the lack of
pores, the material can take up guests such as trifluoroethanol,
I2, H2 or CO2.[16,17] Furthermore, the columnar assemblies have
been shown to adsorb and organise small guest molecules
that interact via H-bonds.[18] The same group reported the
preparation of a wider bis-urea macrocycle, based on a pyridyl-
acetylene scaffold, capable of acting as nanoreactor for the
polymerisation of isoprene.[19] Johnson and co-workers syn-
thesised a library of inherently fluorescent pyridine-based urea
receptors that were successfully employed in the sensing of
ClÀ and other anions.[20–25] The same group has recently report-
ed a 3,5-bis((2-iodophenyl)ethynyl)pyridinium scaffold function-
alised with a methanesulfonyl withdrawing group to polarise
iodine halogen bonding units for anion binding.[26] Similarly,
Berryman and co-workers suggested a possible strategy to
pre-organise pyridine-acetylene receptors via intramolecular
hydrogen bond-halogen bonds (HB-XB).[27] The resulting planar
receptor showed a ninefold increase in binding to halides (IÀ
and BrÀ). Against this background, and with the aim of adding
a group of versatile tectons to the toolkit of crystal engi-
neers,[28] we designed and synthesised four new V-shaped mul-
tidentate building blocks characterised by an aryl acetylene
scaffold comprising three substituted pyridine rings connected
by two triple bonds (Figure 1, left). The substituents on the
two lateral pyridine rings— namely Br atoms (TBr), carboxylic
groups (TA), triple bonds (TT) and amine groups (TN)— were
chosen to endow the tectons with different steric, electrostatic
(Figure 1, right) and self-assembly properties, so as to system-
atically study the differences in their resulting crystal struc-
tures. Moreover, in the solid state, the free rotation of the pyri-
dine rings around the triple bonds allows the tectons to adopt
three different conformations (C, S or W, respectively; Figure 1)
depending on the relative orientation of the pyridyl rings.
Self-assembly is one of the key strategies to generate sophisti-
cated architectures, from discrete cages to 3D networks.[1] Mo-
lecular tectons endowed with functionalities suitable for both
metal coordination and weak interactions are interesting build-
ing blocks for generating new materials with desired proper-
ties.[2] In this context, multidentate tectons bearing pyridine
groups are extremely versatile. Pyridines can interact with
metals but are also excellent hydrogen- and halogen-bond ac-
ceptors. In addition, their aromaticity promotes p-p stacking,
CÀH···p and CÀF···p interactions. Several studies have been re-
ported in which multipyridine-based tectons have been used
to develop metallocycles and cages that can be tuned and
controlled by design and chemical stimuli.[3–13] These systems
have been extensively investigated for drug delivery[10–12] and
catalysis.[13] Some examples of shape-persistent cyclic tectons
bearing pyridine moieties have recently been reported and
studied for their self-assembly or recognition properties[14]
based on their intrinsic porosity.[15] Extrinsic porosity, in which
the cavities are located between the molecules by the inter-
play of different intermolecular interactions, is another efficient
method to obtain materials to be used for separation, catalysis
or storage. By following this strategy, the Shimizu group has
synthesised a pyridyl-bis-urea macrocycle assembling into a
[a] Dr. F. Guagnini, Dr. A. Pedrini, Prof. E. Dalcanale, Prof. C. Massera
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità
Ambientale and INSTM UdR Parma, Università di Parma
Parco Area delle Scienze 17/A, 43123 Parma (PR) (Italy)
E-mail: chiara.massera@unipr.it
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
https://doi.org/10.1002/chem.202004918.
Chem. Eur. J. 2021, 27, 4660 –4669
4660
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
Figure 1. Left: Molecular sketch of the different conformations that the pyridine-based tectons (TBr, TA, TT and TN) can adopt by rotation around the acety-
lene bonds. Right: Molecular electrostatic potential surfaces for TBr, TA, TT and TN calculated at the B3LYP/6–311++G(d,p) level of theory using Gaussian 09
starting from the geometry present in their crystal structures.[30] The colour code from red to blue indicate areas of rich (hydrogen/halogen-bond acceptor
sites) and depleted (hydrogen-bond donor sites) electron density, respectively.
To test the behaviour of the tectons as halogen-bond ac-
ceptors, and to study how this would affect their self-assembly,
we co-crystallised them with 1,4-diiodotetrafluorobenzene
(DITFB), which has been widely used in crystal engineering for
its ability to form N···I halogen bonds.[29] The halogen bond is
an interaction occurring between an electrophilic region
(called s-hole) associated with a halogen atom (the halogen-
bond donor) and a nucleophilic region (the halogen-bond ac-
Scheme 1. Retrosynthesis for TBr, TA, TT and TN. The first disconnection
ceptor).[31] Thanks to its directionality, it has been widely used
leads to synthons for Sonogashira coupling. The functional group for the
coupling, halogen and triple bond, can be either on the axial or the central
over the past 20 years in the field of supramolecular chemistry
for designing molecular crystals.[29c,32] Halogen- and hydrogen-
bonding often compete in determining the outcome of supra-
molecular structures, giving rise to a plethora of different net-
works depending on the molecular geometries and the num-
bers and strength of the donors and acceptors involved.[1e]
Given the chemical nature of the tecton objects of the present
study, the interplay between halogen- and hydrogen-bonding
in directing the final solid-state structure was of particular in-
terest. Single crystals suitable for X-ray diffraction were ob-
tained for TBr, TN and TA, for which it was thus possible to an-
alyse in detail the solid-state assembly. Crystals of TT were ob-
tained only in combination with DITFB and will therefore be
discussed in the relevant section.
pyridine. Both options were tested. The combination giving the highest
yield was used in the final syntheses.
Self-assembly of the tectons: The role of solvent and
substituents
Scheme 2 highlights the sites of the V-shaped building blocks
that can trigger the formation of supramolecular interactions
(in particular hydrogen-bond, halogen-bond, or p–p stacking),
along with a summary of the interactions at work in the crystal
structures of TBr, TN and TA.
As bromine attached to a pyridine ring is a relative weak hal-
ogen bond donor, it is to be expected that hydrogen bonds
and p–p stacking are the driving force in the crystal packing of
the tectons.
Results and Discussion
Crystal structures of TBr
Synthesis of the tectons
Crystals of TBr (which does not possess any strong H-bond
donors) were grown by slow evaporation of different solvents,
namely toluene, benzene, chloroform and methanol. The first
three solvents were not included in the final structure, but
they nevertheless influenced the polymorphic forms obtained,
indicated as TBrT, TBrB and TBrC, respectively. Crystallisation
from methanol led to a solvated form, TBrM.
In the molecular structure of TBrT, the tecton adopts a C
conformation (Figure 1, Figure 2A). The angles between the
mean planes passing through the central ring (acetylene moi-
eties included) and the two lateral pyridine fragments C8-C12/
N2/Br1 and C15-C19/N3/Br2 are 55.85(6)8 and 50.78(4)8, respec-
The tectons TBr, TA, TT and TN were obtained by following
the retrosynthetic strategy shown in Scheme 1 (see the Sup-
porting Information for a detailed discussion of the synthetic
procedure). The disconnection of the triple bonds leads to pyr-
idinic synthons. Functionalisation can be achieved by changing
the substituents on the starting pyridine. The tert-butoxy
group in the para-position on the central ring was selected to
ensure solubility in most organic solvents.
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4661
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
Figure 2. A) Molecular structure of TBrT with partial labelling Scheme. B) Rel-
evant weak interactions in TBrT. Symmetry codes: i=1+x, 1/2Ày, À1/2+z;
ii=x-1, y, z. C) Packing in the crystal structure of TBrT. H atoms have been
omitted for clarity.
Scheme 2. Top: Sites involved in the formation of supramolecular interac-
tions in TBr, TN, TA. Bottom: summary of the main supramolecular interac-
tions at play in the crystal structures of TBr, TN and TA (see discussion
below).
tively. These lateral pyridine fragments are at an 87.99(6)8
angle with respect to each other. In the crystal structure, the
TBr molecules pack through a series of CÀH···N and p–p stack-
ing interactions (Figure 2B). More precisely, each TBr acts both
as donor and acceptor towards a symmetry-related molecule ii
(ii=xÀ1, y, z), forming four distinct interactions [C11ÀH11···N2,
3.328(5) Š and 170.78(2)8; C12ÀH12···N1, 3.534(4) Š and
As can be qualitatively seen in Figure 1, the depleted elec-
tron density areas (hydrogen-bond donor sites) in TBr are lo-
cated around the H atoms of the aromatic rings and the tert-
butyl groups. Indeed, analysis of the crystal structure of TBrT
highlighted the tendency of the pyridyl moieties to act as H-
bond acceptors towards the aromatic CÀH groups (Figure 2B).
Therefore, we decided to use benzene as crystallisation sol-
149.70(4)8; C18ÀH18···N3, 3.324(2) Š and 167.74(8)8; C19À vent, which could possibly template the crystal packing of TBr,
H19···N1, 3.508(4) Š and 155.92(8)8]. On the other side, p–p
stacking is present between the pyridine rings C15ÀC19/N3/
Br2 and C8ÀC12/N2/Br1 (in position 1+x, 1/2Ày, À1/2+z).
The main geometrical parameters are the two distances cen-
troid···C8 of 3.526(5) Š and centroid···C15 of 3.529(6) Š.
These sets of interactions contribute to the overall packing
of the molecule, which is very compact without accessible
voids (Figure 2C). The synergistic effect of stacking and non-
conventional H-bonding interactions seems to dominate over
the formation of Br···N halogen bonding or Br···Br contacts of
type I/II.[33]
being less sterically hindered than toluene. When crystals
grown from benzene were analysed, no solvent appeared to
be included, but a different polymorph of TBr was obtained
(TBrB). In this case, the conformation of TBr turned out to be
of the S type (Figure 1, Figure 3A) with the pyridine ring con-
taining the nitrogen atom N3 pointing upwards with respect
to N1 and N2. In TBrB, the molecules are more planar than in
the previous case, as can be seen from the angles formed by
the mean planes passing through the rings [43.11(7)8, 13.42(7)8
and 33.16(8)8, following the description given for TBrT]. This
different conformation is clearly connected with the overall
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4662
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
Figure 3 for clarity; the distance of the mean planes passing
through the rings in position x, y, z and Àx, 2Ày, 1Àz is
3.412(3) Š]. Also in this case, the final packing is extremely
compact without any accessible permanent porosity (Fig-
ure 3C).
A third batch of crystals was grown from chloroform, yield-
ing again the tecton in a C conformation (TBrC, Figure S36 A).
The TBrC molecular structure is almost perfectly superimposa-
ble with that of TBrT grown from toluene. However, in the
chloroform case, the molecule crystallises in the triclinic space
¯
group P1 as opposed to the monoclinic P21/c of TBrT, leading
to some minor differences in the crystal packing (Figure S36 B).
In all three of the polymorphic forms (TBrT, TBrB and TBrC),
the bromine atoms do not play an active role in the formation
of supramolecular interactions. Their only influence on the
packing is due to their steric hindrance.
In our crystallisation experiments, the only solvent that was
included in the final structure was methanol, a “non-innocent”
molecule capable of interacting via H-bonds, which yielded the
solvated form TBrM with a 1:1 tecton/solvent ratio (Figure 4A).
The conformation of the tecton is S, as in the case of TBrB.
The pyridine ring C8-C12/N2/Br1, which points upward with
respect to the other two pyridine moieties, is held in place by
a O1S-H1O···N2 H-bond [2.975(3) Š, 171.23(6)8]. Besides this in-
teraction, methanol plays no other role in the final crystal
Figure 3. A) Molecular structure of TBrB with partial labelling Scheme. B) Rel-
evant weak interactions in TBrB. Symmetry codes: i=2Àx, 1Ày, 1Àz;
ii=1Àx, 1Ày, Àz; iii=x-1, y, z. C) Packing in the crystal structure of TBrB. H
atoms have been omitted for clarity.
crystal structure and the set of supramolecular interactions
consolidating it (Figure 3B).
In this case, each TBr molecule forms two sets of centrosym-
metric CÀH···N interactions with two other molecules in posi-
tion i=2Àx, 1Ày, 1Àz and ii=1Àx, 1Ày, Àz, of the type C23À
H23B···N3 [3.387(5) Š and 134.34(8)8] and C18ÀH18···N1
[3.492(4) Š and 157.58(7)8] with the tert-butyl CÀH atoms as H-
bond donors. A short p–p interaction is also present, involving
the p cloud of one triple bond and the C15ÀC19/N3/Br2 ring
of a TBr tecton in position iii=xÀ1, y, z [centroid···C13,
3.696(3) Š]. Finally, p–p interactions are present involving the
pyridine rings N2/C8ÀC12 of adjacent molecules [not shown in
Figure 4. A) Molecular structure of TBrM, highlighting the H-bond (blue
dashed line) between one pyridine ring and the methanol molecule. B) Main
weak interactions contributing to the overall general packing of TBrM:
a) centroid···centroid interactions between pyridine rings. b) CÀH···N and CÀ
H···O interactions. c) CÀH···ptriplebond interactions.
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4663
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
packing, again featuring p–p and CÀH···N interactions (Fig-
ure 4B). In particular, Figure 4Ba shows the weak p–p stacking
involving the pyridine rings C8ÀC12/N1/Br1 and C15-C19/N2/
Br2 in position x, 1Ày, 1/2+z [3.804(5) Š]. Furthermore, each
TBr forms a supramolecular dimer held together by CÀH···N in-
teractions [C11ÀH11···N1(3/2Àx, 3/2Ày, 1Àz), 3.434(2) Š and
144.03(2)8; C10-H10···N3(3/2Àx, 3/2Ày, 1Àz), 3.506(4) Š and
152.66(7)8] (Figure 4Bb). Supramolecular dimers assemble in
As shown in Figure 5A, each of the -NH2 groups and of the
pyridine rings act as H-bond donor and acceptor, respectively,
with two adjacent molecules, thus forming a chain along the
c-axis direction [N3-H3NB···N1, 3.301(3) Š and 152.08(8)8; N3-
H3NA···N2, 3.085(2) Š and 173.39(7)8; N5-H5NA···N1, 3.474(4) Š
and 148.64(5)8; N5-H5NB···N4, 3.123(4) Š and 171.89(7)8]. The
crystal structure is further consolidated by weak p-p stacking
interactions involving the side pyridine rings [the cen-
tetramers formed by two sets of weak centrosymmetric CÀ troid(blue)···centroid(red) distance is of 3.751(9) Š]. The overall
H···O hydrogen bonds [C21-H21B···O1(1Àx, Ày, 1Àz), 3.619(4) Š
and 158.01(4)8]. The tetramers assemble in a layer parallel to
the (101) plane. In addition, a supramolecular dimer is also
formed by the interaction of a CÀH group from the pyridine
molecule C15ÀC19/N2/Br2 and the electronic p cloud of the
triple bond [C19-H19···C7(3/2Àx, 1/2Ày, 1Àz), 3.646(4) Š and
145.82(8)8] (Figure 4Bc).
crystal packing of TN consists of sets of H-bonded chains held
together by van der Waals forces. As could be expected based
on the functional groups present, the structure shows a very
efficient occupancy of space with no accessible voids (Fig-
ure 5B).
Crystal structure of TA
The main feature of TA is the presence of two carboxylic
groups, which are very effective H-bonding donor/acceptors
moieties, with the C=O and the CÀOH fragments displaying a
negative and a positive region of electron density, respectively
(Figure 1). Concomitantly, TA possesses very good H-bond ac-
ceptors: the nitrogen atoms of the pyridine rings. In theory,
this tecton could assemble in supramolecular polymers
through centrosymmetric dimeric O2-H2O···O3 and O4-
H4O···O5 H-bonds or possibly create a macrocycle (Scheme S7),
Crystal structure of TN
Crystals of TN were obtained by slow evaporation of a chloro-
form solution. In this case, solvents capable of forming H-
bonds were excluded, to avoid any influence on the packing
of the ligand. TN is characterized by the presence of -NH2 sub-
stituents on the lateral pyridine rings (characterised by a deple-
tion of electron density, Figure 1) which are good H-donor
moieties, and of the pyridyl fragments, which are good hydro-
gen-bond acceptors.
via the well-known R2 (8) supramolecular homosynthon
2
Hence, the main interaction directing the final crystal pack-
{···HOC=O}2. A dimeric species was indeed observed in the gas
phase via ESI-MS spectrometry (Figure S15). However, crystals
of TA were only obtained by slow evaporation of an acetone
solution, which resulted in a monohydrate form [Figure 6A;
O2ÀH2O···O1W, 2.600(2) Š and 173.88(4)8]. The dimeric H-
bonded motif between the carboxylic acids of the pyridine
ing is H-bond with the formation of classic R2 (8) [and also
2
R2 (18)] synthons typical of aminopyridine groups (Figure 5A).
2
Figure 5. A) Molecular structure of TN showing the H-bonding motif con-
necting TN molecules along the c-axis direction. The molecules b and c are
in positions 2Àx, Ày, Àz and 2Àx, Ày, 1Àz, respectively. The centroids of the
pyridine rings are indicated as blue and red spheres. B) Packing of TN show-
ing the reciprocal position of sets of H-bonded chains (highlighted in green,
magenta, blue and orange), held together by van der Waals interactions.
Figure 6. A) Molecular structure of the monohydrate form of TA, highlight-
ing the H-bond (blue dashed line) between the carboxylic acid of the pyri-
dine ring and the water lattice molecule. B) View of the relevant interactions
(shown as dotted lines) in the crystal structure of TA. One of the supra-
molecular chains is highlighted in blue. The chains form a layer parallel to
(111) through H-bonds with the lattice water molecules.
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4664
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
rings does not take place because of the lattice water mole-
cule, but TA still forms H-bonded supramolecular chains C(18)
(highlighted in blue in Figure 6B), based on the C=O···HÀO
synthon.
More precisely, the carboxylic oxygen atom O3 of one TA
acts as hydrogen-bond acceptor towards the O4-H4O fragment
of an adjacent molecule in position x, À1+y, 1+z, while the
C=O5 moiety remains free [O4ÀH4A···O3, 2.694(2) Š and
164.36(4)8]. These chains are further bridged to form undulat-
ed layers parallel to the plane (111), with each water molecule
acting as acceptor towards the O2-H2O group [O2ÀH2A···O1W,
2.600(2) Š and 173.88(4)8], and as donor towards the pyridine
rings [O1WÀH1W···N1(x, À1+y, z), 2.968(3) Š and 149.70(6)8].
Finally, different layers are connected through van der Waals
interactions, p–p
stacking
and H-bonding [O1WÀ
H2W···N2(1Àx, Ày, 1Àz), 2.926(5) Š and 165.57(4)8] to yield a
compact structure without voids.
Co-crystallisation with DITFB
The systematic analysis of the crystal structures of the tectons
showed their marked tendency to form tightly packed net-
works. As argued by Kitaigorodskii in his studies on organic
crystals, molecules assemble to minimise free space.[34] In our
case, the assembly was driven by both hydrogen bonding and
p–p stacking interactions, as expected. Furthermore, we ob-
served a strong influence of the different functional groups on
the pyridine rings and of the crystallisation solvents. Introduc-
ing DITFB to form a set of co-crystals was therefore a way to
induce the formation of new networks exploiting the competi-
tion between halogen- and hydrogen-bonds with the pyridine
rings.
Figure 7. A) Molecular structure of the co-crystal formed by TBr and DFTIB.
B) Packing of the co-crystal TBr-DITFB, showing two supramolecular chains
formed by Br···Br interactions (orange dotted lines) propagating in two dif-
ferent directions. The chains are bridged by DFTIB molecules through halo-
gen bonds (blue dotted lines). H atoms have been omitted for clarity.
C) Centrosymmetric dimers formed by p–p stacking involving the aromatic
rings of TBr and of DITFB. D) Crystal packing of TBr-DITFB viewed along the
b-axis direction highlighting the voids as yellow cylinders.
As preliminary investigation, the crystallisation experiments
were performed in a 2:1 tecton/DITFB molar ratio, to favour
the assembly of the tecton around iodofluorobenzene. We car-
ried out two types of crystallisation. The first type consisted of
a “classic” method; namely, slow evaporation of a saturated so-
lution. The second experiment comprised a liquid-assisted
grinding (LAG) step, followed by re-crystallisation in chloro-
form, thus using the grinded powder as crystallisation seed[35]
(see the Supporting Information for experimental details). Sev-
eral attempts of growing co-crystals of TA and DITFB both
from solution and from grinding always yielded crystals of the
two components alone, most likely because of the important
role of H-bonding in directing the crystallisation of TA. In the
case of TN, it was possible to obtain co-crystals with DITFB
only by employing the LAG step, suggesting the potential of
this technique.
cules in a chain. In the crystal, two sets of these chains are
formed, oriented along different planes of the cell, that propa-
gate at an angle of roughly 698 one with respect to the other.
The chains are held together by DITFB molecules that bridge
pairs of TBr tectons in a zig-zag fashion through halogen
bonds I1···N1 [3.009(3) Š] and I2···N3(x, 3/2Ày, 1/2+z)
[3.058(3) Š] (Figure 7B). One halogen bond involves the central
pyridine, the second is formed with one of the two lateral pyri-
dine rings (Figure 7B), while the N atom of the third ring does
not form any interaction.
In addition, centrosymmetric supramolecular dimers are
formed by mutual p–p stacking of the lateral pyridine moieties
[Cg1···Cg2i, 3.536(8) Š] and by the weak interaction of DITFB
with the central ring of TBr [Cg3···Cg4i, 3.536(8) Š] (Figure 7C;
symmetry code i=1Àx, 1Ày, 1Àz).
Co-crystal TBr-DITFB
In the case of TBr, both methods yielded the same 1:1 co-crys-
tal (Figure 7A). In the asymmetric unit, the nitrogen atom N1
of the central pyridine ring is halogen bonded to the iodine
atom I1 of DITFB [I1···N1, 3.009(3) Š] (Figure 7A). TBr adopts a
W conformation (Figure 1), which is consolidated by a series of
type II Br···Br interactions at 3.574(6) Š connecting the mole-
It is also possible to analyse the topology of the interactions
present in the crystal structure of TBr-DITFB by means of the
software ToposPro.[36] In particular, the structure can be simpli-
fied to its standard representation by considering the centroids
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4665
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
of the molecules TBr and DITFB as the nodes of the simplified
net, connected through the halogen bonds N···I and Br···Br
mentioned above. Successively, the final underlying net is ob-
tained by deleting the 2-coordinated nodes represented by
the bridging DITFB molecules, to yield a 4-c, cds net {65.8}
with vertex symbol [6.6.6.6.6(2).*][37] (see Figure S56 B). Accord-
ing to this analysis, in the structure there are four interpene-
trating nets (see Figure S56 C) related both by translation and
inversion, belonging to the Class IIIa.[38]
Due to the interactions described above, the co-crystal as-
sembles in a set of channels, parallel to the b-axis direction,
which are filled with chloroform molecules (Figure 7D). The
highly disordered solvent could not be sensibly modelled and
was treated with the program SQUEEZE (see experimental sec-
tion). In contrast to the tightly packed arrangements of the
tecton alone, the overall structure shows ca. 23% of voids in
the unit cell (as calculated by the program PLATON with a
probe radius of 1.2 Š).[39] This structure could potentially dis-
play an extrinsic porosity if its permeability without structural
collapse/modification due to the removal of the solvent were
to be demonstrated.[40]
Co-crystal TN-DITFB
Tecton TN offered the possibility of analysing the effect (either
orthogonal or competing) of concomitant strong hydrogen
and halogen bonding interactions. The co-crystal between TN
and DITFB was obtained only through grinding, since the crys-
tals grown from slow evaporation of a solution of the two
components turned out to be the two starting compounds.
The asymmetric unit of TN-DITFB consists of a TN tecton in W
conformation, two DFTIB molecules and adventitious water.
The pyridine ring containing atoms N2 and N3 was found to
be disordered over two positions, as was the water lattice mol-
ecule O1W. Figure 8A shows all the relevant supramolecular in-
teractions that a molecule of TN in general position forms with
symmetry-related water, TN and DITFB molecules through hy-
drogen (of medium to weak strength) and halogen bonds, re-
spectively. [O1WA···N2A, 2.717(2) Š; O1WAi···N3A, 2.930(2) Š;
N5ÀH5N2···N5iii and N5ivÀH5N2iv···N5, 3.574(3) Š and 136.10(9)8;
N1···I2B, 2.948(6) Š; N4···I2A, 2.966 Š; for symmetry codes see
Figure 8A]. Different to what was observed in the crystal struc-
ture of TN, the amino moieties are involved in H-bonds either
with each other or with water. Two of the pyridine rings act as
halogen-bond acceptors, whilst the third interacts with water.
One of the main features of the crystal packing is the presence
of channels along the c-axis direction (Figure 8B). Such chan-
nels are centred around the sixfold axis of the hexagonal
space group P64 in which the co-crystal crystallises. However,
the channels are very small (3% of the unit cell volume calcu-
lated with a probe radius of 1.2 Š by the program PLATON)[39]
and they are occupied by some residual electron density
found at 1.9–2.2 Š from O1W that can be ascribed to some fur-
ther, unmodelled disorder of the water molecule.
Figure 8. A) View of the ligand TN forming supramolecular interactions with
symmetry-related neighbouring molecules. Symmetry codes: i=xÀy, x, 2/
3+z; ii=Àx+y, 1Ày, 5/3+z; iii=Àx+y, 1Àx, À1/3+z; iv=1Ày, 1Àx+y, 1/
3+z. Only the H atoms of the amino groups are shown. B) Packing of TN-
DITFB viewed along the c-axis direction. Water molecules and H atoms have
been omitted for clarity. The channels are represented as yellow cylinders.
Co-crystal TT-DITFB
We then analysed the behaviour of the trimer TT, bearing
triple bonds as substituents on the lateral pyridine rings (Fig-
ure 9A). In this case, the crystals were obtained directly from
solution, but not from the grinding experiment. The asymmet-
ric unit of the co-crystal comprises one TT molecule in a W
conformation and two DITFB molecules. In the absence of sub-
stituents suitable for hydrogen bonding or adventitious water
molecules, all the three pyridine rings are simultaneously in-
volved in halogen bonds with DITFB molecules [I1Ai···N1,
2.951(2) Š; I2A···N2, 2.942(2) Š; I2B···N3, 3.029(4) Š; for the sym-
metry code see Figure 9A]. The resulting 1:3 assembly is
roughly planar, (Figure 9A); planarity is maintained in the crys-
tal structure, which consists of layers parallel to the (À101)
plane, consolidated by a series of weak CÀH···F interactions in-
volving both the C14-H14 acetylene moiety and the tert-butyl
group [Figure 9B; F1B···H14ÀC14(1+x, y, 1+z), 2.62 Š,
3.181(3) Š and 118.30(7)8; C27ÀH27A···F4B, 2.66 Š, 3.576(4) Š
and 155.67(8)8]. In this case, the packing does not show the
presence of accessible voids, and no solvent is included. In the
absence of bulky Br substituents or of moieties capable of
forming strong H-bonds (such as the carboxylic acid or amino
groups), the DITFB molecule can assemble around itself three
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4666
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
Figure 10. Stick (left) and space filling (right) assembly of TT molecules
around a central DITFB.
observed in the structure of the tectons alone, paving the way
for the possible formation of porous networks.
Interaction energy calculations
To better understand the supramolecular forces at play in the
crystal structures described so far, we calculated the intermo-
lecular interaction energies and visualised them through
[41]
“energy frameworks” using the program CrystalExplorer17.[42]
In this approach, which goes beyond the focus on specific
atom-atom contacts, the total interaction energies (Etot) are cal-
culated starting from the crystal geometry using either a CE-
B3LYP/6-31G(d,p) or a HF/3–21G level of theory. The total
energy comprises four components; namely, the electrostatic
(Eele), polarisation (Epol), dispersion (Edis) and exchange-repulsion
(Erep) terms, which are also given as output of the calculation.
Once the energies have been determined, they can be
graphically displayed in the form of frameworks, which are vi-
sualised as cylinders joining the centres of mass of the mole-
cules in the crystal, with the cylinder radius proportional to the
magnitude of the interaction energy in different directions.[41b,d]
Energy frameworks highlight the topology of the interaction
energies between molecular pairs, and how particular contacts
contribute to the crystal lattice energy. This approach can be
extremely useful, for instance, when comparing polymorphs,
thus providing a valuable tool to summarise qualitatively and
quantitatively the strength of the interactions involved in the
formation of the crystal structures. Details of the interaction
energy frameworks obtained for the different tectons are re-
ported in Section 4 of the Supporting Information. In summary,
this investigation shows that, in the case of the TBr family, the
most important contribution comes from dispersion interac-
Figure 9. A) View of the halogen bonds formed in the crystal structure of
TT-DITFB. The molecule labelled i is in special position (i=x, 1+y, z).
B) Packing of TT-DITFB showing layers parallel to the (À101) plane and
detail of the weak CÀH···F interactions.
different TT tectons (one slightly off-set) by the synergistic
effect of N···I and CÀH···F interactions (Figure 10).
Scheme 3 summarises the most important features of the
three co-crystals obtained. In general, the combination with
DITFB shows a disruption of the compact crystalline packing
Scheme 3. Schematic view of the main features in the crystal structures of DITFB with TBr, TN and TT.
Chem. Eur. J. 2021, 27, 4660 –4669 www.chemeurj.org
4667
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
tions and particularly from p–p stacking, especially in the poly-
morph grown from benzene. For this reason, compact pack-
ings without accessible voids were observed with all the crys-
tallisation solvents employed. Substitution of the bromine
atom with the amino group or the carboxylic acid in TN and
TA leads to an increase of the electrostatic contribution and a
dominant role of hydrogen bonding. Especially in the case of
TA, this leads to a higher complexity in the resulting tridimen-
sional network.
Acknowledgements
Part of this article is based on results described in the PhD
thesis of Francesca Guagnini.[43] Financial support was provided
by University of Parma intramural funding (PhD fellowship to
F.G.). This work has also benefited from the equipment and
framework of the COMP-HUB initiative, funded by the “Depart-
ments of Excellence” program of the Italian Ministry for Educa-
tion, University and Research (MIUR, 2018-2022). D. Acquotti
and S. Ghelli (CIM, Unipr) are thanked for assistance with NMR
spectroscopy. We would also like to acknowledge Dr. Stefano
Canossa for TBrT structure data collection and for advice on
crystal growth. C.M. wishes to thank Professor Alessia Bacchi
for fruitful discussion on the energetic analysis of supramolec-
ular interactions in crystals.
In the case of the co-crystals with DITFB, which is itself an
aromatic compound, p–p stacking is still a dominant interac-
tion when TBr is employed. On the other hand, the energetic
contribution of halogen bonding clearly increases in the co-
crystals of TT and TN, the crystal structures of which are the
result of a synergistic effect between the two types of interac-
tions.
Conflict of interest
Conclusions
The authors declare no conflict of interest.
In this contribution, we have presented the synthesis and
structural characterisation of four new multidentate pyridine-
based building blocks as tectons for crystal engineering. These
tectons possess a rigid, V-shaped aromatic scaffold comprising
a pyridyl-acetylene system functionalised with different moiet-
ies that influence their solid-state assemblies. Their crystal
structures are mainly driven by H-bonds, CÀH···p and p–p in-
teractions, with a preference towards the formation of tightly
packed architectures (especially in the case of the bromine de-
rivatives), that can be highly influenced by the presence of sol-
vent in the lattice. The three pyridine rings in the V-shape ar-
rangement make the tectons good halogen-bond acceptors, as
shown by the co-crystallisation experiments with DITFB, and
can be exploited to modify the crystal structures by forming
potentially porous adducts, as in the case of TBr-DITFB. Identi-
fying and evaluating the energetic contributions of supra-
molecular interactions to lattice energies is important to ex-
tract some design principles from similar and related crystal
structures. Thus, we have calculated the intermolecular interac-
tion energies and visualised them by means of the related
energy frameworks. Due to the presence of three aromatic
rings and two triple bonds, dispersion interactions are always
to be reckoned with and favour the formation of layered struc-
tures. We think that these newly synthesised molecules can
open several opportunities to obtain new materials endowed
with specific properties, besides adding a piece to the puzzle
of the empirically derived principles for the design of molecu-
lar crystals.
Keywords: crystal engineering · ligand design · noncovalent
interactions · self-assembly · supramolecular chemistry
[1] a) Current Challenges on Large Supramolecular Assemblies (Ed.: G. Tsou-
caris), Springer, Dordrecht, 2012; b) J.-M. Lehn, Science 2002, 295,
2400–2403; c) Supramolecular Science: Where It Is and Where It Is Going
(Ed.: R. Ungaro, E. Dalcanale), Springer, Dordrecht, 1999; d) G. M. White-
sides, M. Boncheva, Proc. Natl. Acad. Sci. USA 2002, 99, 4769–4774;
e) F. M. Menger, Proc. Natl. Acad. Sci. USA 2002, 99, 4818–4822; f) M. K.
Corpinot, D.-K. Bucar, Cryst. Growth Des. 2019, 19, 1426–1453.
[2] a) W. T. S. Huck, R. Hulst, P. Timmerman, F. C. J. M. van Veggel, D. N. Rein-
houdt, Angew. Chem. Int. Ed. Engl. 1997, 36, 1006–1008; Angew. Chem.
1997, 109, 1046–1049; b) C.-H. Wong, CÀH, S. C. Zimmerman, Chem.
Commun. 2013, 49, 1679–1695; c) M. L. Saha, S. De, S. Pramanik, M.
Schmittel, Chem. Soc. Rev. 2013, 42, 6860–6909.
[3] P. Liao, B. W. Langloss, A. M. Johnson, E. R. Knudsen, F. S. Tham, R. R.
Julian, R. J. Hooley, Chem. Commun. 2010, 46, 4932–4934.
[4] K. J. Kilpin, M. L. Gower, S. G. Telfer, G. B. Jameson, J. D. Crowley, Inorg.
Chem. 2011, 50, 1123–1134.
[5] C. Gütz, R. Hovorka, G. Schnakenburg, A. Lützen, Chem. Eur. J. 2013, 19,
10890–10894.
[6] D. P. August, G. S. Nichol, P. J. Lusby, Angew. Chem. Int. Ed. 2016, 55,
15022–15026; Angew. Chem. 2016, 128, 15246–15250.
[7] L. Wang, Z. Zhang, X. Jiang, J. A. Irvin, C. Liu, M. Wang, X. Li, Inorg.
Chem. 2018, 57, 3548–3558.
[8] J. R. Li, A. A. Yakovenko, W. Lu, D. J. Timmons, W. Zhuang, D. Yuan, H. C.
Zhou, J. Am. Chem. Soc. 2010, 132, 17599–17610.
[9] a) D. Preston, S. M. McNeill, J. E. M. Lewis, G. I. Giles, J. D. Crowley, Dalt.
Trans. 2016, 45, 8050; b) J. E. M. Lewis, A. Tarzia, A. J. P. White, K. E. Jelfs,
Chem. Sci. 2020, 11, 677–683; c) E. Puig, C. Desmarets, G. Gontard,
M. N. Rager, A. L. Cooksy, H. Amouri, Inorg. Chem. 2019, 58, 3189–3195;
d) S. Bhowmick, S. Chakraborty, S. R. Marri, J. N. Beherab, N. Das, RSC
Adv. 2016, 6, 8992–9001.
[10] F. Kaiser, A. Schmidt, W. Heydenreuter, P. J. Altmann, A. Casini, S. A.
Sieber, F. E. Kuehn, Eur. J. Inorg. Chem. 2016, 5189–5196.
[11] A. Schmidt, V. Molano, M. Hollering, A. Pçthig, A. Casini, F. E. Kühn,
Chem. Eur. J. 2016, 22, 2253–2256.
Experimental Section
[12] J. Han, A. Schmidt, T. Zhang, H. Permentier, G. M. M. Groothuis, R. Bis-
choff, F. E. Kühn, P. Horvatovich, A. Casini, Chem. Commun. 2017, 53,
1405–1408.
[13] a) V. Martí-Centelles, A. L. Lawrence, P. J. Lusby, J. Am. Chem. Soc. 2018,
140, 2862–2868; b) Y. Domoto, M. Abe, T. Kikuchi, M. Fujita, Angew.
Chem. Int. Ed. 2020, 59, 3450–3454; Angew. Chem. 2020, 132, 3478–
3482; c) C. M. Egger, C. H. G. Jakob, F. Kaiser, O. Rindle, P. J. Altmann,
Crystallographic data: Deposition numbers 2043712, 2043713,
2043714, 2043715, 2043716, 2043717, 2043718, 2043719, and
2043720 contain the supplementary crystallographic data for this
paper. These data are provided free of charge by the joint Cam-
bridge Crystallographic Data Centre and Fachinformationszentrum
Karlsruhe Access Structures service.
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4668
ꢀ 2020 Wiley-VCH GmbH

Full Paper
doi.org/10.1002/chem.202004918
Chemistry—A European Journal
R. M. Reich, F. E. Kühn, Eur. J. Inorg. Chem. 2019, 5059–5065; d) T. A.
Young, V. Martí-Centelles, J. Wang, P. J. Lusby, F. Duarte, J. Am. Chem.
Soc. 2020, 142, 1300–1310.
ski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, T. Vreven, K. Throssell, J. A. Montgomery, Jr., J. E. Peralta, F.
Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov,
T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C.
Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam, M. Klene, C.
Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O. Farkas,
J. B. Foresman, D. J. Fox, Gaussian, Inc., Wallingford CT, 2016.
[31] G. R. Desiraju, P. S. Ho, L. Kloo, A. C. Legon, R. Marquardt, P. Metrangolo,
P. Politzer, G. Resnati, K. Rissanen, Pure Appl. Chem. 2013, 85, 1711–
1713.
[32] a) J. P. M. Lommerse, A. J. Stone, R. Taylor, F. H. Allen, J. Am. Chem. Soc.
1996, 118, 3108–3116; b) M. T. Messina, P. Metrangolo, W. Panzeri, E.
Ragg, G. Resnati, Tetrahedron Lett. 1998, 39, 9069–9072; c) P. Metrango-
lo, G. Resnati, T. Pilati, S. Biella, Halogen Bonding: Fundamentals and Ap-
plications, Vol. 126, Springer, Heidelberg, 2008, 105–136.
[33] A. Mukherjee, G. R. Desiraju, IUCrJ 2014, 1, 49–60.
[14] a) H. Abe, K. Ohtani, D. Suzuki, Y. Chida, Y. Shimada, S. Matsumoto, M.
Inouye, Org. Lett. 2014, 16, 828–831; b) D. Suzuki, H. Abe, T. Minami, S.
Matsumoto, M. Inouye, Chem. Lett. 2017, 46, 1740–1742; c) I. Popov, T.-
H. Chen, S. Belyakov, O. Daugulis, S. E. Wheeler, O. S. Miljanic, Chem. Eur.
J. 2015, 21, 2750–2754.
[15] C. M. Kane, O. Ugono, L. J. Barbour, K. T. Holman, Chem. Mater. 2015, 27,
7337–7354 and reference therein.
[16] B. Som, S. R. Salpage, J. Son, B. Gu, S. G. Karakalos, M. D. Smith, L. S. Shi-
mizu, CrystEngComm 2017, 19, 484–491.
[17] K. Roy, C. Wang, M. D. Smith, M. B. Dewal, A. C. Wibowo, J. C. Brown, S.
Ma, L. S. Shimizu, Chem. Commun. 2011, 47, 277–279.
[18] S. Dawn, M. B. Dewal, D. Sobransingh, M. C. Paderes, A. C. Wibowo,
M. D. Smith, J. A. Krause, P. J. Pellechia, L. S. Shimizu, J. Am. Chem. Soc.
2011, 133, 7025–7032.
[19] S. R. Salpage, Y. Xu, B. Som, A. J. Sindt, M. D. Smith, L. S. Shimizu, RSC
Adv. 2016, 6, 98350–98355.
[34] A. I. Kitaigorodskii, Organic Chemical Crystallography, Consultants
Bureau, New York, 1961, 65–112.
[20] O. B. Berryman, C. A. Johnson, L. N. Zakharov, M. M. Haley, D. W. John-
son, Angew. Chem. Int. Ed. 2008, 47, 117–120; Angew. Chem. 2008, 120,
123–126.
[21] C. N. Carroll, O. B. Berryman, C. A. Johnson, L. N. Zakharov, M. M. Haley,
D. W. Johnson, Chem. Commun. 2009, 2520–2522.
[22] J. M. Engle, P. S. Lakshminarayanan, C. N. Carroll, L. N. Zakharov, M. M.
Haley, D. W. Johnson, Cryst. Growth Des. 2011, 11, 5144–5152.
[23] J. M. Engle, C. N. Carroll, D. W. Johnson, M. M. Haley, Chem. Sci. 2012, 3,
1105.
[24] J. M. Engle, P. S. Singh, C. L. Vonnegut, L. N. Zakharov, D. W. Johnson,
M. M. Haley, CrystEngComm 2014, 16, 3703–3706.
[35] D. Braga, D. D’Addario, S. L. Giaffreda, L. Maini, M. Polito, F. Grepioni,
Top Curr. Chem. 2005, 254, 71–94.
[36] a) V. A. Blatov, A. P. Shevchenko, V. N. Serezhkin, J. Appl. Crystallogr.
2000, 33, 1193; b) V. A. Blatov, IUCr CompComm Newsletter 2006, 7, 4–
38; c) V. A. Blatov, A. P. Shevchenko, D. M. Proserpio, Cryst. Growth Des.
2014, 14, 3576–3586.
[37] V. A. Blatov, M. O’Keeffe, D. M. Proserpio, CrystEngComm 2010, 12, 44–
48.
[38] I. A. Baburin, V. A. Blatov, L. Carlucci, G. Ciani, D. M. Proserpio, J. Solid
State Chem. 2005, 178, 2452–2474.
[39] A. L. Spek, J. Appl. Crystallogr. 2003, 36, 7–13.
[25] C. L. Vonnegut, A. M. Shonkwiler, L. N. Zakharov, M. M. Haley, D. W.
Johnson, Chem. Commun. 2016, 52, 9506–9509.
[26] J. A. Lohrman, C.-L. Deng, T. A. Shear, L. N. Zakharov, M. M. Haley, D. W.
Johnson, Chem. Commun. 2019, 55, 1919–1922.
[27] a) A. M. S. Riel, D. A. Decato, J. Sun, C. J. Massena, M. J. Jessop, O. B. Ber-
ryman, Chem. Sci. 2018, 9, 5828–5836; b) A. M. S. Riel, R. K. Rowe, E. N.
Ho, A.-C. C. Carlsson, A. K. RappØ, O. B. Berryman, P. S. Ho, Acc. Chem.
Res. 2019, 52, 2870–2880.
[40] L. J. Barbour, Chem. Commun. 2006, 1163–1116.
[41] a) M. J. Turner, S. Grabowsky, D. Jayatilaka, M. A. Spackman, J. Phys.
Chem. Lett. 2014, 5, 4249–4255; b) J. Turner, S. P. Thomas, M. W. Shi, D.
Jayatilaka, M. A. Spackman, Chem. Commun. 2015, 51, 3735–3738;
c) C. F. Mackenzie, P. R. Spackman, D. Jayatilaka, M. A. Spackman, IUCrJ
2017, 4, 575–587; d) S. L. Tan, M. M. Jotanib, E. R. T. Tiekink, Acta Crystal-
logr. Sect. E 2019, 75, 308–318; e) S. L. Tan, E. R. T. Tiekink, Acta Crystal-
logr. Sect. E 2019, 75, 1–7.
[28] G. R. Desiraju, J. Am. Chem. Soc. 2013, 135, 9952–9967.
[29] a) K. Raatikainen, K. Rissanen, Chem. Sci. 2012, 3, 1235–1239; b) P. Me-
trangolo, F. Meyer, T. Pilati, G. Resnati, G. Terraneo, Angew. Chem. Int. Ed.
2008, 47, 6114–6127; Angew. Chem. 2008, 120, 6206–6220; c) W. X. Wu,
H. Wang, W. J. Jin, Cryst. Growth Des. 2018, 18, 6742–6747; d) P. Metran-
golo, G. Resnati, Chem. Eur. J. 2001, 7, 2511–2519.
[42] M. J. Turner, J. J. McKinnon, S. K. Wolff, D. J. Grimwood, P. R. Spackman,
D. Jayatilaka, M. A. Spackman, 2017. CrystalExplorer17. University of
Western Australia, http://hirshfeldsurface.net.
[43] F. Guagnini, PhD Thesis, 2018, Chapter 1, pp. 9–99. https://hdl.handle.-
net/1889/3765.
[30] Gaussian 09, Revision D.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Pe-
tersson, H. Nakatsuji, X. Li, M. Caricato, A. Marenich, J. Bloino, B. G. Jane-
sko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov,
J. L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J.
Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V. G. Zakrzew-
Manuscript received: November 11, 2020
Revised manuscript received: December 18, 2020
Accepted manuscript online: December 21, 2020
Version of record online: February 9, 2021
Chem. Eur. J. 2021, 27, 4660 –4669
www.chemeurj.org
4669
ꢀ 2020 Wiley-VCH GmbH