Reconciling Electrostatic and n→π* Orbital Contributions in Carbonyl Interactions

Article abstract of DOI:10.1002/anie.202005739

Interactions between carbonyl groups are prevalent in protein structures. Earlier investigations identified dominant electrostatic dipolar interactions, while others implicated lone pair n→π* orbital delocalisation. Here these observations are reconciled.

Full text of DOI:10.1002/anie.202005739

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Reconciling Electrostatic and n→π* Orbital Contributions in
Carbonyl Interactions
Authors: Kamila B. Muchowska, Dominic J Pascoe, Stefan Borsley,
Ivan V. Smolyar, Ioulia K Mati, Catherine Adam, Gary S
Nichol, Kenneth B Ling, and Scott Lee Cockroft
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Angewandte Chemie International Edition
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RESEARCH ARTICLE
Reconciling Electrostatic and n→* Orbital Contributions in
Carbonyl Interactions
[
a]
[a]
[a]
[a]
[a]
Kamila B. Muchowska, Dominic J. Pascoe, Stefan Borsley, Ivan V. Smolyar, Ioulia K. Mati,
[
a]
[a]
[b]
[a]
Catherine Adam, Gary S. Nichol, Kenneth B. Ling and Scott L. Cockroft*
[
a]
Kamila B. Muchowska, Dominic J. Pascoe, Stefan Borsley, Ivan V. Smolyar, Ioulia K. Mati, Catherine Adam, G. S. Nichol, and Scott L. Cockroft
EaStCHEM School of Chemistry
The University of Edinburgh
Joseph Black Building, David Brewster Road, Edinburgh EH9 3FJ, UK
E-mail: scott.cockroft@ed.ac.uk
[
b]
Kenneth B. Ling
Syngenta, Jealott’s Hill International Research Centre
Bracknell, Berkshire RG42 6EY, UK
Supporting information for this article is given via a link at the end of the document.
Abstract: Attractive interactions between carbonyl groups have
atom of another.[1a, 6] Conversely, it has also been suggested
that favourable C=O···C=O interactions may involve the
delocalisation of electron density (also known as induction,
polarisation, orbital interactions or stereoelectronic effects)[
from the lone pair (n) of a carbonyl donor into the antibonding
been studied extensively, primarily due to their prevalence in protein
structure. However, prior investigations have pointed to conflicting
origins; earlier investigations identified dominant electrostatic dipolar
interactions, while others have implicated lone pair n→* orbital
delocalisation. Here we reconcile these observations. A combined
experimental and computational approach confirmed the dominance
of electrostatic interactions in a new series of synthetic molecular
balances, while also highlighting the distance-dependent observation
of inductive polarisation manifested via n→* orbital delocalisation.
Computational fiSAPT energy decomposition and natural bonding
orbital analyses correlated with experimental data to reveal the
contexts in which short-range inductive polarisation augment
electrostatic dipolar interactions. Thus, we provide a framework for
reconciling the context-dependency of the dominance of electrostatic
interactions and the occurence of n→* orbital delocalisation in
C=O···C=O interactions.
7]
(*) orbital of an acceptor carbonyl, and denoted as an n→*
interaction.[
2d, 2e, 3a, 3f, 3g, 8]
Crystallographic and conformational
analyses have examined the distance and angle preferences of
close carbonyl contacts to posit that C=O···C=O interactions
may occur via n→* interactions without requiring dipolar
interactions.[ Furthermore, n→* orbital delocalisation in
carbonyl interactions has recently been further demonstrated to
stabilise the transition state of molecular rotors.[ Indeed, this
9]
7]
n→* delocalisation has been increasingly exploited for kinetic
reaction selectivity[
8a, 10]
and influencing dynamic covalent
equilibria.[11]
Despite the recent strong evidence for n→* delocalisation
from a range of experimental and theoretical studies, these
results remain unreconciled with earlier studies that indicated an
electrostatically driven interaction.[1a,
6]
Indeed, both the
Introduction
electrostatic and orbital delocalisation models qualitatively
account for the directionality of orthogonal C=O···C=O
Carbonyl groups are prevalent throughout chemistry and biology.
Interactions involving carbonyl groups are crucial in molecular
recognition processes,[1] and play a key role in determining the
conformation of small molecules,[2] proteins[3] and peptides.[4]
Despite the apparent importance of C=O···C=O interactions,
their physicochemical origin remains the subject of significant
debate. Attractive interactions between an oxygen atom of a
carbonyl group and the carbon atom of another were first
evidenced in the crystal structures of small, carbonyl-rich
molecules in the 1950s.[5] In all these cases, the length of the
C=O···C=O contact was less than the sum of the van der Waals
radii, and in some cases, C=O···C=O interactions would even
form in preference to C=O···HN hydrogen bonds.[5d] Indeed, the
structures of -helices and -sheets are determined not only by
C=O···HN hydrogen bonds, but also by competitive C=O···C=O
attractive forces, which account for the characteristic sheared
displacement of interacting peptide chains.[3b, 3c]
interactions resembling the Bürgi-Dunitz nucleophile–carbonyl
trajectory.[12] Moreover, both the competing dipolar and orbital
interaction models of C=O···C=O interactions are supported by
analyses of quantitative experimental data obtained using
different families of molecular torsion balances.[2d, 2e, 3f, 6, 10b, 13]
Here we set out to determine whether it is possible to
reconcile the competing electrostatic and orbital-based models
of C=O···C=O interactions. The nature of the interaction was
examined in different contexts in which interaction geometries
and solvents were varied. We synthesised a new series of
molecular torsion balances to quantify a range of C=O···C=O
interactions (Figure 1). Carbonyl interactions were screened in
1
2 different solvents to enable an empirical dissection of the
intramolecular carbonyl interaction from the modulating influence
of the solvent effects (Figure 2). Theoretical fiSAPT energy
partitioning was used to compare the electrostatic, exchange,
dispersion and induction (orbital) components in different
contexts (Figure 3). Finally, the geometry-dependent extent to
which orbital delocalisation augments electrostatic C=O···C=O
interactions was examined (Figures 4 and 5).
Carbonyl interactions were initially considered to be driven
by electrostatics. Orthogonal C=O···C=O dipolar interactions
can occur between the electron-rich oxygen atom of one
carbonyl group and the partial positive charge of the carbon
1
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Figure 1. Molecular balances examined in the present investigation of
C=O···C=O interactions. A) Newly designed balance series 1-X. B) Balance 2
previously reported by Diederich.[
reported by Raines.
6,
13]
C) Balance series 3-Y previously
[
2e]
Figure 2. A) Experimental conformational free energies (Gexp) measured in
19
1
1
2 different solvents by F{ H} NMR spectroscopy (376.5 MHz, 298 K).
Negative Gexp values are defined as a preference for the closed conformation.
Corresponding minimised structures (B3LYP/6-31G*) of each molecular
balance calculated in the gas phase are shown. Structures minimised using
B97X-D/6-31G* showed minimal change from B3LYP/6-31G* structures
Results and Discussion
Experimental Evaluation of Carbonyl Interactions
(Figure S46, Supporting Information). X-ray structures are given in
Molecular balances are useful tools for the quantitative study of
interactions and their associated solvent effects, since the
conformational equilibrium position is determined by differences
in the intramolecular interactions and relative solvation energies
of each conformer.[14] For example, the molecular balance
Section S2.4, Supporting Information. All data and errors are tabulated in
Table S16, Supporting Information. B) Dissected interaction components using
Hunter’s / hydrogen-bond model[21] (see Section S3.3, Supporting
Information).
structures shown in Figure
1
accommodate C=OC=O
interactions in the closed conformer (right) that are absent in the
open conformer (left). Diederich and Raines previously
employed molecular balances 2[6, 13] and 3-Y (Figure 1B and
the closed conformer of each balance was confirmed
computationally (B3LYP/6-31G* and B97X-D/6-31G*, Section
S4.1, Supporting Information), and via X-ray crystallography for
balances 1-H and 1-Me (see Section S2.4, Supporting
Information, CCDC deposition numbers: 1871050–1871051).
Solution-phase conformers were assigned by HMBC and
NOESY NMR spectroscopy (see Section S2.3, Supporting
Information), and conformational free energy differences were
measured by 19F{ H} NMR spectroscopy in 12 different solvents
(Figure 2, Section S3.1, Supporting Information).
[2e]
1
C) respectively to study C=OC=O interactions, but came to
different conclusions in regards to the major energetic
contributions.[2d, 2e, 3f, 6, 13] Diederich determined the carbonyl
interaction in balance 2 to be driven by electrostatics, while
Raines found n→* orbital delocalisation between carbonyl
groups to play an important role in the 3-Y series of balances.
To investigate the apparent incongruity regarding the nature of
carbonyl interactions we devised a new series of molecular
balances 1-X to supplement the existing datasets (Figure 1A).
Formamide balance series 1 is derived from molecular balances
previously used to study solvent effects,[14a, 15] H-bonding[16] and
chalcogen bonding interactions.[17] The minimal design of
balance series 1-X simplifies the interpretation of experimental
data and computational analysis of the experimentally
determined conformational preferences. Since rotation around
the formamide bond is slow on the NMR timescale, discrete
peaks corresponding to the open and closed conformers can be
observed. Thus, integration of the conformer peaks provides
direct access to the conformational equilibrium constant, K,
which can be used to determine the conformational free energy
difference, Gexp = −RT ln K.
1
Molecular balance 1-H generally favoured the open
conformer where no C=O···C=O contact could be formed (+1 to
−
1
+2 kJ mol ). However, molecular balances 1-Me, 1-OMe and
1-NMe
2
favoured the closed conformer, in which a C=O···C=O
−1
contact was formed, in most solvents (−4 to −1 kJ mol ). In
contrast, a series of structurally similar balances, but bearing
non-carbonyl ortho-substituents, generally favoured the open
conformer (see Section S2.1 and S3.1, Supporting Information).
Contrasting with prior examinations of substituent effects in
formamide
molecular
balances,[14a]
the
experimentally
determined Gexp values for balance series 1-X correlated poorly
with calculated electrostatic potentials over the X-substituted
aromatic ring (Figures S30 and S31, Supporting Information).
The above observations are consistent with intramolecular
interactions between the carbonyl groups playing a major role in
governing the equilibrium position of balance series 1-X. Further
supporting this assertion, non-covalent interaction (NCI) plots
confirmed attractive interactions between the carbonyl groups
The molecular balances in series 1-X were synthesised as
described in Section S2.2 of the Supporting Information (Figure
1
A). The occurrence of C=OC=O contacts (between the
formamide oxygen and each X-substituted carbon, Figure 2) in
(
Figure S63, Supporting Information).
2
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Evaluation of Electrostatic Solvent Effects
Solvents exert important influences on the conformational
preferences of molecular balances.[14b, 16, 19] However, the
conformational free energy differences of the 1-X series showed
only moderate solvent dependence, with similar conformational
free energy differences in polar and apolar solvents (Figure 2).
This level of solvent independence is surprising given that the
conformational free energies of closely related formamide
molecular balances were more strongly dependent on the H-
bond donor and acceptor ability of the solvent.[14a] Moreover,
energetic solvent independence may be indicative of the
presence of significant electron delocalisation in the interaction,
and could indicate the small significance of electrostatic forces in
C=O···C=O interactions.[17, 20]
The experimentally determined Gexp values correlated
moderately with some solvent parameters (Section S3.2,
Supporting Information), but the best insights were gained using
Hunter’s / hydrogen-bond model.[21] The same approach has
previously been shown to account for solvent competition in the
conformational equilibria of molecular balances,[14b, 19a, 22] and
involves iterative least-squares fitting of the experimentally
obtained Gexp values against those predicted by the model as
the H-bond donor and acceptor properties of the solvent are
varied (Section S3.2, Supporting Information). The resulting
dissected differences in the intramolecular interaction energy
Figure 3. Total and dissected interaction energies between the coloured
functional groups calculated using fiSAPT and SAPT for A) the 1-X series
24]
(
fiSAPT) and 2 (SAPT) and C) the 3-Y series (fiSAPT).[ SAPT calculations
[
6]
for 2 used the isolated fragment of the known X-ray structure shown. B)
Calculated differences in the total fiSAPT energies of the interactions between
the coloured structural fragments in the open and closed conformers
(
Eexp) and corresponding changes in the H-bond donor and
acceptor constants ( and ) between the open and closed
conformers are listed Figure 2B. The  and  values indicate
the extent to which competitive H-bonding interactions with the
solvent attenuate the intramolecular electrostatic interactions
between the carbonyl groups. Most significantly, the empirically
(SAPTtotal) correlate with both the empirically dissected intramolecular
interaction energy difference between the open and closed conformers of
series 1-X (Eexp from Figure 2B), and D) experimental conformational energy
[2e]
differences for series 3-Y measured in CDCl
performed using PSI4
3
(Gexp).
Calculations
[18]
at SAPT0/6-311G* on B3LYP/6-31G* minimised
dissected
solvent-independent
intermolecular
interaction
geometries. Alternative calculations and minimisations performed using
additional diffuse and polarisation functions provided similar results
2
energies Eexp correlated well (R = 0.92) with the change in the
interaction energies occurring between the carbonyl groups
(B97X-D/6-31G* and B3LYP/6-311+G**, jun-cc-pVDZ, aug-cc-pVQZ, see
Section S4.3, Supporting Information).
(
structural fragments highlighted in pink in Figure 3A) upon
flipping from the open to the closed conformation, as calculated
using fiSAPT (SAPTtotal in Figure 3B, see Section S4.3,
Supporting Information and discussion continued below).[24b]
electron delocalisation), dispersion, and exchange repulsion to
the carbonyl interactions of interest (Figures 3A and 3C).
[24]
Only small variations in the exchange, induction and dispersion
components across balance series 1-X and 3-Y were observed.
The largest variation was found in the electrostatic term, which
accordingly makes a dominant contribution to the total SAPT
energy of the carbonyl interactions in both series.
Dissecting the Origin of C=O···C=O Interactions
Symmetry adapted perturbation theory (SAPT) is a powerful
computational tool for examining molecular interactions.[24]
Encouraged by the aforementioned correlation between
experiment and theory for series 1-X (Figure 3B), we expanded
our use of functional group intramolecular SAPT (fiSAPT)[24b] to
examine the 3-Y series (Figure 3C-D, Section S4.3, Supporting
Information). Once again, an excellent correlation (R2 = 0.99)
was found between the experimental conformational energies
Interestingly, both the experimental and calculated
substituent effect trends are reversed in series 1-X compared to
3
-Y. The trend makes most intuitive sense in series 3-Y where
the C=O···C(=O)Y carbonyl-carbonyl interactions are most
stabilised by electron-withdrawing Y substituents. The different
trends can be rationalised by secondary interactions occurring
alongside the C=O···C=O interactions in series 1-X. Firstly, the
electrostatic interaction between the carbonyl groups is less
favourable in 1-H, which has a conformational minimum in which
the dipoles of the carbonyl groups repel one another (top right,
Figures 2A and S49 and Section S4.3, Supporting Information).
In contrast, the carbonyl groups attached to the phenyl ring in
the other 1-X balances are flipped relative to 1-H and instead
form favourable dipolar interactions. Secondly, the carbonyl-
(
Gexp)[2a] and the change in the total fiSAPT interaction energy
between the carbonyl groups (highlighted in purple in Figure 3C)
upon flipping from the open to the closed conformation
(
SAPTtotal, Figure 3D). The SAPTtotal energies calculated in
the gas phase were much more favourable than the
corresponding experimentally determined conformational
energies (Eexp and Gexp). This difference likely provides an
indication of the magnitude of the attenuating influence of the
solvent, both in terms of competitive dispersion[23] and
electrostatic interactions.[12][15]
carbonyl contacts in compounds 1-Me and 1-NMe
be more stabilised than in 1-OMe. Non-covalent interaction
NCI) plots (Figure S63, Supporting Information)[27] indicated that
additional secondary interactions between the formyl oxygen
2
appeared to
Moreover, the SAPT approach facilitated the energetic
dissection of electrostatics, induction (which includes n→*
(
3
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and the methyl groups in both 1-Me and 1-NMe
additional electrostatic (and to a lesser extent, inductive and
dispersion) stabilisation observed in the fiSAPT dissection
2
account for the
any of the calculated or X-ray structures of balances 1-H or
1-Me (Sections S2.4 and S4.1, Supporting Information).
Overall, evidence from SAPT calculations (Figure 3), orbital
energy stabilisation (Figures 4A and B), NBOs (Section S4.4,
Supporting Information), and carbonyl pyramidalisation[2e] all
point to the occurrence n→* electron delocalisation in series
3-Y, but not for series 1-X or 2. These differences suggest that
such orbital delocalisation is geometry dependent. Indeed, the
C=OC=O interactions in balance series 1-X have a 1,6-
relationship, while those in balance series 3-Y (and peptides)
have a 1,5-relationship (and have orbital interactions). Similarly,
C=Ochalcogen bonds with a 1,5-relationship are known to
have important energetic orbital contributions (n→*), while
(
Figures 3A and 3C). Hence, the secondary C=O···H
interactions in 1-Me and 1-NMe , combined with the flipped
orientation of the carbonyl group in 1-H, account for the
apparently inverted electronic trend observed both
experimentally and theoretically in series 1-X compared to series
-Y.
3
C
2
3
While the fiSAPT analysis and correlations against
experimental data presented in Figure 3 appear reasonable, we
caution that such energetic dissections are non-physical,
especially when performed intramolecularly across covalent
bonds in the fiSAPT variant.[24] Contrasting with the tightly
constrained intramolecular geometries of balance series 1-X and
[17, 25]
those with 1,6-relationships may not.
3
-Y, the larger folding structure of balance 2 facilitated
intermolecular SAPT analysis on a fragment of the known X-ray
structure[6] of 2 (Figure 3A, blue). Reassuringly, the energetic
composition of the carbonyl interactions in balance 2 calculated
using SAPT was remarkably similar to those calculated for the
1
-X and 3-Y series using fiSAPT (Figure 3A and 3C, blue vs.
pink and purple). Consistent with the SAPT analysis above,
Diederich concluded that the carbonyl interactions in balance 2
were best described as orthogonal dipolar interactions.[6, 13]
Given Raines’ extensive evidence supporting the importance of
n→* delocalisation in carbonyl interactions, we were surprised
to find that the induction contribution to the conformational
preferences of balance series 3-Y was only slightly greater than
that seen for series 1-X.
Reconciling the Observation of n→* Orbital Contributions
Having found surprisingly similar behaviour in the carbonyl
interactions of all three series of balances, we next sought to
reconcile the observation of n→* orbital contributions. The
simple designs of series 1-X and 3-Y makes it relatively easy to
calculate and identify any molecular orbitals that are stabilised
on changing from the open to the closed conformer. Thus,
orbital energies were calculated for the open and closed
conformers and plotted against each other for the balance series
1
-X and 3-Y (Figures 4A and 4B, Section S4.5, Supporting
Information). No points deviate from the correlation in Figure 4A,
indicating no specific stabilisation of any orbitals in the closed
conformers of the 1-X series. In contrast, two classes of
molecular orbitals were found to be stabilised in the closed
conformers of the 3-Y series (orange and teal points Figure 4B).
Visualisation of these molecular orbitals revealed that they
corresponded to delocalisation of both oxygen lone pairs on the
formyl carbonyl into the adjacent carbonyl in the closed
conformer (i.e. n→* interactions, Figure 4B, right). The
occurrence of n→* delocalisation was confirmed using natural
bonding orbital (NBO) calculations (Section S4.4, Supporting
Figure 4. Correlation of calculated orbitals energies in the open vs closed
conformers of A) balance series 1-X and B) Balance series 3-Y. The second
frag
aromatic ring in balance series 1-X was replaced with a proton to give
1-X
to avoid orbital splitting arising from the canonical resonance forms of the
aromatic electrons (See section S4.5, Supporting Information). Data points
that fall below the trend formed by grey points are stabilised in the closed
conformer due to the n→* electron delocalisation from both lone pairs of the
frag
carbonyl donor. For balance series
1-X, no special stabilisation of orbitals
between open and closed conformation was observed, while for balance
series 3-Y two sets of molecular orbitals (orange and teal) were observed
corresponding to stabilisation of the carbonyl oxygen lone pairs into the
adjacent carbonyl group via n→* interactions.
Information).[17]
Second-order
perturbation
energies
corresponding to these NBOs were calculated to contribute up to
−1
9
.4 kJ mol . In contrast, corresponding stabilising NBOs were
not found in balance 2 or the 1-X series (except for 1-Me in
certain contexts, Section S4.4, Supporting Information, vide
infra). Similarly, pyramidalisation of the acceptor carbon atom
Geometric Influences on n→* Orbital Contributions
We next set out to examine the geometric dependency on the
nature of C=O···C=O interactions. Molecular balances from the
(
akin to the formation of a partial covalent bond) provides
irrefutable evidence of n→* delocalisation in the 3-Y series of
3
-Y series contained much closer C=O···C=O contacts than
balances.[ However, no such pyramidalisation was observed in
2e]
those in 2, while those of series 1-X lay between the two
4
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RESEARCH ARTICLE
extremes (Table S20, Supporting Information). Thus, we
reasoned that closer carbonyl-contacts could facilitate better
orbital overlap, and therefore the occurrence of orbital
delocalisation. Indeed, Shimizu and co-workers recently found
that the intramolecular stabilisation of transition states via n→*
interactions is strongly distance dependent.[7]
Sahariah and Sarma previously performed a computational
examination on the geometry dependence of carbonyl
interactions,[26] however, this prior work focused on angular
dependence rather than separation distance. Hence, for our
calculations, the relative geometry of the C=OC=O interactions
in the balances 1-Me, 2 and 3-H were arbitrarily locked in place
NBO calculations were performed at each separation and the
resulting sum of the 2nd order perturbation energies
corresponding to n→* delocalisation of both carbonyl lone
pairs was plotted (Figure 5, Section S4.4, Supporting
nd
Information). The 2 order perturbation energies of these n→*
NBOs become increasingly favourable as the OC distance
decreases for all three balance models. The distance
dependencies of the energies for the 1-X and 2 models were
very similar, but notably several kJ mol−1 less stable than the 3-Y
model at shorter separations. The dotted lines in Figure 5
correspond to the maximum and minimum OC distances
observed in each balance series 1-X, 2 and 3-Y (Table S20,
Supporting Information). Balance 2 had the longest OC
distance, and correspondingly, the weakest orbital contribution.
Conversely, balance series 3-Y showed the shortest range of
OC contacts, and featured the strongest n→* contribution.
Meanwhile, the 1-X series hosted OC interactions with
intermediate distances lying between those found in balance 2
and the 3-Y series. Indeed, on examining the full balance
structures of the 1-X series, weak stabilising n→* NBOs were
only observed in the X-ray and B97X-D/6-31G* minimised
structures of 1-Me, which were by far the shortest OC contacts
found in the 1-X series (Table S20 and Figure S57, Supporting
Information). In addition, the energies of the n→* delocalisation
energies across all three balance series were also surprisingly
insensitive to the angle of deflection between the plane of the
acceptor carbonyl (e.g. Bürgi-Dunitz angle = 107°),[ which was
further confirmed via a systematic scan of interaction angles and
additional SAPT analysis (Figures S59, S60 and S56,
Supporting Information).[26] This minimal angle dependency
coupled with the strong distance-dependency observed across
three different balance models suggests that OC separation is
key to determining whether orbital delocalisation occurs
alongside the ever-present electrostatic stabilisation in carbonyl-
carbonyl interactions.
(
based on minimised B3LYP/6-31G* geometries), and the OC
distance systematically varied.
12]
Conclusion
In summary, we have performed a combined experimental and
theoretical investigation of carbonyl interactions in a range of
contexts and solvents. Previous investigations into the nature of
carbonyl interactions identified conflicting physiochemical origins
for the interaction, implicating the dominance of either
electrostatics[
6, 13]
or orbital delocalisation.
[3f],[2d],[2e, 7]
We
supplemented the existing data sets based on balance 2 and
series 3-X by synthesising new molecular balance series 1-X.
Experimentally determined conformational free energies
confirmed the presence of carbonyl contacts in balance series
1
-X. The significance of electrostatics in determining the
conformational preference was confirmed by applying Hunter’s
/ hydrogen-bond model[21] across 12 solvents. Computational

SAPT and fiSAPT analysis indicated that the carbonyl
interactions in all three balance series were largely governed by
electrostatics in the gas phase (Figure 3). A pairwise analysis of
orbital energies indicated that carbonyl lone pairs were stabilised
by n→* delocalisation in series 3-Y, but not series 1-X or
balance 2 in the geometries examined (Figure 4). The disparate
occurrence of orbital interactions was reconciled by examining
the influence of OC separation distance using NBO
calculations. NBOs indicated the occurrence of n→*
Figure 5. Total 2nd order perturbation energies corresponding to n→*
electron delocalisation determined for both lone pairs in simplified models of
the C=O···C=O interactions hosted within balance series A) 1-X, B) 2, and C)
3-Y. Energies were calculated using NBO6.0, see Section S4.4, Supporting
Information for details. Deflection angles from the plane of the acceptor
carbonyl are indicated (e.g. Bürgi-Dunitz angle = 107°).[12] Shaded areas
correspond to O···C distances observed in the respective balance series
(Table S20, Supporting Information).
5
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delocalisation for the short contacts within series 3-Y, but not for
the longer-range interactions occurring in balance 2. The
carbonyl-carbonyl distances in balance series 1-X were
intermediate between those found in series 3-Y and balance 2,
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We thank Syngenta (DJP, KL), the EPSRC (KM EP/H021620/1),
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Entry for the Table of Contents
Carbonyls reconciled: Electrostatics and orbital interactions have both been implicated in governing carbonyl interactions. A
combined experimental and computational approach reconciles these conflicting explanations of the physiochemical origin of the
interaction, demonstrating that orbital delocalisation augments electrostatic control, but for very close carbonyl contacts.
8
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