# Bond-dissociation energies to probe pyridines electronic effects on organogold(III) complexes: from methodological developments to application in $\pi$-backdonation investigation and catalysis

Lyna Bourehil, Clément Soep, Sopheak Seng, Sarah Dutrannoy, Stacy

Igoudjil, Jérémy Forté, Geoffrey Gontard, Denis Lesage, Benoît Bertrand,

Héloïse Dossmann

► To cite this version:

Lyna Bourehil, Clément Soep, Sopheak Seng, Sarah Dutrannoy, Stacy Igoudjil, et al. Bond-dissociation energies to probe pyridines electronic effects on organogold(III) complexes: from methodological developments to application in $\pi$-backdonation investigation and catalysis. Inorganic Chemistry, 2023, 62 (33), pp.13304-13314. 10.1021/acs.inorgchem.3c01584. http://dx.doi.org/10.1021/acs.inorgchem.3c01584

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Submitted on 6 Sep 2023

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Bond dissociation energies to probe pyridines electronic effects on organogold(III) complexes: from methodological developments to application in π-backdonation investigation and catalysis

Lyna Bourehil,<sup>a,b</sup> Clément Soep,<sup>a</sup> Sopheak Seng,<sup>a,c</sup> Sarah Dutrannoy,<sup>a</sup> Stacy Igoudjil,<sup>a</sup> Jérémy Forté,<sup>a</sup> Geoffrey Gontard,<sup>a</sup> Denis Lesage,<sup>a*</sup> Benoît Bertrand<sup>a*</sup> and Héloïse Dossmann<sup>a*</sup>

<sup>a</sup> Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, F-75005 Paris, France

<sup>b</sup> Synchrotron SOLEIL, L'Orme des Merisiers, St Aubin, BP 48, F-91192 Gif-sur-Yvette, France

<sup>c</sup> Institute of Physical Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 2, D-76131 Karlsruhe, Germany

**ABSTRACT:** In this work, we report on the synthesis of several organogold(III) complexes based on 4,4'-diterbutylbiphenyl (C^C) and 2,6-bis(4-terbutylphenyl)pyridine (C^N^C) ligands and bond with variously substituted pyridine ligands (pyrR). Altogether 33 complexes have been prepared and studied with mass spectrometry using higher-energy collision dissociation (HCD) in an Orbitrap mass spectrometer. A complete methodology including the kinetic modeling of the dissociation process based on the Rice-Ramsperger-Kassel-Marcus (RRKM) statistical method is proposed to obtain critical energies E₀ of the pyrR loss for all complexes. The capacity of these E₀ values to describe the pyridine ligand effect is further explored, at the same time as more classical descriptors such as ¹H pyridinic NMR shift variation upon coordination and X-ray diffraction measured Au-N^pyrR bond length. An extensive theoretical work, including density-functional theory (DFT) and domain-based local pair natural orbital coupled-cluster theory (DLPNO-CCSD(T)) methods, also is carried out to provide bond-dissociation energies which are compared to experimental results. Results show that dissociation energy outperforms others descriptors, in particular to describe ligands effects over a large electronic effects range as seen by confronting the results to the pyrR pKₐs values. Further insights into the Au-N^pyrR bond are obtained through an Energy-Decomposition Analysis (EDA) study which confirms the isolobal character of Au⁺ with H⁺. Finally, the correlation between the lability of the pyridine ligands towards the catalytic efficiency of the complexes could be demonstrated in an intramolecular hydroarylation reaction of alkyne. The results were rationalized considering both pre-catalyst activation and catalyst reactivity. This study establishes the possibility of correlating dissociation energy, which is a gas-phase descriptor, with condensed-phase parameters such as catalysis efficiency. It holds therefore great potential for inorganic and organometallic chemistry by opening a convenient and easy way to evaluate the electronic influence of a ligand towards a metallic center.

Through their steric and electronic effects, ligands play a crucial role in inorganic chemistry, with direct implications in organometallic catalysis, biomedicine or material science.<sup>1,2</sup> They influence the net electron density on the metallic center and constrain the access to the first coordination sphere. They are therefore able to drive its behavior and reactivity, leading for instance to high selectivity in chemical transformations. To access fine tuning of catalytic reaction pathways or material design a detailed knowledge of metal ligand interactions may thus be required in order to evaluate the steric and electronic influence of the latter. The classical model depicting electronic interactions between a metal and a ligand is the Dewar-Chatt-Duncanson model<sup>3</sup> which involves σ / π -donor and -acceptor capabilities of the ligand resulting in a global metal-ligand interaction. Over the years, many experimental methods and descriptors have been developed to evaluate the electronic effects resulting from the coordination of a ligand to a metal. One of the most well-known approach is the Tolman electronic parameter (TEP) applied to organometallic complexes possessing CO probe ligands and based on the determination of their infrared A₁-symmetrical CO-stretching frequency.<sup>4</sup> TEP has enabled the classification of phosphine ligands according to their donating capacity and was also extended to the classification of N-heterocyclic carbenes (NHCs) using [Ir/Rh(CO)₂Cl(L)] complexes.<sup>5</sup>

Another descriptor, the Huynh Electronic Parameter (HEP), implies ¹³C NMR spectroscopy and relies on the determination of the chemical shift of the carbenic carbon of a NHC ligand in *trans*-[[(NHC)PdCl₂(L)] and [(NHC)AuL]⁺ complexes.⁶ The donation strengths of various types of ligands were determined in this way, including NHCs, phosphines and N-donor ligands. Furthermore, Rocchigiani and Bochmann used the ¹H NMR chemical shift of hydride ligands in organogold(III) complexes to study the *trans*- and *cis*-influence of various ligands, including (C^N), (C^C), (C^N^C) and (C^C^N) chelates.⁷ Eventually, gas-phase studies have also been involved in this field with, for instance, the use of ionization energies⁸⁻¹⁰ or bond-dissociation energies (BDEs)¹¹,¹² as descriptors of the ligand electronic effects. Recently, our group was thus implicated in a project aiming at the evaluation of the ligand strengths in a series of [L-Au-CO]⁺ complexes (L being a phosphine, phosphite or NHC ligand) using Au-CO BDEs determined by two mass spectrometry (MS) - based methodologies, Blackbody Infrared Radiative Dissociation (BIRD)¹³ and collision-induced dissociation (CID) in the multi-collisional regime.¹⁴ With a similar approach to Tolman's, we determined that the variation of the Au-CO bonding energy could be linked to the ligands' electronic properties and that BDE could accordingly serve as a valuable descriptor for these effects.
Although usually performing well, all the above-cited experi-
mental approaches rely on the use of a probe ligand such as
C≡O for Tolman/BDE and a N-heterocyclic carbene (NHC) for
Huynh parameter. The need for such specific ligands dramati-
cally limits the range and diversity of the systems to be studied
but may also lead to a lack of sensitivity, making such approach
difficult to generalize. We thus endeavored to develop a new
methodology free of such constraint. In the present project, we
propose the investigation of the electronic influence of vari-
ously substituted pyridines bound to several Au(III) scaffolds
using bond-dissociation energy measurements of the Au-N<sup>pyrR</sup>
bond. The systems were designed without probe ligands and the
unique imposed constraint was the lability of the pyridines in
order to access the bonding energy. The designed gold (III)
complexes are 33 and of the [(C^C)Au(NHC/PPh₃)L]⁺ and
[(C^N^C)AuL]⁺ type with L being the pyridine ligand of inter-
est (Scheme 1). These (C^C) and (C^N^C) chelating ligands are
known for their high stability¹⁵, ¹⁶ and a large panel of applica-
tions in fundamental organometallic chemistry,¹⁷, ¹⁸ photolumi-
nescence¹⁹⁻²¹ and biology.¹⁵, ²² Three scaffolds were chosen in
order to access a large range of electronic effect. Aryl ligands
(complexes 1 and 2) are indeed known to have a higher *trans*
influence compared to N-donor ligands (complexes 3).²³

<figure><img src="image_1.png" /><figcaption>**Scheme 1.** Structures of the 33 studied organogold(III) complexes. The reaction yield is indicated in brackets for each R substituent. The numbers on the pyridine indicate the R position.</figcaption></figure>

The effect of pyridine substitution on the metal enrichment was
evaluated by determining the dissociation energy [[Au]-N<sup>pyrR</sup>]<sup>+</sup>
→ [Au]<sup>+</sup> + N<sup>pyrR</sup> ([Au] being one of the three scaffolds) using
higher-energy collision dissociation (HCD) available on an Or-
bitrap mass spectrometer. A statistical Rice-Ramsperger-Kas-
sel-Marcus (RRKM)<sup>24-27</sup> modeling was performed to determine
the critical energy (E<sub>0</sub>) of the fragmentation and compared with
several theoretical approaches, including density-functional
theory (DFT) and *ab initio* methods as well as energy decom-
position analysis (EDA). This newly-developed bond-energy
descriptor was compared to classical ones, i.e. X-ray diffraction
bond lengths and ¹H(pyrR) NMR shifts variation upon coordi-
nation and all rationalized by means of the pK<sub>a</sub> values of the
free pyridines. Interestingly, the bond-dissociation energies ap-
pear much more efficient and reliable to describe the electronic
influence of the pyridines over the very large electronic effects
probed range. In the light of these results, the isolobality of the
Au(III) fragments with H<sup>+</sup> is discussed as well as the π-acceptor
contribution on the Au-pyrR interaction. Finally, a first step to
link this gas-phase descriptor to the condensed-phase reactivity
of the complexes is done by probing their catalytic activity in

an intramolecular hydroarylation reaction of alkyne and ration-
alizing it in the view of the Au-N^pyrR^ bond strength.

RESULTS AND DISCUSSION

**Synthesis of the complexes.**

[[(C^C)Au(NHC)(pyrR)]PF₆] complexes **1a-nPF₆** were synthesized in two steps. First, the 1,3-dimethylbenzimidazol-3-ylidene (NHC) ligand was introduced onto the [(C^C)AuCl] moiety by using the silver-based transmetallation method with the [(C^C)AuCl]₂ dimer to form the [(C^C)Au(NHC)Cl] complex 1.²⁸ In a second step, the chlorido ligand was abstracted using silver hexafluorophosphate and replaced by variously substituted pyridines in para, meta and ortho position with excellent yields (Scheme 1). [[(C^C)Au(PPh₃)(pyrR)]PF₆ complexes **2a, e, f, h** and **iPF₆** were synthesized *via* a one-pot two-steps procedure starting by the introduction of the substituted pyridine onto the [(C^C)AuCl] scaffold followed by the abstraction of the chlorido ligand using silver hexafluorophosphate and the introduction of the triphenylphosphine ligand with satisfying to very good yields (Scheme 1). The [[(C^N^C)Au(pyrR)]PF₆ **3a-nPF₆** were synthesized from the [[C^N^C)AuCl] precursor by a modified reported procedure involving the abstraction of the chlorido ligand and using silver hexafluorophosphate and introduction of the substituted pyridines with good to excellent yield.

<figure><img src="image_2.png" /><figcaption>**Figure 1.** Crystal structures obtained for each of the three scaffolds: **1gPF<sub>6</sub>**, **2iPF<sub>6</sub>** and **3cPF<sub>6</sub>**. Ellipsoids are set at 50% probability and hydrogen atoms omitted for clarity (and dichloromethane for **3cPF<sub>6</sub>**). Only one complex of the asymmetric unit is shown for **1gPF<sub>6</sub>** and **2iPF<sub>6</sub>**. All XRD structural parameters are detailed in the SI (Figs. S1-S17).</figcaption></figure>

**X-ray diffraction analysis.** As a first probe of the donating capability of the pyridines towards the metal, a close inspection of the structural parameters may serve as a good indicator. Crystal structures of a large number of the studied complexes were obtained and are shown in Figs 1 and S1-17 and the Au-N<sup>pyrR</sup> bond lengths are given in Table S1 and Fig. 2. The structures of **1**, **2** and **3** series present the typical square-planar 4-coordinated geometry of Au(III) complexes with small distortions according to the chelating ligands used in agreement with reported data for (C<sup>^C</sup>)- and (C<sup>^N^C</sup>)-based Au(III) complexes.<sup>28-30</sup> Replacement of the chlorido ligand by the substituted pyridines in the [(C<sup>^C</sup>)Au(NHC)]<sup>+</sup> series does not modify the bond length and angles for the (C<sup>^C</sup>) and NHC ligands. In all [(C<sup>^C</sup>)Au(PPh<sub>3</sub>)(pyrR)]PF<sub>6</sub> **2PF<sub>6</sub>** structures, the pyridine ligand appears almost parallel to a phenyl ring of the PPh<sub>3</sub> placing the pyridine protons in the anisotropy cone of the phenyl ring explaining the shielding of this proton upon coordination observed by ¹H NMR spectroscopy (see below). To evaluate the metal-ligand bond strength, the Au-N<sup>pyrR</sup> bond lengths were considered (Table S1, Fig. 2). The first observation concerns the (C<sup>^N^C</sup>)-based complexes **3PF<sub>6</sub>** which present a significantly shorter Au-N<sup>pyrR</sup> bond length compared to (C<sup>^C</sup>)-based
1PF<sub>6</sub> and 2PF<sub>6</sub> complexes (around 2.05 Å vs. 2.13 Å, respectively).

This observation is in agreement with the known *trans* influ-
ence applied by N-donor ligands compared to aryl ones.<sup>23</sup> *Trans* influence of ligands indeed defines the electron-donating capa-
bility of a ligand towards the metal which results in the weak-
ening of the bond between the metal and the ligand in *trans*. Moreover, with the exception of **3IPF**<sub>6</sub> showing a slightly longer Au-N<sup>pyrR</sup> bond length (2.07 Å) compared to other [(C^N^C)Au(pyrR)]<sup>+</sup> complexes, no significant effect of the pyridine could be observed on the Au-N<sup>pyrR</sup> bond length in any of the three complexes series we studied. Altogether, these data suggest that Au-N<sup>pyrR</sup> bond length measurements are suitable to evaluate *trans* influence of the different scaffolds with the N-donor having a lower *trans* influence than the aryl ligand as reported in the literature<sup>23</sup> whereas it seems not suitable for discriminating *cis* influence and substituent effects.

<figure><img src="image_3.png" /><figcaption>**Figure 2.** Relation between the Au-N<sup>pyrR</sup> bond length measured by X-ray diffraction and the pK<sub>a</sub> of the corresponding free pyridines.</figcaption></figure>

¹H NMR analysis. Another classical descriptor of the elec-
tronic influence of ligand is the ¹H NMR shift difference which
can be observed upon coordination of the ligand and which can
be linked to the ligand donation capability towards the metal.
Previous works on Pt(II) and Pd(II) complexes bound to substi-
tuted pyridines have also reported on the linear correlation ob-
served between the pKₐ values of the free pyridines and the shift
of the ¹H NMR chemical shift (Δδ) of the pyridinic protons
upon coordination with the metals.³¹, ³² This comparison be-
tween the chosen descriptor (¹H Δδ) and the pKₐ appeared very
interesting to us as pKₐs are directly reflecting the donating ca-
pability of the pyridine and are easily manipulated by chemists.
A similar analysis was accordingly undertaken on our Au(III)
complexes. First, as seen in Fig. 3A, the ¹H shifts measured for
pyridinic H2/H6 and H3/H5 protons show a nearly linear de-
pendence with ¹H shifts of free pyridines. This indicates that the
decrease in the electron density of the pyridinic protons is fol-
lowing the same trend upon coordination. Furthermore, the
change in chemical shifts upon coordination was calculated and
it appeared more pronounced on the *meta* protons (H3/H5) than
on the *ortho* (H2/H6) ones, as already observed in the literature
for Au(III) complexes (Fig. 3B and C).³³ This behavior is spe-
cific to Au(III), as Pt(II) and Pd(II) complexes exhibit, on the
contrary, the highest deshielding on the H2/H6 pyridinic pro-
tons upon coordination.

Complexes 1PF<sub>6</sub> and 3PF<sub>6</sub> show the largest shifts on the H3/H5 protons, between 0.35 and 0.80 ppm for the *meta* ¹H position vs. 0.1-0.5 ppm for the *ortho* one. On the other hand, complexes 2PF<sub>6</sub> lead to a relatively small deshielding of the pyridines protons (below 0.3 ppm). This feature is attributed to the interaction taking place between the pyridine and the aromatic ring of the PPh<sub>3</sub> ligand as observed on the X-ray structures.

Confronting these Δ(δ) values with the pK<sub>a</sub> of the free pyridines indicates that only the 2PF<sub>6</sub> H2/H6 ¹H Δ(δ) exhibit an almost linear dependence to the pK<sub>as</sub> (R<sup>2</sup> = 0.991, Fig. 3B)). In this series, on the contrary to the others, only *para* substituted pyridines have been considered, as for the work of Kurpik *et al*.<sup>31</sup> and Lewis *et al.*,<sup>32</sup> which may explain this result. Changing the substituent from the *para* to the *meta* or *ortho* position on the pyridine possibly increases the steric interaction between the pyridine and the scaffold and thus affects the chemical shift of the pyridine protons. Accordingly, as pyridines *j-n* with substituents in position 2 and 3 have been considered for the scaffolds 1 and 3, the correlation between ¹H NMR Δ(δ) and pK<sub>as</sub> appears to be very poor (R<sup>2</sup> < 0.6). Note however that the H2/H6 and H3/H5 ¹H Δ(δ) of complexes 1 and 3 with only *para* substituted pyridines still do not relate well to the pK<sub>as</sub> (R<sup>2</sup> < 0.8, not shown), indicating that besides the position of the pyridine substituent, other factors influence the chemical shift of the protons of the pyridine ring and thus hinder the direct measurement of the electronic effect induced by the pyridine on Au(III) complexes. Thus, on the contrary on Pt(II) and Pd(II) complexes, ¹H NMR shifts may not serve as a reliable descriptor to evaluate the ligand donating effect on Au(III) complexes.

<figure><img src="image_4.png" /><figcaption>**Figure 3.** A) Relation between the ¹H NMR shifts of the H2/H6, H3/H5 protons of coordinated and free pyridines (almost-linear dependence (R²> 0.90)). Shift of the ¹H NMR shift between the pyridinic proton in position B) 2/6 or C) 3/5 of the coordinated pyridines vs. the pKₐ of the free pyridines. For R substituents in *ortho* or *meta* position (pyridines *k-n*), the most deshielded proton was considered.</figcaption></figure>

**Bond dissociation energy measurements.** Besides bond
lengths or ¹H NMR shifts, other experimental descriptors may
serve to evaluate the donating capability of a ligand. This can
for instance be the case of the bond strength value between the
metal and the ligand. Previous works in our group have already
shown the capability of bond dissociation energies (BDEs) to
efficiently evaluate *trans* ligand effect on Au(I) complexes.¹³,¹⁴
Following these results, it appeared interesting to probe BDE as
a descriptor of the Au(III)-pyridine interaction. To this end, the
Au-pyridine bond strength of the 3 series of complexes were
experimentally determined using a mass spectrometry (MS) -
based approach. MS is a very valuable tool for the determina-
tion of thermochemical quantities. As the complexes under
study already bear a positive charge, the experimental method
to determine the Au(III) - pyridines critical energies were
relatively easy to setup. By using collisional activation, performed in the HCD cell of an Orbitrap and under the multi-collisional regime in our case, it is thus possible to obtain survival yields over a large collision energy range. This yield represents the ratio of the intensity of the precursor ion over the sum the intensity of the precursor and the fragments. As simple way to compare bond strengths within the series of complexes would first consist in determining the energy required to fragment 50% of the precursor signal or to determine the extrapolation of the fragmentation onset from the fragment ion curve (see for instance ref. ³⁴). These procedures are often used for qualitative studies and have the advantage to be obtained directly from the energy-resolved mass spectra. The derived energies are however only relative and to obtain critical energies in an absolute scale, a thorough kinetic modeling of the process is required. Note that the thermochemical quantity obtained is a critical energy E₀ which refers to the energy difference between the transition state of dissociation and the precursor ion at 0 K. Electronic structure calculations usually provide bond dissociation energies (BDEs) which correspond to the enthalpy change of the dissociation reaction at 0 K. For processes occurring without reverse activation energy, E₀ and BDE are very close and can be directly compared. This will be the case in the present study for a direct cleavage mechanism.

<figure><img src="image_5.png" /><figcaption>**Figure 4.** **A)** Experimental (markers) and modeled (lines) survival yield curves (SY) obtained for the set of 33 complexes. The relation between measured critical energies (±1σ) and calculated bond-dissociation energies (with the *M06* method, see SI) is displayed for each family of complexes in **B)**, **C)** and **D)**.</figcaption></figure>

In a previous work, Bayat *et al.*³⁵ proposed a kinetic model, based on RRKM theory²⁴⁻²⁷ and using *MassKinetics* software,³⁶ to extract critical energy (E₀) from HCD fragmentation curves. In this approach, a calibration of the internal energy distribution deposited during the HCD experiment is performed and a linear relationship between the average internal energy of the ions <Eᵢₘ> and the collision energy in the laboratory frame (Eᵣₐb) is established for a model complex used as a reference (see SI for more details) and for which an initial guess of its critical energy has to be made. Following this approach, Bayat *et al.* were able to obtain a set of critical energies for ten hemicryptophane-guest complexes in excellent agreement with previously published data. In the present work, we first applied this approach but it was however not as satisfying because of the large differences in size or bond strength of our complexes which would have required an adjustment of the <Eᵢₘ> = f(Eᵣₐb) relationship

for each complex. Starting from there, we developed a new kinetic model shortly described here (and in details in the SI). For each complex, the average internal energy <Eᵢₘ> and its corresponding characteristic temperature Tᵣₐb are obtained by assuming a collision process in which all of the kinetic energy of the precursor ion is converted into internal energy after a certain number of collisions. This number varies for each complex and depends on Eᵣₐb, on the effective collision cross section of each complex which are determined by ion mobility experiments and on the inelasticity coefficient (Eta) specific to each complex. This approach has the great advantage to be independent for any calculated BDEs values used as references on the contrary to the model developed by Bayat *et al.*³⁵ Therefore, it does not suffer from the lack of precision that may be encountered with the choice of the theoretical method to calculate thermochemistry data for the reference ion.

<figure><img src="image_6.png" /><figcaption>**Figure 5.** Calculated bond-dissociation energies determined with the 5 theoretical approaches (markers) and linear fit BDE = f(E₀) obtained for each method (colored full lines). The black dotted line indicates the experimentally-determined critical energies and the grey area, the ±2σ error estimated for this value. In **A)**, the whole set of values is displayed, in **B)** and **C)**, the BDEs range < 1.6 eV and > 2.5 eV are zoomed.</figcaption></figure>

The survival yield curves obtained for the 33 complexes are displayed in Fig. 4A. Following the kinetic modeling, a set of 33 critical energies was obtained and is given in Table 1. Two distinct E₀ ranges appear depending on the complex scaffolds: below 1.5 eV for complexes **1** and **2** and above 2.5 eV for complexes **3**. These values agree well with the Au-N<sup>pyrR</sup> bond lengths determined by X-ray diffraction and with the
observation that complexes 3 show a stronger Au-N<sup>pyrR</sup> bonding than the two other series.

<table><caption>**Table 1.** pK<sub>a</sub> values of the free pyridines, E<sub>0</sub> values (eV) measured by HCD-MS and calculated BDE (*M06*) (eV) for the 33 complexes.</caption><thead><tr><th>Complex</th><th>R</th><th>pK<sub>a</sub><sup>a</sup></th><th>E<sub>0</sub><sup>b</sup></th><th>BDE</th></tr></thead><tbody><tr><td>1a</td><td>4-NMe2</td><td>9.71</td><td>1.49 ± 0.14</td><td>1.74</td></tr><tr><td>1b</td><td>4-OMe</td><td>6.55</td><td>1.27 ± 0.12</td><td>1.54</td></tr><tr><td>1c</td><td>4-Me</td><td>6.02</td><td>1.18 ± 0.11</td><td>1.50</td></tr><tr><td>1d</td><td>4-Ph</td><td>5.49</td><td>1.23 ± 0.12</td><td>1.53</td></tr><tr><td>1e</td><td>H</td><td>5.27</td><td>1.12 ± 0.11</td><td>1.41</td></tr><tr><td>1f</td><td>4-Ac</td><td>3.59</td><td>1.01 ± 0.09</td><td>1.33</td></tr><tr><td>1g</td><td>4-CO2Et</td><td>3.45</td><td>1.07 ± 0.10</td><td>1.37</td></tr><tr><td>1h</td><td>4-CF3</td><td>2.46</td><td>0.92 ± 0.09</td><td>1.22</td></tr><tr><td>1i</td><td>4-CN</td><td>1.90</td><td>0.82 ± 0.08</td><td>1.12</td></tr><tr><td>1j</td><td>3-OMe</td><td>4.91</td><td>1.20 ± 0.11</td><td>1.49</td></tr><tr><td>1k</td><td>3-Me</td><td>5.79</td><td>1.22 ± 0.11</td><td>1.48</td></tr><tr><td>1l</td><td>3-CF3</td><td>2.80</td><td>0.94 ± 0.09</td><td>1.21</td></tr><tr><td>1m</td><td>2-OMe</td><td>3.40</td><td>1.09 ± 0.10</td><td>1.39</td></tr><tr><td>1n</td><td>2-Me</td><td>5.97</td><td>1.19 ± 0.11</td><td>1.51</td></tr><tr><td>2a</td><td>4-NMe2</td><td>9.61</td><td>1.34 ± 0.13</td><td>1.76</td></tr><tr><td>2e</td><td>H</td><td>5.23</td><td>1.03 ± 0.10</td><td>1.44</td></tr><tr><td>2f</td><td>4-Ac</td><td>3.57</td><td>0.97 ± 0.09</td><td>1.36</td></tr><tr><td>2h</td><td>4-CF3</td><td>2.46</td><td>0.90 ± 0.08</td><td>1.27</td></tr><tr><td>2i</td><td>4-CN</td><td>2.46</td><td>0.78 ± 0.07</td><td>1.16</td></tr><tr><td>3a</td><td>4-NMe2</td><td>9.61</td><td>3.17 ± 0.32</td><td>3.19</td></tr><tr><td>3b</td><td>4-OMe</td><td>6.47</td><td>3.03 ± 0.30</td><td>2.96</td></tr><tr><td>3c</td><td>4-Me</td><td>5.98</td><td>3.01 ± 0.30</td><td>2.90</td></tr><tr><td>3d</td><td>4-Ph</td><td>5.55</td><td>3.00 ± 0.30</td><td>2.94</td></tr><tr><td>3e</td><td>H</td><td>5.23</td><td>2.98 ± 0.30</td><td>2.80</td></tr><tr><td>3f</td><td>4-Ac</td><td>3.57</td><td>2.84 ± 0.28</td><td>2.71</td></tr><tr><td>3g</td><td>4-CO2Et</td><td>3.45</td><td>2.79 ± 0.28</td><td>2.76</td></tr><tr><td>3h</td><td>4-CF3</td><td>2.46</td><td>2.77 ± 0.28</td><td>2.58</td></tr><tr><td>3i</td><td>4-CN</td><td>2.10</td><td>2.61 ± 0.26</td><td>2.47</td></tr><tr><td>3j</td><td>3-OMe</td><td>4.91</td><td>2.98 ± 0.30</td><td>2.88</td></tr><tr><td>3k</td><td>3-Me</td><td>5.63</td><td>3.00 ± 0.30</td><td>2.87</td></tr><tr><td>3l</td><td>3-CF3</td><td>2.80</td><td>2.82 ± 0.28</td><td>2.56</td></tr><tr><td>3m</td><td>2-OMe</td><td>3.06</td><td>2.88 ± 0.29</td><td>2.73</td></tr><tr><td>3n</td><td>2-Me</td><td>6.00</td><td>3.03 ± 0.30</td><td>2.93</td></tr></tbody></table>

To support and validate our experimental approach, an extensive theoretical work was undertaken. Several DFT approaches were chosen according to literature studies found on similar systems or describing their performance to access BDEs (see SI and ref. 42 for details of the calculations): B3PW91-D3(BJ)/SDD(+f) (Au), 6-31G** (other atoms), TPSSH-D3(BJ)/cc-pVTZ, M06/def2-TZVP and PBE0-D3(BJ)/def2-TZVP. They will be further termed according to the name of the functional

used: B3PW91, TPSSH, M06 and PBE0. Domain-based local pair natural orbital coupled-cluster theory (DLPNO-CCSD(T)/cc-pVTZ termed further DLPNO-CCSD(T)) was also used. BDEs were determined as the 0 K enthalpy change between the fragments and the precursor (including zero-point energy correction).

Comparison of the calculated BDEs with experimental E<sub>0</sub> is provided in Figure 5 and the mean and largest absolute deviations (resp. MAD and LAD), in Table 2 (all calculated values are given in Table S4). Globally, the fits between experiment and theory are quite good (R<sup>2</sup> > 0.97) with a slope of ca. 0.8 for all methods except for B3PW91. Some discrepancies however appear depending on the family of complexes considered. Thus, families 1 and 2 present BDEs with the largest deviation to the E<sub>0</sub> values, with a LAD belonging to the complexes 2 for all theoretical approaches. On the other hand, BDEs of series 3 all fall within the error bar defined for the E<sub>0</sub>. Among all DFT methods, the M06 functional appears to provide the closest BDEs values to experiment with a MAD of 5.2 kcal/mol. Conversely, the DLPNO-CCSD(T) method exhibit results with a larger deviation (MAD of 9.6 kcal/mol). The non-negligible deviation of this approach for the determination of BDEs in transition-metal complexes has already been several times reported. In particular, Husch et al. also related similar divergence to experiment with DLPNO-CCSD(T).<sup>43</sup> By comparing the performance of various theoretical approaches for a various set of organometallics reactions, they for instance found a MAD larger than 18 kcal/mol for an Au(I) system. Validity of the theoretical approaches is difficult to assess because of the very large difference and performance reported in the literature. Altogether, the calculated BDEs however predict the same trend as experiment and are consistent together. In particular, the PBE0, TPSSH and DLPNO-CCSD(T) methods present very close agreement.

To summarize, a global shift of about 0.3 eV (7 kcal/mol) is obtained between theory and experiment. The largest deviation to theory is obtained for complexes 1 and 2, although they are the experimental data obtained with the highest precision (see Fig. 4B), C) and D)). A possible explanation for this shift is related to the choice of the transition states (TS). A TS treated at the phase space limit (PSL) may have been relevant and would have probably produce higher values of E<sub>0</sub>, this TS being product-like.<sup>44</sup> However this approach is not available in MassKinetics software. On the other hand, the calculated BDEs also appear to be overestimated. For instance, the calculated BDEs for 1i vary between 1.12 eV and 1.53 eV depending on the methods used which seems high considering that this compound is decomposed at 63% for a collision voltage of 5 V. In the case of family 3, the modeling of the curves was more complex due to consecutive and competitive fragmentations with the most abundant fragment being not always the pyridine loss. Despite this shift, the correlation experiment/theory remains very satisfying and help comforting the validity of our kinetic model.

To follow up on the evaluation of the ligand influence on the Au-N<sup>pyrR</sup> bond strength, we compared the determined critical energies with the pK<sub>a</sub> of the corresponding free pyridines (Figure 6). Very interestingly, an almost-linear dependence with the pK<sub>a</sub>s appeared for the three scaffolds together (R<sup>2</sup> > 0.88). This indicates that the critical energies can be directly related to the donating capability of the pyridine and do not depend on the substituent position on the pyridine. They can be applied over a large range of bonding strength, from the most fragile complexes 1 and 2 up to the strongest ones, complexes 3. This

<footnote><sup>a</sup> Experimental or calculated pKa were obtained from ref. 37 (pyridines a, e, k), ref. 38 (pyridines b, c, g, j, m, n), ref. 39 (pyridine d), ref. 40 (pyridines f, i), ref. 32 (pyridine h) and ref. 41 (pyridine l). <sup>b</sup> The uncertainties given here correspond to 1 σ and were estimated by varying the different parameters used in the kinetic model (see SI for details).</footnote>
<table><caption>**Table 2.** Mean and largest absolute deviations (resp., MAD and LAD in kcal/mol) to E₀ obtained for the 5 theoretical methods used. The data are given for the whole set of complexes and for each series. The equation of the linear fit BDE = f(E₀) (in eV) displayed in Fig. 5 and the determination coefficient are also given.</caption><thead><tr><th rowspan="2"></th><th colspan="4">MAD (LAD)</th><th rowspan="2">Equation of the fit<br>y = ax + b (R<sup>2</sup>)</th></tr><tr><th>1</th><th>2</th><th>3</th><th>All</th></tr></thead><tbody><tr><td><b>B3PW91</b></td><td>8.5 (10.1)</td><td>14.4 (15.4)</td><td>2.4 (9.1)</td><td>6.8</td><td>y = 0.712x + 0.74705 (R<sup>2</sup> = 0.9693)</td></tr><tr><td><b>TPSSH</b></td><td>12.9 (13.5)</td><td>17.5 (18.5)</td><td>3.8 (7.3)</td><td>19.8</td><td>y = 0.763x + 0.8678 (R<sup>2</sup> = 0.9833)</td></tr><tr><td><b>M06</b></td><td>6.2 (7.3)</td><td>9.1 (9.6)</td><td>2.8 (6.0)</td><td>5.2</td><td>y = 0.770x + 0.5643 (R<sup>2</sup> = 0.9901)</td></tr><tr><td><b>PBE0</b></td><td>12.7 (13.3)</td><td>16.2 (17.2)</td><td>4.3 (7.9)</td><td>9.7</td><td>y = 0.786x + 0.82068 (R<sup>2</sup> = 0.9879)</td></tr><tr><td><b>DLPNO-CCSD(T)</b></td><td>12.4 (13.2)</td><td>15.8 (16.5)</td><td>4.6 (8.1)</td><td>9.6</td><td>y = 0.801x + 0.79026 (R<sup>2</sup> = 0.9897)</td></tr></tbody></table>

underline the more global character of this descriptor in contrast with the ¹H NMR chemical shift analysis which could only provide reliable results for a restrained range of Au-pyrR interaction (same scaffold). Moreover, for the three families of complexes, the differences between the most stable and the most fragile complexes are rather equivalent: ca 0.6 eV for the three series. This suggests that the substituents on the pyridine have similar impact of the Au-pyrR bond whatever the considered Au(III) scaffold. Furthermore, the difference observed between the [(C^C)Au(NHC)(pyrR)]⁺ and [(C^N^C)Au(pyrR)]⁺ complexes remains constant for each pyridine with an average value of 1.80 eV. This value can be seen as a quantification by means of bond strength of the difference in the *trans* influence of an aryl group and a N-donor group. One can also further notice that the replacement of the NHC ligand by a PPh₃ is leading to slightly lower E₀ values which can be attributed to a greater sterical hindrance of the PPh₃ ligand when compared to the NHC, thus weakening the bonding between the pyridine and the metal (families 1 and 2, Fig. 6). The magnitude of this decrease appeared very dependent of the pyridine ligand with the most electron-rich pyridine being the most impacted by this effect (ΔE₀ = -0.15, -0.09 and -0.04 eV between 1a and 2a, 1e and 2e and 1i and 2i, respectively). One can tentatively rationalize these results considering the π-stacking observed in the crystal structures of [(C^C)Au(PPh₃)(pyrR)]⁺ complexes between the pyridines and a phenyl ring of the PPh₃ ligand. This interaction is stronger with electron-poor pyridine ligands and partially compensates the steric hindrance of the PPh₃ in good agreement with the greater downfield shift of the ¹H NMR signals observed for complexes 2fPF₆, 2hPF₆ and 2iPF₆ (figure 4B,C).

<figure><img src="image_7.png" /><figcaption>**Figure 6.** Relation between the critical energies determined for the 33 Au(III) complexes (± 1σ) and the pKₐ of the corresponding free pyridines.</figcaption></figure>

These results are also in good agreement with the results obtained for Au-N<sup>pyrR</sup> distances measured by X-ray diffraction analysis (Fig. 3, Table 1) for which we observed a clear

discrimination due to the *trans* influence of the scaffold but not between the [(C^C)Au(NHC)(pyrR)]⁺ and [(C^C)Au(PPh₃)(pyrR)]⁺ complexes or between the members of a given family. Combined together, these results enable us to decompose the various contributions of the different part of the complexes into the Au-pyridine dissociation energy: the main contribution comes from *trans* influence of the chelating ligand as was observed for Au(III)-H complexes,⁷ then comes the substituent effect on the pyridine ligands and finally comes the impact of the *cis* ligand.

**π-backdonation investigation.** In the literature, the π-backdonation contribution in gold (I/III) complexes remains a debated topic.⁴⁵,⁴⁶ In Au(I) complexes, theoretical studies have suggested important contribution of π-backdonation in the Au-C bond strength in acetylene,⁴⁷ CO⁴⁸ and NHC⁴⁹ complexes. However, most of the time, no experimental observation of this π-backdonation could be made.⁴⁸,⁵⁰ Bourissou reported one of the sole experimental example of an Au(I) complex exerting π-backdonation by using a trigonal Au(I) scaffold with a chelating diphosphine ligand.⁵¹ Furthermore, isolobality between cationic Au(I) and proton has already been stated⁵² and points thus toward the poor contribution of π-backdonation in gold(I) complexes. A similar analogy is missing for Au(III) complexes although it could bring valuable information on the involvement of π-backdonation in Au(III) chemistry. Theoretical studies pointed to the involvement of π-backdonation in Au(III)-CO and alkyne bonds,⁵³⁻⁵⁵ however, due the low stability of Au(III)-CO and alkyne complexes, very few Au(III) carbonyl or alkyne complexes are reported so far,⁷,⁵⁶,⁵⁷ and thus investigation of π-backdonation in Au(III) complexes are scarce. Whereas variably reliable or no correlation could be observed between pKₐ and ¹H NMR data and the Au-N<sup>pyrR</sup> bond length, a reliable linear correlation was evidenced for the three scaffolds by considering the Au-N<sup>pyrR</sup> E₀ with very similar slopes observed for the corresponding linear regression curves. These results indicate an analogous behavior of the cationic Au(III) scaffolds towards coordination with pyridines and this may suggest the isolobality of these three cationic organogold(III) scaffolds with protons. To investigate in more detail this feature, a closer look was taken on the Au-N<sup>pyrR</sup> interaction by using an energy decomposition analysis (EDA). This theoretical approach enables a quantitative description and decomposition of the various energetics terms involved in the bonding between two fragments, the Au(III) scaffold and the pyridine here. These terms are the global interaction energy ΔE<sub>int</sub> which is decomposed into a repulsive (Pauli repulsion, ΔE<sub>Pauli</sub>) and two attractive terms responsible for the electrostatic (ΔE<sub>elect</sub>) and the orbital (ΔE<sub>orb</sub>) interaction. They are displayed in Fig. S25 vs. the critical energy E₀ of the complexes and the values are given in the SI (Table
S8). All four terms have an almost linear dependence towards the BDEs. The interaction energy is predicted larger for the complexes 3 in agreement with the measured E0s and BDEs. For the three series, the contribution of the electrostatic attraction in the total attractive interactions for the Au(III) complexes is larger (ca 65%) than the covalent (orbital) ΔE<sub>orb</sub> binding (ca 35%). This results agrees well with previous theoretical work of Radenković et al. on Au–N bonding in Au(III) complexes.<sup>58,64</sup> Using various theoretical approaches, they indeed determined that the bonding between Au(III) and N-containing heterocycles has a higher electrostatic than covalent character.

<figure><img src="image_8.png" /><figcaption>**Figure 7.** Contours of deformation density Δρ<sub>σ</sub> and Δρ<sub>π</sub> connected with the pairs of interacting orbitals in the **1e**, **2e** and **3e** complexes. The surfaces in light purple represent an electron density loss and in dark blue, an electron density gain. The associated orbital interaction energies ΔE<sub>orb</sub> are given in kcal/mol, v is the eigenvalue indicating the size of the charge flow. Isosurface value: 0.0025 a.u.</figcaption></figure>

The ΔE<sub>orb</sub> contribution can be further decomposed using the NOCV approach (natural orbitals for chemical valence). This enables to obtain the main deformation densities contributing to the orbital interaction on the Au-N<sup>pyrR</sup> bond. For each family of complexes, an example of the NOCV results is displayed in Fig. 7 and the results for all complexes in Table S9. Two main contributions accounting for more than 80% are observed, showing that the Au-N<sup>pyrR</sup> bonding exhibits mostly a σ-donor and a π-acceptor character (Δρ<sub>σ</sub> and Δρ<sub>π</sub>, ca 70% and 10% of the contribution, respectively). Altogether, these results point toward a limited involvement of the π-backdonation in good agreement with the similar linear correlation between the E0s of the complexes for the three families and the pK<sub>as</sub> of the pyridines.

**Application to catalysis.** As seen, the donating capability of the pyridines described by their pK<sub>as</sub> exhibits a close dependence to the Au-N<sup>pyrR</sup> bond dissociation energies. In a further step, we wished to confront these results with a catalytic application to determine in which extent the ligand donor effect may be related to catalytic efficiency of the corresponding complexes. We focused on the well-known Lewis acid properties of gold complexes which can thus act as catalysts to activate C-C multiple bonds toward nucleophilic attacks.<sup>59, 60</sup> In particular, Toste has reported the use of a [(C^C)Au(NHC)]<sup>+</sup> cation (generated by chloride abstraction from the corresponding

[(C^C)Au(NHC)Cl] complex) for an enantiocovergent cycloisomerization reaction of enynes.<sup>61</sup> Moreover, 8-hydroxyjuloludinyl phenylpropiolate has been reported to be efficiently converted to the corresponding coumarin *via* a gold-catalyzed intramolecular hydroarylation reaction.<sup>62, 63</sup> Within this context, we decided to apply our Au(III)-pyridine complexes in the intramolecular hydroarylation reaction of 8-hydroxyjuloludinyl phenylpropiolate (Fig. 8A)). We reacted the substrate with 2.5 mol% of Au(III) complexes in CDCl<sub>3</sub> at room temperature for 6 h and calculated the conversion rate using <sup>1</sup>H NMR spectroscopy. Considering that the decoordination of the pyridine ligands would generate the catalytically active species similar to Toste's systems, we correlated the conversion rate of the reaction with the dissociation energies we measured for the complexes (Fig. 8 and table S10).

<figure><img src="image_9.png" /><figcaption>**Figure 8.** A) Conversion reaction scheme of 8-hydroxyjuloludinyl phenylpropiolate catalyzed by the studied Au(III) complexes and B) relation between the determined <sup>1</sup>H NMR conversion of the reaction (%) and the critical energies of the Au(III) complexes.</figcaption></figure>

For the (C^C)-based complexes **1a-n** and **2a, e, f, h, i**, a correlation between the dissociation energy of the pyridine ligand and the conversion rate is observed. In both cases, the conversion rate is indeed increasing when the dissociation energy decreases. In the series of complexes **1a-n**, the conversion rate evolves from almost no conversion for the most stable complex (0.8 % conversion for complex **1a**) to almost complete conversion for the complex with the most labile pyridine ligand (99 % conversion for complex **1i**). The same trend is observed in the complexes **2** series with the most stable complex **2a** giving only 1.1 % conversion and complex **2i**, with the most labile pyridine ligand, leading to 70 % conversion. Within each family of complexes, the same catalytically active species is formed upon decoordination of the pyridine ligands, ie. [(C^C)Au(NHC)]<sup>+</sup> and [(C^C)Au(PPh<sub>3</sub>)]<sup>+</sup> for complexes **1a-n** and **2a, e, f, h, i**, respectively. As such, the more labile the pyridine is, the more the catalytically active species is generated leading to a higher conversion rate. For the (C^N^C)-based complexes, none of them showed any catalytic activity independently to the nature of the pyridine ligand suggesting that all are too stable to generate the catalytically active species. This is consistent with the determined E0s showing that all (C^N^C)-based complexes are much more stable than all (C^C)-based ones. The dissociation energy between the pyridine ligand and Au(III) appears thus to be a key parameter for the conversion of the substrate as it enables the generation of the catalytically active species. Furthermore, it is worth noting that despite slightly lower dissociation energies of the pyridine ligands in the [(C^C)Au(PPh<sub>3</sub>)(pyrR)]<sup>+</sup> series compared to the [(C^C)Au(NHC)(pyrR)]<sup>+</sup> analogues, complexes [(C^C)Au(PPh<sub>3</sub>)(pyrR)]<sup>+</sup> lead to lower conversion rates (conversion rates of 70, 31 and 2.5 % for **2i**, **2h** and **2f**, respectively
compared to 99, 88 and 31 % for 1i, 1h and 1f, respectively). This shows that the conversion rate is influenced by other parameters than the dissociation energies. After decoordination of the pyridines, the formed catalytically active species may exhibit different efficiencies leading thus to different reaction yields. In this particular case, the [(C^C)Au(NHC)]^+ species appears more efficient than the [(C^C)Au(PPh3)]^+ analog. We compared the geometry optimized structures of the [(C^C)Au(NHC)]^+ and [(C^C)Au(PPh3)]^+ scaffolds. Interestingly, a large difference is observed in the access angle of the substrate to the Au(III) center due to the larger steric influence of PPh3 compared to the planar NHC (resp. 10° vs. 113°, Fig. S27). As such, although electronic differences between the two active species should not be ruled out, steric hindrance around the gold center in the active species seems to be the discriminating parameter. Indeed, the coordination of the C-C triple bond to the Au(III) center which is the first step of the catalytic cycle (Fig. S27C)), might be disfavored in the case of the [(C^C)Au(PPh3)]^+ species leading to a reduced conversion of the substrate. This feature illustrates the role that steric effect may play in complement to pure electronic influence of the ligand.

## CONCLUSIONS

We report in this work the synthesis of 33 new organogold complexes based on three different scaffolds [(C^C)Au(NHC)(pyrR)]^+, [(C^C)Au(PPh3)(pyrR)]^+ and [(C^N^C)Au(pyrR)]^+. These complexes have been used for the development of a first direct and absolute experimental methodology for the determination of metal-ligand dissociation energies using an HCD-based mass spectrometry approach over a large dissociation energy range. Confrontation of the results with several theoretical methods demonstrate the high reliability of the results obtained and the ability of this approach to describe simultaneously very different systems by means of sizes and strengths, on the contrary to classical methodologies based on NMR spectroscopy and crystal structure analysis. Further analysis on the Au-pyrR interaction using the EDA scheme could demonstrate a low contribution of the π-backdonation for all systems and thus the isolobality of the different Au(III) scaffolds with proton. Additionally, the catalytic activity of the complexes was determined in an alkyne intramolecular hydroarylation reaction. Rationalizing the results in light of the complexes critical energies could help to discriminate the systems limited by the activation of the pre-catalyst from the systems limited by the reactivity of the catalytic species. Altogether, these data highlight the great potential of this gas-phase methodology and of the metal-ligand dissociation energy as a reliable ligand effect descriptor. It could help to access a better comprehension of the intramolecular interactions and of the condensed-phase activity of organometallics. Furthermore, if the proposed methodology requires specific instruments and kinetic modelization tools, relative M-L bond strengths can be easily accessed with a good precision from simplified MS analysis (E₁/₂) or by theory, enabling thus an universal access to the methodology.

## ASSOCIATED CONTENT

### Supporting Information

The Supporting Information is available free of charge on the ACS Publications website.
Supplementary Informations_final.pdf

## AUTHOR INFORMATION

### Corresponding Authors

* Denis Lesage: Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM UMR 8232), F-75005 Paris, France
Email: denis.lesage@sorbonne-universite.fr

* Benoît Bertrand: Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM UMR 8232), F-75005 Paris, France
Email: benoit.bertrand@sorbonne-universite.fr

* Héloïse Dossmann: Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM UMR 8232), F-75005 Paris, France
Email: heloise.dossmann@sorbonne-universite.fr

### Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

## ACKNOWLEDGMENT

This work was granted access to the HPC resources of the SACADO MeSU platform at Sorbonne Université, HD, BB and DL thanks CNRS and Sorbonne Université for financial support, LB thanks the Labex MiChem and the SOLEIL synchrotron facility for PhD funding. SS grateful acknowledged Erasmus+ for a traineeship funding.

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