Pt(II) Derivatives with Rollover-Coordinated 6-substituted 2, 2′ -bipyridines: Ligands with Multiple Personalities

Featured Applications: The new rollover complexes and the study of their reactivity could have various potential applications such as photo-responsive devices, antitumor agents, and catalytic processes (e.g., hydrogen transfer reactions). Abstract: We report here the synthesis, characterization and behavior of a series of Pt(II) cyclometalated rollover complexes with two substituted bipyridines, 6-ethyl-2, 2′ -bipyridine (bpy 6Et ) and 6-methoxy-2, 2′ -bipyridine (bpy 6OMe ), in comparison with previously studied 2, 2′ -bipyridine complexes. The two ligands have similar steric hindrance but different electronic properties. As a result, the reactivity of the two series of complexes follows very different routes. In particular, the new complexes behave differently towards protonation reactions, differences given by substituents and ancillary ligands, added to the presence of several nucleophilic centers. Reaction of complex [Pt(bpy 6OMe -H)(PPh 3 )Me)] with [H 3 O ⋅ 18-crown-6][BF 4 ] results in a retro-rollover reaction whose final product is the cationic adduct [Pt(bpy 6OMe )(PPh 3 )Me)] + . Surprisingly, only the isomer with the cis -PPh 3 -OMe geometry is formed; in spite of an expected instability due to steric hindrance, Density-Functional theory (DFT) calculations showed that this isomer is the most stable. This result shows that the cone angle is far fro m being a real “solid cone” and should lead to a different interpretation of well-known concepts concerning steric bulk of ligands, such as cone angle. Proton affinity values of ligands, neutral complexes and their protonated counterparts were analyzed by means of DFT calculations, allowing a comparison of their properties.


Introduction
Cyclometalated complexes constitute an important class of organometallic compounds owing to their intrinsic stability and the wide range of their potential applications [1][2][3]. Among the ample variety of cyclometalated compounds, the so-called rollover complexes constitute a special and intriguing case due to their peculiar properties [4][5][6].
The differences between the classical and rollover cyclometalated compounds at a first sight may appear trivial; however, they are, as a matter of fact, substantial. The first difference which connotes the rollover subclass resides in the C-H bond activation process which generates the complexes: classical cyclometallation needs simple coordination of a monodentate ligand, followed by C-H bond activation and metalation; at variance, the rollover process needs a bidentate heterocyclic ligand, which may "choose" between a classical chelation or cyclometallation (see Scheme 1). Usually the first act is the formation of a chelated complex, followed by decoordination of one of the donor atoms, internal rotation of the heteroaromatic rings and, finally, a "remote" C-H bond activation (Scheme 1) [7,8]. As reported by Skapski, Sutcliffe and Young in their precursor work on rollover cyclometalation (where they coined the term "roll-over cyclometalation") [7], metalation is faster for Pt(II) electronrich starting complexes. An oxidative addition of the C(3)-H bond followed by reductive elimination of methane is a likely reaction pathway. Scheme 1. Rollover cyclometalation of 6-substituted 2,2′-bipyridines with by Pt(II).
2-Phenylpyridine and 2,2′-bipyridine are common examples of ligands able to give classical and rollover cyclometalated complexes, as depicted in Figure 1.
A first consequence of the difference between the two classes of organometallic species is that the rollover process is reversible in nature by means of protonation, leading to noteworthy applications, e.g., in catalysis [9][10][11][12][13][14][15][16][17][18][19]. A second important difference between the two subclasses is given by the uncoordinated donor atom, usually a nitrogen, able to act as a Lewis base and hence influence the reactivity and properties of the complex, by means of coordination, protonation, interactions and, as stated above, reversibility of the rollover process. For such reasons, these "rollover" ligands belong to the interesting category of "ligands with multiple personalities" [20]. Protonation of the uncoordinated nitrogen transforms the rollover-cyclometalated 2,2′-bipyridine, formally an anionic ligand, into a neutral mesoionic ligand, an abnormal-remote pyridylene ligand [21][22][23][24][25]. DFT calculations were carried out using the PBE0 hybrid functional developed by Perdew, Burke and Ernzerhof [56,57] and modified in its hybrid version by Adamo and Barone [58] with ZORA (Zeroth order regular approximation) [59][60][61][62] using the ZORA-def2-SVP basis set for all atoms except for Pt for which we used a segmented all-electron relativistically contracted (SARC) basis set [63] along with the RI-JONX approximation as implemented in the ORCA 4.2.1 package [64,65]. Harmonic analysis at the same level of theory was carried out on the equilibrium geometries to confirm the nature of the minimum (i.e., the absence of imaginary frequencies) on the PES (Potential energy surface).

Preparations
Compounds 1a and 6a were prepared as described in reference [66].

Reaction between 1a, [Pt(bpy 6OMe -H)(Me)DMSO], and [H3O⋅18-crown-6][BF4]
The reaction between 1a and [H3O⋅18-crown-6] [BF4] was performed under the same conditions of the analogous reaction of complex 1b. The reaction was also followed by means of 1 H NMR. Despite several attempts, we were not able to identify the reaction products, with the exception of a singlet at 0.17 ppm (acetone d6), attributed to free methane.

Stereoelectronic Properties of Substituted 2,2′-bipyridines
The coordinative behavior of substituted bipyridines is strictly dependent on the electronic and steric properties given by their substituents. In the particular case of rollover cyclometallation, two points should be considered: coordination/decoordination of the labile nitrogen donor atom, and activation of a remote C-H bond.
It is generally agreed that after chelation, the first step of the process is nitrogen detachment (see Scheme 1), therefore a weaker M-N bond will facilitate the rollover reaction; in contrast, good donor nitrogen atoms will stabilize chelated adducts and contrast rollover metalation. A weak M-N bond can be achieved electronically, by reducing the electron density at the nitrogen (e.g., introducing an electron-withdrawing substituent in the ring), or sterically, employing a bulky substituent in proximity of the nitrogen atom [8].
The last step of the process, i.e., the remote C-H bond activation (see Scheme 1, from D to E), in the case of platinum (II) likely involves a nucleophilic behavior of the metal [7,8]; in this case, electron withdrawing groups are expected to facilitate the process.
Owing to these considerations, the CF3 substituent in 6-CF3-2,2′-bipyridine (bpy 6CF3 ) favors all of these steps, decreasing the electronic density of the nearby nitrogen, increasing the steric congestion around it and activating the C(3)-H bond towards nucleophilic attack of the metal. As a consequence, rollover cyclometalation of bpy 6CF3 is very fast even at room temperature [67]. It is also worth noting that starting from electron-rich Pt(II) complexes, such as [PtMe2(DMSO)2], the process is irreversible due to methane formation, so kinetic factors will rule the reaction outcome.
Evaluation of the donor capabilities of the nitrogen atoms in 2,2′-bipyridines may be extrapolated by analyzing proton affinity and basicity data of the corresponding substituted pyridines and pyridinium ions (see Table 1). (Proton affinity and basicity values in the gas phase (KJ/mol) of substituted pyridines and pKa data of substituted pyridinium ions in solution. ζ angle (°) for 6-R-2,2′-bipyridines [68][69][70]. a Pyridine numbering; bipyridine numbering in parentheses. Table 1 confirms that methyl and ethyl substituents have a marked electrondonor effect in all positions, although to a smaller extent in position 3, while the opposite is true for CF3. In contrast, the methoxy substituent is not so straightforward in its contribution, having inductive electron withdrawing effect (-I effect) but mesomeric electron donating effect (+M effect) [71]. In the gas phase, proton affinity of methoxypyridines is only slightly higher than that of pyridine, but in solution the pKa values show that 2-methoxy-pyridine is a worse donor with respect to pyridine by two pKa units (pKa = 3.1-3.2 vs. 5.2), likely due to solvation effects.

Data reported in
In contrast, the pKa value of 4-methoxy-pyridinium ion (6.62) shows that a methoxy substituent in the para position makes the nitrogen a better σ-donor. This value suggests that for a MeO-group in the para position, the mesomeric effect is predominant (the nitrogen is more basic and electron-rich than that in 4-Me-pyridine). By extrapolation, a para C-H bond will have a higher electron density and will be less prone to electrophilic activation.
A second important element in rollover metalation is given by steric factors, which play a significant role in the regioselectivity of the process. It should be noted that in 6-substituted bipyridines, only the substituted pyridine ring undergoes C-H activation, both with 6-CH3 and with 6-CF3 substituents. Only in 5-substitued 2,2′-bipyridines a different behavior of the substituted and unsubstituted ring has been reported [51].
Previous data show an acceleration of the process due to the bulkiness of the substituent (e.g., 6-tert-butyl-2,2′-bipyridine vs. 6-Me-bipyridine [51]). With the intention to measure the steric contribution to the reaction, we have recently reported the ζ angle of substituted bipyridines [51], which evaluated the steric hindrance of a bipyridine ligand.
The angle ζ is defined as the angle between the bisector of the N−Pt−N angle and the tangent to the remotest van der Waals surface of the substituent, passing through the metal center, as depicted in Figure 2 for [Pt(bpy 6Me )(CH3)2]. These data show that unsubstituted 2,2′-bipyridine occupies only 8.8° above the theoretical 90° available for a square planar configuration. A methyl substituent in position 6, with a ζ angle of ca 125° exceeds the available space by 35°. For the two ligands compared in this paper, bpy 6Et and bpy 6OMe , it is possible to identify a minimum and a maximum angle due to substituent flexibility, whereas the maximum is similar for both the ligands (157° vs. 152°, respectively) and the minimum hindrance of bpy 6OMe is definitely smaller (109° vs. 125°).
Putting together all these data, it is expected that, in comparison with the unsubstituted 2,2′bipyridine, 6-ethyl-2,2′-bipyridine, bpy 6Et possesses a better nitrogen donor in the substituted ring, whereas bpy 6OMe has a less basic one. Both the substituted ligands are expected to have a favorable detachment of the second nitrogen (first act of the rollover process: from A to B in Scheme 1) for steric reasons (bpy 6Et favored in respect to bpy 6OMe ) whereas bpy 6OMe will decoordinate easily the nitrogen donor due to its electronic properties.
As for the remote C-H bond activation, (Scheme 1, from B to C) bpy 6Et will be favored, with the ethyl substituent being a worst electron-donor in the para position than the methoxy one.
Putting together all these data it may be expected that bpy 6Et and bpy 6OMe may possess a similar steric hindrance but clearly different electronic properties.
Furthermore, it is worth reminding that the nature of the substituent will also have influence on the reactivity of corresponding rollover species, and the investigation of this effect is the second scope of this research work.

Synthesis and Characterization
In our experience, the best starting complex for Pt(II) rollover cyclometallation is the electronrich derivative [PtMe2(DMSO)2]. With this starting complex, the reaction proceeds even at room temperature for both ligands studied in this paper. In order to obtain reasonable conversions, the syntheses may be optimized operating in acetone at 40-50 °C to give the rollover complexes Activation of bpy 6OMe has been recently reported by some of us [66] and occurs easily, whereas activation of bpy 6Et proceeds slowly at room temperature. Bpy 6Et has a slightly greater steric hindrance than bpy 6OMe , hence the easier C-H bond activation in bpy 6OMe should not be ascribed to steric factors but may be due to the scarce donor ability of the nitrogen atom close to the OMe substituent.
The rollover metalation is clearly confirmed, in the 1 H NMR spectrum, by (i) the absence of the H3 proton; (ii) the AB system with satellites given by the remaining H4 and H5 protons in the substituted pyridine ring; (iii) coordination of the Me and DMSO ligands (confirmed by 195 Pt satellites), (iv) coordination shift and 195 Pt satellites of the H6′ proton.
In order to evaluate differences in the properties of rollover complexes due to the substituent, we compared the NMR data of a series of substituted 2,2′-bipyridines obtained in our laboratory (6-R-2,2′-bpy, R=OMe, Et, Me, CH3, CF3, Ph, H). Comparison of 1 H NMR data of complexes 1a-1e (Table  2) shows, in general, minor differences. An interesting trend is displayed by the H4 proton, whose coupling constant with 195 Pt ( 3 J( 195 Pt-H4)) increases with the electron-withdrawing ability of the substituent (50, 53, 54 and 56 Hz, for bpy 6OMe , bpy 6Me , bpy and bpy 6CF3, respectively). Even though several factors should be considered, it is likely that the Pt-C(3) bond is stronger for less electron-rich heteroaromatic rings.  (14) 8.01 (54) The organometallic behavior of 6-substituted 2,2′-bipyridines may be complex as several C-H bonds can be activated [49,72]. In particular, also activation of the substituent can occur, to give a terdentate N,N,C cyclometalated complex. C-H bond activation of the C(3)-H and the substituent are in competition, especially when a 5-or 6-membered N,C cycle can be formed. The regioselectivity of the processes depends on several factors; sometimes even small changes in the structure of the ligand or in the reaction conditions can lead the reaction towards unexpected results. It seems, however, that in the case of Pt(II), electron-rich starting complexes strongly prefer the rollover process.
In order to evaluate different electronic properties ascribable to the substituent, the electrochemical behavior and electronic properties of compounds 1a and 1b were investigated by cyclic voltammetry and UV spectroscopy, respectively. The electrochemical behavior of both complexes was investigated in TEAPF6/CH2Cl2 solvent system, at a potential scan rate equal to 100 mV s −1 . No cathodic process is evidenced in the experimental conditions.
The voltammetric response of 1a shows an anodic, irreversible process located at 1.29 V ( Figure  3). The evaluation of the onset potential allowed the determination of the energy value of HOMO (highest occupied molecular orbital) (−5.59 eV). The comparison with literature data [74] suggests that the anodic process is due to a mono-electronic EC (electrochemical-chemical) transfer. The main reason for the irreversibility of the process is the instability of the formally Pt(III) derivative. Indeed, usually anodic process on Pt(II) derivatives are attributed mainly to the metal center [75]. Nevertheless, according to our previous evaluation on the parent derivative [Pt(bpy-H)(Me)DMSO)] 1e [76], we can hypothesize that the anodic process involves mainly the bpy ligand and, to a minor extent, the metal center.
The voltammetric response of 1b (Figure 3) shows an irreversible, broad anodic process located at more positive potential values (between 1.4 V and 1.5 V), characterized by an evidently poor reproducibility. As a consequence, in the case of 1b it is possible to approximately estimate the energy of the HOMO (about −5.4 eV).
The scarce reproducibility of the response of 1b does not allow accurate comparison between the two complexes and the parent unsubstituted-bpy derivative. In either case, we can observe ( Table  3) that the bpy 6Et cyclometalated complex appears more stable than the corresponding bpy 6OMe derivative, which in turn is more stable than the bpy one.
A comparison between the HOMO values of the parent species 1e and the derivative 1b confirms that the presence of the −Et substituent on the bpy ligand induces a stabilization of the HOMO. Despite the trend observed in anodic potential values, the HOMO in 1a is lower in energy than in 1b and in 1e. Such apparently anomalous behavior can be ascribed to the mixed -I/+M electron effect of the -OMe substituent.
The UV-Vis spectra in CH2Cl2 ( Figure 3 and Table 3) is evidence of the presence of higher energy bands, attributed to ligand-centered transitions (p→p*) located on the bpy 6R ligand. Furthermore, dPt →p* metal-to-ligand charge transfer mixed with intra-ligand transitions are present at lower energy. In addition, a blue shift in the MLCT (metal to ligand charge transfer) band going from bpy to bpy 6OMe to bpy 6Et is observed, suggesting an increasing s-donor effect according to this trend.
Finally, the energy gap values (Eg,opt) were calculated from the UV-Vis spectra, showing an increasing trend along the series 1b > 1a > 1e. The LUMO energies obtained from the experimental Eg,opt and HOMO values [77] suggest that the increasing in Eg,opt is due to a stabilization both of the highest occupied and of the lower unoccupied molecular orbitals. The frontier orbitals of the investigated compounds are depicted in Figure 4. Within the same series (e.g., HOMO for 1a-e) both the HOMO and LUMO are qualitatively similar. The HOMO of protonated species 3a-e (see later) is mainly localized on the platinum atom.

Reactivity with Acids
One of the most important features of rollover complexes derived from 2,2′-bipyridines is the presence of an uncoordinated nitrogen atom, able to act as a Lewis base. As reported by us and by other groups [37,78,79], the reactivity of Pt(II) rollover complexes with electrophiles may be complex, due to the presence of several centers able to act as nucleophiles: the uncoordinated nitrogen, the electron-rich platinum center, and the two Pt-C bonds.
In the case of nitrogen protonation, the resulting neutral bipyridine ligand, reported in this paper as bpy*, is an isomer of the corresponding bipyridine, and should be considered either as a mesoionic ligand or an abnormal remote carbene, being a 3-pyridylene ligand ( Figure 5) [21][22][23][24][25]. Two different situations were studied: reaction with a strong acid bearing a weakly coordinating anion, [H3O⋅18-crown-6] [BF4], and reaction with HCl, having, at variance, a strongly coordinating anion. As expected, the reaction proceeded differently in the two cases, also depending on the nature of the neutral and anionic ligands (PPh3 vs. DMSO and Me vs. Cl) as well as the substituent of the bipyridine ligand.
The protonation reactions were performed under mild conditions, e.g., acetone at room temperature.
The behavior towards acids of complexes 1a and 1b is very different. Complex 1b is easily protonated at the free nitrogen to give the stable cationic pyridylene complex [Pt(bpy 6Et *)(Me)(DMSO)] + , 3b, which can be isolated in the solid state as its BF4 salt 3b-BF4 ( Figure 6). The neutral ligand bpy 6Et * is both a mesoionic isomer of free bpy 6Et and an abnormal 3-pyridylene [21][22][23][24][25]. This behavior brings rollover-cyclometalated 6-ethyl-2,2′-bipyridine ligand into the class of "ligands with multiple personalities", i.e., ligands that, far from being simple spectators in reactions, can enhance or modify the reactivity of the metal center after protonation, deprotonation or other simple acts [20].
This easy protonation is likely due to the good basicity of the uncoordinated nitrogen atom and to a not excessive electron density on the Pt atom. The Pt-C(sp 2 ) and Pt-C(sp 3 ) bonds appear to be fairly stable under these conditions.
In contrast, no signs of protonation were detected in the reaction of complex 1a. The reaction was also followed by means of 1 H NMR spectroscopy, observing rapid liberation of methane (a singlet at 0.18 ppm) and no signs of N-H protons. The Pt-CH3 signal disappears with the appearance of methane. The spectra showed the presence of several species in solution which we were not able to identify. Even isolation in the solid state of the reaction products did not allow us to characterize the formed species. It seems, overall, that in the case of complex 1a, electrophilic attack occurs on the Pt center or on the Pt-CH3 bond. The resulting liberation of methane leads to unstable species and, finally, to decomposition.
The different behavior of the two bipyridine ligands is likely due to the scarce basicity of the uncoordinated nitrogen in bpy 6OMe combined to a higher electron density on the Pt center. In addition, the planar configuration induced by metalation reduces the availability of the nitrogen lone pair due to the proximity of the C(3′)-H hydrogen.
The reaction of complexes 1a-b with HCl is different from that with [H3O⋅18-crown-6][BF4]. It is worth noting that in this case 1a and 1b react in the same way, leading to methane elimination and formation of the corresponding chloride derivatives [Pt(bpy 6R -H)Cl(DMSO)] (R = OMe, 4a; R = Et, 4b), which can be isolated with good yields and characterized.
The reaction process can be simplified following a "one pot" procedure, reacting [Pt(DMSO)2Me2] with bpy 6R at 50 °C and adding HCl after the rollover reaction has taken place.
The 1 H NMR spectrum allows an easy characterization of the products. In particular, the signal of the coordinated DMSO, coupled to 195 Pt, indicates a trans N-Pt-DMSO disposition, as suggested by the high value of 3 J(Pt-H), 23.6 and 23.3 Hz for 4a and 4b, respectively, to be compared to 18.2 and 18.1 Hz in 1a and 1b.
In this case, the reaction likely involves a Cl-assisted mechanism, which may proceed through an oxidative addition/reductive elimination pathway. In an oxidative-addition ionic mechanism, halide ion attack and protonation occur separately. In the two possible pathways either protonation of the metal or coordination of chloride may be the first step [80].
Complexes 4a-b were tested with [H3O⋅18-crown-6][BF4] in the same conditions as 1a-b (1 h, r.t. in acetone solution). The outcome of the reaction of the chloride species is, also in this case, different for the two complexes.
Under mild reaction conditions complex 4a reacts only slightly with [H3O⋅18-crown-6] [BF4], showing that the free nitrogen is not available for protonation and the Pt-C (sp 2 ) bond is fairly stable. No signs of N-H protons are visible in the spectra and only a few amounts of a secondary species can be detected by NMR spectroscopy. Analysis of the signals indicate that the trace species is not a protonated complex, but we were not able to characterize the secondary compound.
In contrast, the chloride derivative 4b, in line with the behavior of the corresponding methyl complex 1b, is easily protonated at the uncoordinated nitrogen, to give also in this case the mesoionic cationic species [Pt(bpy 6Et *)(Cl)(DMSO)] + , 5b, (isolated in the solid state as its BF4 salt).
Also in this case, the 1  In addition to these data, the 1 H NMR spectra of 6a and 6b show a doublet with satellite for the coordinated methyl protons, due to coupling with 31 P and 195 Pt nuclei (e.g., 6a: δ 0.73 ppm, 2 JPt-H = 82.8 Hz, 3 JP-H = 7.8 Hz). Furthermore, the H6′ in 6a-b and the H4 in 7a-b appear strongly shielded, due to the anisotropic effect of the adjacent phenyl rings of PPh3.
The phosphine complexes 6a-b and 7a-b were reacted with acids in order to analyze the influence of PPh3 on the reactivity. Due to the better donor properties of PPh3 compared to DMSO, compounds 6 and 7 are expected to have a higher electron density on the Pt center than the corresponding species 1 and 4.
First, the reaction with [H3O-18-crown-6][BF4] was studied. In contrast to complex 1a, 6a reacts in a clean way with the acid to give the cationic adduct [Pt(bpy 6OMe )(Me)(PPh3)] + . This reaction consists in a "retro-rollover" process, where the C3-Pt bond is attacked by the acid and, after rotation of the internal bipyridine C-C bond, a κ 2 -N,N complex is formed.
It is worth noting that the analogous DMSO complex 1a reacts on the other Pt-C bond, the Pt-CH3 one, releasing methane. In the more electron-rich complex 6a, at variance, the Pt-C(sp 2 ) bond is attached. No evidence of nitrogen protonation was achieved also in this case. The reaction proceeds very fast; as previously reported by some of us, the retro-rollover reaction of similar complexes is faster with better electron-donors (PCy3 > PPh3 > P(OPh)3) [76]. In this case, the combined donor properties of PPh3 and bpy 6OMe may be responsible for the reaction outcome.
The retro-rollover process should lead in principle to two geometric isomers, one with the OMe substituent in cis position to the Me and the other one in trans. Only one isomer, however, is formed during the reaction and can be isolated in the solid state. An extended 1D and 2D NMR investigation, by means of 1 H, 31 P, 1 H COSY and 1 H NOESY spectra, indicate that the isolated species correspond to the less sterically favored isomer, i.e., that with the bulky PPh3 in cis to the methoxy substituent. The 31 P NMR shows a singlet with satellites in line with a P-trans-N arrangement (δ = 17.40 ppm, 1 JPt-P = 4510 Hz). The 1 H NMR shows all the expected aromatic protons and the 1 H NOESY shows correlations between OCH3 and Horto of PPh3 (signals at 2.61 and 7.76 ppm) as well as with H5 (6.79 ppm). Furthermore, the coordinated methyl at 0.64 ppm shows contacts with the Hortho PPh3 protons and H6′ (7.76 and 8.86 ppm, respectively, Figure 7). An analogous retro-rollover process was observed for rollover complexes derived from 2-(2′pyridyl)quinoline (pyqui). In that case, however, two geometric isomers of the cationic adduct [Pt(pyqui)(Me)(PPh3)] + were observed in solution and isolated in the solid state as BF4 salts [76].
The isolation of only one isomer in the case of bpy 6OMe may be attributed to a different reaction pathway or to a higher stability of the observed isomer due to electronic factors. It may be assumed that the methoxy substituent influences the adjacent nitrogen reducing its donor properties and, as a consequence, the ligand with the highest trans-influence, i.e., the methyl, places itself in trans to the donor with the worst trans-influence, i.e., the nitrogen of the substituted pyridine ring, to give the most stable isomer. In agreement, the 3 JPt-H coupling constant of the coordinated methyl protons (74 Hz) is larger than that found in the analogous 2,2′-bipyridine complexed (69 Hz), suggesting a stronger Pt-CH3 bond.
In order to shed more light on the observed outcome of the reaction we performed a series of DFT calculations. The two potential isomers, i.e., PPh3 cis (8a) or trans (8a-iso) to the substituted pyridine ring, were optimized and in agreement with the experimental data we note that 8a is more stable than its corresponding isomer by 10.6 KJ/mol considering only the optimization energy. Following the frequency analysis, we evaluated the ZPE corrected ΔH and ΔG, these values confirm that 8a is more stable by 10.86 and 10.06 KJ/mol, respectively.
A closer look at the optimized geometries verified that 8a is less sterically strained even if the PPh3 is in cis position to the OMe substituent of the bpy, which could seem counterintuitive in terms of the "classical" Tolman cone angle. The phenyl rings of the PPh3 can rotate to accommodate the OMe substituent between them, thus leading to an overall decrease in geometrical strain.
The sum of the internal angles of the metallacycle in 8a is 538.02°, closer to the theoretical 540° for a regular pentagon than 8a-iso, which shows, for the same parameter, 534.46°. The angle between the best planes calculated through the metallacycle (Pt-N1-C2-C2′-N1′) and the one through the coordination plane (Pt-P-C-N1-N1′) is very similar for both isomers but lower for 8a, 12.04 vs. 12.80. It is interesting to observe that the two pyridine rings are bent 12 degrees from the metallacycle plane in 8a-iso while only 7.6° in 8a.
DFT data suggest that the lower stability of 8a-iso is due to a mixture of steric and electronic factors: the less flexible methyl group cis to the OMe substituent of the bpy 6OMe creates a greater distortion in the structure and, being the group with the highest trans-influence in the coordination sphere, is positioned trans to the pyridinic nitrogen which has a stronger trans-influence compared to the one of the substituted ring.
In the case of 8a, the PPh3 accommodates the OMe substituent better and the methyl group places itself in trans to the group that has the lowest trans-influence, in agreement with the trans-influence rule in square planar Pt(II) complexes.
Furthermore, it should also be noted that complex 8a needs an isomerization to be formed, having the unsubstituted pyridine ring in cis to the coordinated methyl group, whereas the starting complex 6a has a cis PPh3-unsubstituted pyridine configuration.
As a conclusion, PPh3 is usually considered a bulky ligand, having a 145° cone angle, on the basis of this value isomer 8a-iso is expected to be the stable isomer. However, as shown by the optimized geometry of 8a, reported in Figure 8, the cone angle should not be considered as a "solid cone" but in some cases can make room inside to host a substituent. This result is interesting and can lead to a revisitation of ligand "bulkiness" and "cone angle" concepts. When the reaction is performed on the second complex, 6b, [Pt(bpy 6Et -H)(Me)(PPh3)], the results are, also in this case, different. In this case the nitrogen is easily protonated to give the mesoionic cationic complex [Pt(bpy 6Et *)(Me)(PPh3)][BF4], 9b-BF4, with high yields. Also in this case, the NMR spectra confirm the proposed formulation; in particular, the NH proton appears as a broad singlet at 13.2 and the 31 P NMR spectrum is in agreement with a P-Pt-C trans coordination (δ = 31.2 ppm; JPt-P = 2400 Hz). Comparison with the parent complex 6b (δ = 32,7 ppm, JPt-P = 2221 Hz) show an increase in the Pt-P coupling constant, indicative of a stronger Pt-P bond. The diagnostic H4 and H3′ protons, as expected, are strongly deshielded with respect to the parent complex 6b: H4 δ = 0.79 ppm, H3′, δ = 0.39 ppm).
Interestingly, complex 9b is fairly stable in solution not giving signs of retro-rollover conversion, whereas the analogous complex [Pt(pyqui*)(Me)(PPh3)] + in 2 days completely converts in its κ 2 -N,N isomer.
The reaction with the adduct H3O + -crown ether was finally studied also in the case of complexes 7a and 7b, [Pt(bpy 6OMe -H)(Cl)(PPh3)] and [Pt(bpy 6Et -H)(Cl)(PPh3)]. Even in this case, the behavior of the two complexes is different; complex 7a does not react with the acid, likely due to the scarce basicity of the free nitrogen atom and the platinum atom. The Pt-C(sp 2 ) bond is stable under the reaction conditions studied and complex 7a is recovered unreacted. In contrast, the free nitrogen in complex 7b is rapidly protonated to give the cationic complex [Pt(bpy 6Et *)(Cl)(PPh3)] + , 10b ( 1 H NMR: δ 13.3 ppm, broad). As expected, after protonation the H4 and H3′ signals appear deshielded by ca 0.8 and 0.5 ppm, respectively. In addition, the 31 P NMR signal moves from 22.61 to 19.59 ppm, with a reduction of the 195 Pt-31 P coupling constant value (from 4297 to 4139 Hz). The complex is stable both in solution and in the solid state.
Proton affinity values (P.A.) were calculated as the reverse enthalpy changes of the reaction reported in Scheme 2, according to ref [81].
It is worth noting that free 2,2′-bipyridines adopt the more stable N,N transoid coplanar conformation [82] (Chart 1, B) found in rollover cyclometalated complexes, in place of the less stable cisoid coplanar configuration (Chart 1, A), adopted in chelated complexes.
In order to compare similar conformations in free ligands and rollover complexes, we comment here only P.A. data for the transoid neutral and protonated species (Chart 1 B → C; Table 4, first line of data). In the protonated ligands, however, the cisoid configuration (D or E) is the most stable one, due to the presence of a weak N-H---N interaction (N---H distances 1.96-1.98 Å). Table 4 (second line of data) also reports true P.A. data, i.e., those relative to the stable species D (bpy 6Et ) or E (bpy 6OMe ). P.A. data limited to transoid conformations (Chart 1, B ➝ C) reported in Table 4, show that bpy 6Et complexes have systematically higher values (ca 34-35 KJ/mol) than corresponding bpy 6OMe ones. Unsubstituted bipyridine complexes (1e-10e) lie in the middle. In contrast, when the free ligands are considered, 2,2′-bipyridine has a lower P.A. value (948.5 KJ/mol) than free bpy 6OMe (952.4 KJ/mol), even considering the cisoid conformations (982.7 vs. 985.0 KJ/mol). Taking into account only transoid conformations, in the ligands the higher P.A. value is shown, as expected, by uncoordinated bpy 6Et (968.3 KJ/mol), only 16 KJ/mol above bpy 6OMe and less than half of the difference found in corresponding complexes. On the whole, all complexes have higher P.A. values than free ligands, with only complex 5a, close to the free ligand.
In contrast, the cisoid conformations of protonated free ligands (D, E) show a remarkable additional stability likely due to the above-mentioned N---H-N interaction. It is worth noting that protonation of free bpy 6OMe affords isomer E as the most stable species, resulting in protonation of the nitrogen of the unsubstituted pyridine ring. It results, on the whole, that the methoxy substituent seems to have a subtle effect on the donor properties of the adjacent nitrogen atom, which effects the overall behavior of bpy 6OMe both as a free ligand and in its complexes.
Extrapolation of these data suggests that while free bpy 6OMe is more basic than bpy, its rollover complexes are less basic; as a consequence, experimentally, its rollover complexes do not show signs of nitrogen protonation.

Conclusions
The behavior of cyclometalated rollover complexes reflects a delicate balance of different contribution from the metal, the ancillary ligands, and the rollover cyclometalated bipyridine. In particular, the nature of the substituent in 6-substituted-2,2′-bipyridines affects not only their behavior towards C(3)-H bond activation, but also the reactivity of the resulting rollover complexes.
All these considerations are also valid for classic cyclometalated complexes; in addition, "rollover" deprotonated ligands have the peculiarity of being no more a spectator in the reactivity of the complex but may act as a "ligand with multiple personalities" due to the presence of the uncoordinated nitrogen.
In particular, the new complexes react in very different ways towards protonation: in addition to differences given by substituents and ancillary ligands, the reaction is complicated by the presence of several nucleophilic centers in the complexes.
Experiments showed that all the bpy 6Et rollover complexes can be easily protonated by [H3O⋅18crown-6][BF4], whereas no evidence of nitrogen-protonation was found for bpy 6OMe complexes, with the possible exception of complex 6a.
Indeed, reaction of complex [Pt(bpy 6OMe -H)(Me)(PPh3)] with [H3O⋅18-crown-6][BF4] results in a retro-rollover reaction whose final product is the cationic adduct [Pt(bpy OMe )(Me)(PPh3)] + . Surprisingly, only the isomer with the cis-PPh3-OMe geometry is formed, in spite of an expected instability due to steric hindrance of the PPh3 ligand (cone angle 145°). Surprisingly, the OMe substituent is situated in the neighborhood of the phenyl rings of the bulky PPh3 rather than close to the much smaller methyl ligand. This result reminds us that too often the cone angle is considered as a real "solid cone", which is not always true. This result is interesting and may elicit a reflection on the use and interpretation of the cone angle concept.