Non-classical effects in proton or hydrogen transfer

Introduction

The transfer of a proton or hydrogen, often referred to as “the simplest chemical reaction”, is, in fact, a very complicated process. The reason is the quantum nature of proton and its propensity to tunnel. Since tunneling is extremely sensitive to the potential energy barrier “seen” by the proton, and this barrier changes as the atoms vibrate, accurate description of tautomerization is a formidable task. Our work on systems engaged in intra- or intermolecular hydrogen bonds focuses on the understanding of tautomerization mechanisms, which is mandatory for the precise description of the reaction path. I will present several examples of “unusual” proton transfers, which should no longer be called unusual once the mechanisms responsible for tautomerization are elucidated. The second part will focus on the outstanding features of tautomerism in porphycenes. Finally, studies of tautomerization in single molecules will be presented.

Example 1. Mode-selective excited state proton transfer in 2-(2′-pyridyl)pyrrole. This molecule exhibits excited state intramolecular proton transfer (ESIPT), manifested by the appearance of dual fluorescence: F₁, corresponding to the initially excited species, and F₂, originating from the tautomer formed in S₁ after proton translocation from the pyrrole to pyridyl nitrogen (Fig. 1). Dual emission is observed not only in solutions [1], but also for molecules isolated in supersonic jets [2], where the reaction becomes vibrational-mode specific: Tautomerization occurs after selective excitation into the vibronic levels corresponding to two in-plane modes, those that lead to the decrease of the N···N distance (and thus, to the increase of hydrogen bond strength). Excitation of other modes does not lead to the reaction, even though the energy deposited in the molecule may be larger than in the previous case. This finding immediately shows the danger involved in using 1D reaction models, which predict that when more energy is put into the system, it gets closer to the barrier, and the reaction is accelerated. In reality, vibrational excitation does not always help. Depending on the form of a particular vibrational mode, tautomerization may be enhanced, slowed down, or not influenced by vibrational excitation.

Fig. 1:

Vibrational mode-specific excited state intramolecular proton transfer in 2-(2′-pyridyl)pyrrole isolated in supersonic jet. Depending on which vibration is excited the molecule can either (a) remain in the initially excited form and emit “normal” fluorescence (F₁) or (b) tunnel to the tautomeric form, identified by the red-shifted fluorescence (F₂).

Kinetic isotope effect of 30–60, proving the tunneling mechanism, were obtained from the comparison of F₁/F₂ intensity ratios in non-deuterated and N-deuterated 2-(2′-pyridyl)pyrrole [2].

Example 2. Coupling between excited state proton transfer and a large-amplitude twisting motion. Photoexcited syn rotamer of 7-(2′-pyridyl)indole decays very rapidly: The S₁ lifetime in solution at 293 K is ca 1 ps. Remarkably, in the supersonic jet regime the decay becomes faster than in room temperature solution (280 fs and 390 fs in N-deuterated molecule). This was interpreted [3] as evidence of coupling of proton transfer with twisting of the pyridyl group with respect to the indole moiety (Fig. 2). Theory predicts the proton transfer to be barrierless and coupled to the indole-pyridine torsional coordinate [4]. The apparently unusual increase of the reaction rate at lower temperatures has been explained by the presence of viscosity barrier in solution and its absence in jet-isolated molecules.

Fig. 2:

Excited state intramolecular proton transfer in 7-(2′-pyridyl)indole is accompanied by twisting. Proper description of the reaction path requires using at least two coordinates, denoted here as r_NH and φ.

Example 3. Double hydrogen transfer is faster than a single hydrogen transfer reaction. Coupling of tautomerization with torsional motions of methyl groups. Meso-tetramethyl-substituted porphycene (Fig. 3) exhibits ultrafast (<100 fs) trans-trans double hydrogen transfer, whereas the translocation of a single hydrogen atom trans-cis-trans is much slower [5]. This has been explained by coupling of single hydrogen transfer with the torsional motion of methyl substituents, and the lack of such coupling in the case of the double hydrogen transfer process. In other words, the reaction coordinates are very different for single and double hydrogen transfer processes.

Fig. 3:

Trans-trans interconversion in 9,10,19,20-tetramethylporphycene is ultrafast, but the cis-trans and trans-cis processes are much slower.

Example 4. Tautomerization rate in a single molecule becomes temporarily slower by many orders of magnitude. Trans-trans conversion has been studied for 2,7,12,17-tetraphenylporphycene on a single molecule level using fluorescence microscopy [6]. The analysis of the spatial fluorescence patterns of more than 850 single molecules, revealed, for a small fraction (about 5%), an unusual behavior: change ot tautomerization rate with time. The average tautomerization time, determined from measurements on bulk samples, is about 1 ps. In contrast, in some of the single molecules, this time was extended to minutes. The huge decrease of the tautomerization rate was explained by the inability of the molecule to assume a conformation corresponding to a symmetric double minimum potential (Fig. 4). Such behavior may be due to the low frequency torsional motions of phenyl substituents, coupled to the motions of the polymer matrix.

Fig. 4:

Bottom, confocal fluorescence microscopy images of fluorescence of single molecules of 2,7,12,17-tetraphenylporphycene embedded in a polymer film at 293 K. Images (a) and (b) correspond to two consecutive 20 min scans. The molecule indicated by the circle switches from a “locked” state (a) to a regime of fast tautomerization (b). Top, schematic representation of the potential energy profiles for the two cases.

Outstanding features of tautomerism in porphycenes

Due to strong intramolecular hydrogen bonds and well defined geometry of the inner cavity, porphycenes are well-suited for studies of non-classical effects in tautomerization. They are also interesting for investigations in other areas, such as photodynamic therapy, photostability, or possible application as dyes.

Electronic spectra recorded for cold porphycene, isolated in supersonic jets or helium nanodroplets reveal tunneling splittings [7]. The magnitude of the splittings is much larger in S₀ than in S₁: 4.4 vs<0.2 cm⁻¹, respectively, for the 0–0 transition. Single vibronic level fluorescence spectra (Fig. 5) show that the tunneling splittings are vibrational mode-specific [8], [9]. In other words, the barrier to tautomerization may change with vibrational excitation. Both an increase (12 cm⁻¹ for the 2A_g mode) and decrease (to a value <1 cm⁻¹ for 1A_g) have been observed. Most bands reveal splittings similar to that observed for the vibrationless level. However, a “neutral” mode may change its character when the molecule is isotopically substituted, even at positions remote from the inner cavity. Such a case was observed for the 4A_g mode: in the nondeuterated porphycene it exhibits practically the same splitting as the zero point level, but in the molecule with all 12 peripheral protons replaced by deuterons, this value increases to 9 cm⁻¹ [10]. Such a “reversed isotope effect” clearly demonstrates the multidimensional character of the potential responsible for hydrogen transfer. It is possible to reproduce the increased/decreased splittings by using the models of 2D symmetric or antisymmetric coupling between the high frequency NH stretching vibration and a low frequency mode [11]. In order to simulate the case when both tautomerization enhancing and hindering modes are simultaneously excited, symmetric and antisymmetric mode coupling can be combined. These results demonstrate that the correct potential should be multidimensional.

Fig. 5:

Single vibronic level fluorescence spectra of porphycene isolated in a supersonic jet. Spectra (a), (b), and (d) correspond to the emission obtained by exciting the 2A_g vibrational mode in the S₁ state (v′=1, 2, and 3, respectively), whereas the spectrum (c) was obtained for 4A_g excitation. Ground state vibrational levels are denoted by v″.

In a condensed phase (solutions, glasses, polymers), the two inner protons are no longer coherently delocalized. Tautomerization now becomes a rate process. Since the trans-trans conversion is a self-exchange process, i.e. the substrate and product are chemically equivalent, special techniques are required for rate determination. They are based on pump-probe spectroscopy with polarized light [12], and the reaction rate can be determined from the analysis of transient absorption anisotropy (r(t)) signals:

ΔA(t)_par and ΔA(t)_perp denote changes in absorbance measured for probe polarization parallel and perpendicular to the polarization of pump pulse, respectively. Examples of transient anisotropy curves are provided in Fig. 6. The measured signal may contain contributions from (a) ground state depopulation by the pump pulse (bleaching); (b) stimulated emission; (c) transient absorption originating from the excited state. A proper choice of pump and probe wavelengths enables the separation of these contributions and the simultaneous determination of ground ( k P T 0 ) and excited state ( k P T 1 ) tautomerization rates from transient absorption anisotropy values:

Fig. 6:

Kinetic profiles of the anisotropy r(t) measured, after excitation to the S₁ state, for four different porphycenes in paraffin oil solution at room temperature.

where f is the relative contribution from S₀, r 0 0 and r 0 1 are the anisotropy values at the moment of excitation, and r ∞ 0 and r ∞ 1 denote asymptotic values due to S₀ and S₁ at an infinitely long delay.

This procedure has now been applied for more than 20 differently substituted porphycenes [13], [14], [15]. The rates span more than three orders of magnitude and correlate well with the parameters that characterize the strength of intramolecular hydrogen bonds: the NH stretching frequencies, N-N distances, proton chemical shifts. The large rate variations are indicative of tunneling. In order to determine its role in tautomerization, parent porphycene and 2,7,12,17-tetra-tert-butyl porphycene, together with their –d2 isotopologues (inner protons substituted with deuterons) have been studied in a wide temperature range, 20–500 K [16]. It was found that the rate can be described assuming contributions from three different channels, of which two correspond to (i) tunneling from a vibrational ground state; (ii) vibrationally-activated tunneling (via the 2A_g mode). Even at room temperature, the role of these two channels is dominant, showing that tunneling may be the major reaction path even under “normal” conditions.

It is interesting to check if the data obtained for the two regimes – isolated molecules and condensed phases – are compatible. For incoherent tunneling, the rate is proportional to Δ². Using the experimental data obtained for porphycene in the vibrationless state and for the v=1 level of the 2Ag mode, one obtains: (12/4.4)²=7.4. This is in perfect agreement with the corresponding ratio of the rates determined for the two tunneling channels: k₁/k₀=7.0±0.9.

Tautomerism in single molecules

It has now become possible to observe tautomerism in single molecules. For porphycene, this has been achieved using three different techniques. The first was fluorescence microscopy [17], [18] (Fig. 7). Spatial images of emission from single chromophores are recorded while using polarized light for excitation (the so-called radial and azimuthal polarization modes). Certain image shapes, such as a ring pattern, observed for molecule Σ in Fig. 7, cannot be obtained when the emission is due to a single oscillating dipole, but they can be simulated assuming two transition moments forming a certain angle (ca. 72° for porphycene). This corresponds to two trans tautomers rapidly interconverting on the time scale of the experiment (usually seconds). Investigation of single molecules enables observing events that are not detected while studying ensembles, and thus averaging over large number of molecules. Example 4, presented above (Fig. 4), describes such a situation: a small fraction of single molecules of 2,7,12,17-tetraphenylporphycene was found to exhibit an unusual behavior: switching between the regime of slow and fast tautomerization over a period of minutes.

Fig. 7:

(a) Confocal image of two porphycene molecules showing two typical fluorescence patterns: a ring pattern for molecule Σ and a double-lobe pattern for molecule Π. (b) 3D plot of the same area as in (a). (c), (d) Simulated fluorescence patterns, assuming two differently oriented molecules with two transition dipole moments forming an angle of 72°. Scan area: 2.5×2.5 μm²). Reprinted with permission from Ref. [17]. Copyright (2005) American Chemical Society.

Not only fluorescence, but also Raman spectra of single molecules can now be obtained. Surface-enhanced resonance Raman spectra were recorded for single porphycene molecules located on gold nanostructures [19], [20]. Thousands of spectra could be registered from the same molecule at a rate of several spectra per second. Analysis of the consecutive spectra revealed infrequent, reversible changes: disappearance of some bands and the appearance of new ones. Such behavior was interpreted as due to trans-cis-trans tautomerization in single porphycene molecules. This conclusion was supported by calculations of vibrational structure.

Unlike optical methods that monitor the reaction via fluorescence or Raman spectra, scanning probe microscopies enable looking “directly” at protons in single, tautomerizing molecules (Fig. 8). Scanning tunneling microscopy experiments were performed for porphycene located on Cu(110) surface, under high vacuum at 5 K [21], [22], [23], [24], [25]. Under such conditions, the molecule was found to exist in the cis form, a structure not observed previously for parent porphycene. Cis-cis reaction rates could be determined from the analysis of time intervals observed between tautomerization events. Tautomerization could be induced by heating, but also by inelastic electron scattering, leading to vibrational excitation of porphycene. The reaction activated in this way was found to be vibrational mode-specific [22]. Further STM/AFM experiments demonstrated that tautomerization in single porphycene molecules on copper surface can also be induced by two other stimuli: (a) light [24]; (b) mechanical force [25]. An impressive result was the possibility to switch between two cis tautomers by moving a single copper atom in the vicinity of a single porphycene molecule [21].

Fig. 8:

Top, STM images of a single porphycene molecule on a Cu(110) surface at 5 K, demonstrating the existence of two cis tautomeric forms. Bottom, current traces obtained for a fixed tip position, illustrating switching between the two tautomers. Adapted from Ref. [21].

Conclusions

The experiments described above leave no doubt that the proper explanation of proton/hydrogen transfer reactions cannot neglect tunneling and the contributions from different vibrational modes to the reaction path. Thus, accurate description of tautomerism requires a multidimensional approach with explicit consideration of tunneling.

Studies of meso-substituted porphycenes reveal that proton transfer can be coupled to conformational changes, such as methyl group rotation. Another example is provided by photoinduced proton transfer in 7-(2′-pyridyl)indole.

Tunneling splittings due to coherent delocalization of two internal protons in porphycene are vibrational mode-specific. In other words, the barrier to hydrogen transfer may strongly depend on the vibrational state of the molecule. This was also demonstrated for the electronically excited 2-(2′-pyridyl)pyrrole.

A general conclusion that emerges from extensive studies of porphycenes, carried out under diverse experimental regimes, such as condensed phases, isolated or single molecules is that the quantum effects, tunneling in particular, are important, and perhaps even dominant, even for “normal”, routinely used molecular environments: room temperature solutions. Non-classical effects in proton/hydrogen transfer should be always taken into account while trying to understand the intricacies of tautomerism.