8.22 Financial execution of the project, diffusion of the results, and students training has been carried according to the plan. Annual reports on project execution have been prepared and presented. A project website with the information of all achievements has been published, and the resulted scientific publications deposited for open access. Grounded on the breakthroughs of the project, the prospect for future investigations oriented to quest fundamental scientific question or practical applications have been considered.

We successfully achieved milestone 8: Project Conclusion.

However, this is not really the end as further investigations and the training of MSc/PhD students and Postdoc continues, thanks to the aCTIVE project!

7.22 The aCTIVE project is reaching its final days, and we have been reviewing the achievements. A book chapter in the Wiley-VCH (link or repository) and a review article in the Chem. Soc. Rev. (link or repository) have just been published, highlighting our discoveries on quantum tunneling and infrared vibrational excitation chemistry that were achieved during the execution of the project. Thanks to all the team involved in this research journey!

7.22 During the project execution, we have investigated around 32 target molecules or precursors of target reactive intermediates, 11 of which were synthesized. That number was considerable larger than that initially planned!

We achieved milestone 2: The required target molecules and precursors of target reactive intermediate are synthesized.

7.22 In our final work on task 5 (see also entries 6.22 and 7.21), as planned, we investigated vibrational excitation chemistry of benzazirines targets having potential competitive reactions. We successfully generated the isomeric 2-fluoro-4-hydroxy-2H-benzazirine (2FB) and 6-fluoro-4-hydroxy-2H-benzazirine (6FB) in krypton matrixes (using 2-fluoro-4-hydroxyphenylazide as precursor). Then, we remarkably found that near-IR-light irradiation at the first OH stretching overtone frequencies (remote vibrational antenna) of the benzazirines induces the 2FB ring‑expansion reaction to cyclic ketenimine whereas the 6FB ring-opening reaction to triplet nitrene. Computations demonstrate that these isomeric benzazirines have distinct reaction energy profiles, which allow to conclude that the vibrational excitation selectively activates only of the most favorable bond‑breaking/bond-forming pathway available. These pioneer results on differential vibrationally-induced (and tunneling-driven) reactivity in two isomeric benzazirines have just published in Chem. Eur. J. (link-OA).

We achieved milestone 5: Fundamental knowledge was acquired to elucidate advantages, opportunities and limitations of chemistry triggered by infrared vibrational excitation.

7.22 We extent the studies carried out with 2‑formylphenylnitrenes (entry 6.20) now using a nitrogen matrix medium. Although again their target 2v(CH) weak bands were not identified, we discovered that syn and anti (-CHO) conformers of 2‑formyl-3-fluorophenylnitrene react simultaneously and independently by pure quantum tunneling to distinct rearrangement products. Although the energy barrier between the nitrene conformers is significantly lower than any of the observed reactions, no conformational interconversion was observed. This consists of an unprecedented exemplar of conformer‑specific tunneling reactions operating simultaneously by the paradigm of tunneling control, yielding a product outcome that cannot be rationalized by the conventional kinetic or thermodynamic control. The results have just been accepted for publication in J. Am. Chem. Soc. (link or repository).

6.22 We extended task 5 to investigate the thymol molecule, which in comparison to carvacrol, has the competitive rotamerizations of isopropyl (higher energy) and hydroxyl (lower energy) with an opposite barrier height trend. We noticed that in contrast with the rotamerization of the isopropyl group observed in carvacrol, no rotamerization were observed in thymol upon vibrational excitation at its 2νOH frequency. These results indicate that the vibrational energy is more efficiently transferred and selective activates the lower energy reaction coordinate available, which for thymol is the OH-rotamerization (fast relaxation tunneling precludes its observation) and for carvacrol is the C3H7-rotamerization. The study on the conformational structure, infrared spectra, and light-induced transformations of thymol isolated in noble gas cryomatrices has just been published in Photochem (link-OA).

Investigations were latter also extended to 2,3-dihydroxybenzaldehyde and 2,4-dihydroxybenzaldehyde molecules, which are targets possessing two vibrational antennas and two possible reaction coordinates. Preliminary results obtained with these molecules have just been accepted for publication in J. Phys. Chem. A. (link or repository).

4.22 As planned in the task 7, we performed investigations on the activation of molecular switches and of Bergman cyclization reactions. The most successful results were obtained with 6-hydroxyspiropyran under matrix isolation conditions, where we discovered an unprecedented bidirectional photoswitching between a colored merocyanine and a colorless allene intermediate species. Although it has been generally assumed that open merocyanines photochemically revert to the closed-ring spiropyrans, our work disproves such view. These results have just been published in J. Phys. Chem. A. (link or repository).

A remarkable progress was made to achieve the milestone 7 (see also entry 10.19) - the excitation of second stretching overtones of vibrational antennas is applied to mirror the activation of drugs and the switching of materials - but to attain such groundbreaking achievements further investigations are still needed.

2.22 Gil. M. Ferreira have just defended his MSc thesis. He has been working on the aCTIVE project investigating the generation and characterization of nitrilimines in cryogenic matrices and their reactivity by electronic and vibrational excitation.

1.22 We have just closed a position for two MSc Researchers. Mariana Peixoto and Bruna Costa were selected and will be working on the aCTIVE project in the next 6 months.

10.21 A promotional video about the research work of the aCTIVE project was released. We had the collaboration of the communication division of the University of Coimbra. Thanks also to the Faculty of Sciences and Technology team for advertising the aCTIVE project throughout different channels:

https://www.uc.pt/fctuc/investigacao-em-destaque/quimica-induzida-por-excitacao-vibracional-no-infravermelho

https://www.facebook.com/fctuc

https://youtu.be/QWndOTP-3V4

https://www.instagram.com/p/CUr3A7CjPmH/

https://twitter.com/FCTUC

8.21 Our work on molecular reactions by selective vibrational excitation of a remote antenna with near-infrared light has just been published in Chem. Comm. (link or repository).

In task 4, we envisioned a generalized strategy for inducing bond-breaking/bond-forming reactions using a vibrational antenna remotely attached from the reaction center of the target molecule. These antennas act as an ideal gateway to selective introduce a precise amount of energy in a molecule using narrowband near-IR irradiation. As a proof-of-principle of such strategy, we demonstrated that selective vibrational excitation of a OH remote antenna in a benzazirine successfully triggers its electrocyclic ring-expansion to a cyclic ketenimine, under cryogenic conditions. This accomplishment paves the way for harnessing IR vibrational excitation as a tool to guide a variety of molecular structure manipulations in unprecedented highly-selective fashion.

We achieved project milestone 4: Chemistry triggered by infrared vibrational excitation was expanded by using vibrational antennas remotely located in relation to reaction coordinates.

7.21 We explored the effect of using non-inert low-temperature conditions, namely thin films of amorphous and crystalline target molecules (link or repository). Thiotropolone was study isolated in noble-gas matrices (also entry 9.20) and in a neat solid (crystalline or amorphous states) at low temperatures. Apart from the thermal and electronic excitation tautomerizations, we found that narrowband IR irradiation of the SH form in neat solid induces tautomerization to the OH form. As far as we are aware, such results constitute a pioneer demonstration of chemistry induced by vibrational excitation under neat solid conditions, which opens the door for envision practical applications. There results have just been published in J. Phys. Chem. A (link or repository).

5.21 Our work demonstrating how to switch on H-tunneling upon conformational control by vibrational excitation has just been published in J. Am. Chem. Soc. (link or repository).

As planned in task 3, we investigated the possibility of activating tunneling reaction using vibrational excitation. Such goal was achieved with a triplet 2-hydroxyphenylnitrene generated in an N₂ matrix at 10 K by UV-irradiation of an azide precursor. The anti-orientation of the nitrene’s OH moiety was converted to syn-orientation by selective vibrational excitation at the 2ν(OH) frequency, thereby moving the H atom closer to the vicinal nitrene center. This triggers the spontaneous H-tunneling to a singlet 6-imino-2,4-cyclohexadienone. Overall, our work provides a conceptual strategy to harness the control of QMT, which is likely to inspire new advances that can extend from enzymatic catalysis to quantum switches. Project milestone 3 was fully achieved (see also entry 9.20).

2.21 We have applied the weak-coupling (WC) formulation of non-adiabatic transition state theory (NA-TST) to pioneer uncover the existence of spin-forbidden tunneling reactions during our studies with target nitrenes and benzazirines (tasks 3 and 4; see entries 5.21 and 6.20). Now, in an exclusive theoretical work with Luís P. Viegas, we show how the WC formulation of the NA-TST can satisfactorily predict the occurrence of a spin‑forbidden tunneling reaction under low temperature regime. This was apply to undercover that the Closs’s diradical triplet cyclopentane-1,3-diyl undergoes ring closure to singlet bicyclo[2.1.0]pentane in a cryogenic glasses by heavy-atom tunneling through crossing the triplet-to-singlet potential energy surfaces. These results have just been published in Phys. Chem. Chem. Phys. [2021 PCCP HOT Articles (link-OA)].

2.21 We extended task 3 to investigate the transformation of a ketenimine to 2-cyanophenol by vibrational excitation. Ketenimine was successfully prepared by UV-irradiation of 1,2-benzisoxazole but due to the small amount generated its 2v(NH) was not detected. Alternatively, the photochemistry of 2-cyanophenol and 1,3-benzoxazole was explored but the amount of ketenimine trapped was even smaller, which precluded the investigation of vibrational excitation chemistry. Nevertheless, these UV-irradiation results were published in J. Org. Chem. (link or repository). The 2-isocyanophenol generated was irradiated at its 2v(OH) frequency and conformational interconversion was achieved. Vibrational excitation with full or filtered broadband light of the IR spectrometer source also promoted isomerizations - low energy vibrational modes were observed to play a significant role. Moreover, we discovered that a tunneling reaction can affect the conformational composition of 2-isocyanophenol trapped in a nitrogen matrix and be entangled with the effects of the IR radiation. There results were published in Chem. Phys. Lett. (link or repository).

9.20 We have just published a book chapter in the Royal Society of Chemistry, highlighting our work on tunneling reactions with benzazirines and phenylnitrenes, as well as some infrared vibrational excitation chemistry achieved during the execution of this project. See it here or in the repository.

9.20 Our work demonstrating an unprecedented example of a bond-breaking/bond-forming reaction by vibrational excitation under matrix isolation conditions has just been published in J. Phys. Chem. Lett (link or repository) .

As planned in task 3, we investigated thiotropolone and found that narrowband IR-irradiations tuned at the frequencies of first CH stretching overtone or combination modes of the OH tautomer, the sole form of the compound existing in the as-deposited matrices, led to its conversion into the SH tautomer. The tautomerization in the reverse direction was achieved by vibrational excitation of the SH tautomer with irradiations corresponding to the frequencies of its CH stretching overtone or combination modes. The current pioneer demonstration of bidirectional hydroxyl - thiol tautomerization controlled by vibrational excitation opens the door to advances in vibrationally induced chemistry.

We achieved project milestone 3: The first results of chemistry (bond-breaking/bond-forming reactions) triggered by infrared vibrational excitation of molecules in cryogenic matrices were attained.

6.20 We explored the manipulation of the aldeyde (-CHO) orientation in 2-formylphenylnitrenes and the control of proton tunneling upon vibrational excitation. However, due to the small amount of nitrene generated in cryogenic matrices their target 2v(CH) weak bands were not identified. Nevertheless, we discovered that triplet syn-2-formyl-3-fluorophenylnitrene in argon matrices spontaneously cyclizes to singlet 4-fluoro-2,1-benzisoxazole by heavy-atom tunneling through crossing potential energy surfaces. There results have just been published in Angew. Chem. Int. Ed. (link or repository) [featured as a VIP Very Important Paper].

10.19 While working with thioacetamide (see also entry 6.19), we discovered that an imino NH group can be use as a remote vibrational antenna to manipulate a molecular structure (task 4). Selective and reversible conformation isomerization of thioacetamide thiol forms were achieved by IR-irradiation at their 2v(NH) frequencies. Quantum yields for SH-rotamerization in the imino-thiol isomers, resulting from the vibrational excitation of the remote NH antenna, were found comparable to those for OH-rotamerization in carboxylic and amino acids, resulting from direct vibrational excitation of the OH group. These results have just been published in Phys. Chem. Chem. Phys. [2019 PCCP HOT Articles (link-OA)].

10.19 Our work showing chemistry triggered by vibrational excitation of second stretching overtones has just been published in Phys. Chem. Chem. Phys. [This articles is part of the themed collection: 2019 PCCP HOT Articles (link-OA)].

Here, for the first time, we successfully measured second stretching overtones of molecules isolated in cryogenic conditions and demonstrated the use of vibrational excitation of these modes to trigger conformational isomerizations. These results open the door to extend the control over conformations separated by high barriers and to induce other transformations not energetically accessible by excitation of fundamental or first stretching overtone modes.

We achieved project milestone 1: The new equipment is fully operational and protocols are established for identification and to induce chemistry by vibrational excitation at the second stretching overtones.

8.19 Investigations on the chemistry triggered by excitation of first stretching overtones remotely located in relation to a reaction coordinate were initiated using the ring-expansion of a benzazirine as a target model (task 4). A benzazirine derivative having a para-amino moiety as a vibrational antenna was successfully generated in solid argon at 3–18 K. The extreme reactivity found for this species precluded any vibrational excitation study. However, this led us to discover a new reactivity paradigm, the occurrence of two competitive tunneling reactions originating from the same chemical species. There results have just been published in J. Am. Chem. Soc. (link or repository).

6.19 We have just closed a position for a PhD Junior Researcher. Nelson A. M. Pereira was selected and will be working on the aCTIVE project in the next 3 years.

6.19 As planned in the task 3, the possibility to trigger tunneling reactions by vibrational excitation was investigated using thiourea as a prototype molecule. Irradiation experiments at the imino 2v(N-H) frequency of the high-energy thiol form were carried out but no increase in the rate of tunneling tautomerization to the thione form has been unequivocally detected. The initial plan was extended to investigations on thioacetamide. We then discovered S–H rotamerization tunneling in a thiol form of thioacetamide generated in cryogenic matrices. These results, demonstrating for the first time that tunneling plays a role in the conformational isomerization of sulfur-containing compounds, have just been published in Phys. Chem. Chem. Phys. (link or repository).

5.19 While working with 2-cyanophenol as a prototype molecule for task 1, we discovered that broadband IR radiation emitted by the FTIR spectrometer source can induce conformational isomerizations. This phenomenon was investigated in detail using different long-pass IR filters in front of the FTIR globar source. Moreover, it was discovered that a tunneling reaction can affect the conformational composition of 2-cyanophenol trapped in cryogenic conditions and be entangled with the effects of the IR radiation. These results have just been published in J. Phys. Chem. A. (link or repository).

3.19 A new tunable diode laser with a master oscillator power amplified was installed and is operating successfully. We also developed a new prototype system bases on a optical fiber to carried the light from the diode laser to our matrix cryogenic system. This will allow us to selectively excite second stretching overtone modes of monomeric cryogenic samples with near-IR light in the 10000-10500 cm-1 region (1000-950 nm) with more than 1 W of power.

2.19 A new TE cooled InGaAs detector for near-IR region was installed in our Thermo Nicolet 6700 FTIR spectrometer. Using this detector, we expect to be able to measure second stretching overtone modes (specially in the 11000-9000 cm-1 region) of monomeric molecules isolated in cryogenic matrices.

12.18 The computational chemistry software package GAUSSIAN 16 was installed and it is running in our new 16-core CPU computer.

7.18 Our aCTIVE project start today!