Site-Selective C–H Functionalization on Coumarins Directed by Manganese: Mechanistic Insights from Time-Resolved Spectroscopy and Catalytic Development

The rapid development of light-activated organic photoredox catalysts has led to the proliferation of powerful synthetic chemical strategies with industrial and pharmaceutical applications. Despite the advancement in synthetic approaches, a detailed understanding of the mechanisms governing these reactions has lagged. Time-resolved optical spectroscopy provides a method to track organic photoredox catalysis processes and reveal the energy pathways that drive reaction mechanisms. These measurements are sensitive to key processes in organic photoredox catalysis such as charge or energy transfer, lifetimes of singlet or triplet states, and solvation dynamics. The sensitivity and specificity of ultrafast spectroscopic measurements can provide a new perspective on the mechanisms of these reactions, including electron-transfer events, the role of solvent, and the short lifetimes of radical intermediates.

The electrochemical reduction of CO2 (CO2RR) represents a compelling approach to address the energy crisis by closing the carbon cycle and converting renewable energy into valuable multicarbon fuels and chemicals [1]. Cu2O nanocubes have demonstrated effective catalytic activity in producing various C2+ hydrocarbons, although they exhibit broad product selectivity [2]. To enhance selectivity for energy-rich products like ethanol, strategies such as modifying the catalyst's structure and composition through oxide-derived and bimetallic approaches have been explored [3]. Recently, pulsed CO2RR has been employed as an effective method to adjust product selectivity toward ethanol in situ, eliminating the need for extensive redesigns of the catalytic system [4]. Nonetheless, mechanistic insights are essential and require comprehensive operando studies to identify the dynamic interplay of the electrocatalytic interface.This study aims to deepen our understanding of the catalyst-adsorbate interactions specific to ethanol production by employing sub-second time-resolved operando spectroscopy and diffraction techniques during CO2RR. We synthesized bare and ZnOx-decorated Cu2O nanocubes with 30 nm edge lengths using a simple ligand-free method. During pulsed CO2RR on monometallic Cu cubes, we monitored the evolution of key adsorbates using time-resolved operando surface-enhanced Raman spectroscopy (SERS). Our experiments across various pulse length conditions revealed the pivotal roles of co-adsorbed hydroxide and CO on the Cu surface and the oxidative formation of Cu-Oad or CuOx/(OH)y species, which significantly affect CO adsorption kinetics and enhance ethanol selectivity. Notably, insufficient hydroxide coverage leads to increased C1 product selectivity due to the formation of bulk-like Cu2O, while excessive hydroxide coverage inhibits C-C coupling [5].These findings were further validated by studying a bimetallic Cu-ZnO nanocatalyst under pulsed CO2RR conditions, where the selectivity could be modulated by adjusting the anodic potential while the pulse length remained constant. Time-resolved operando techniques including X-ray absorption spectroscopy (XAS), SERS, and X-ray diffraction (XRD) revealed the dynamic interactions among Cu, Zn, and the CuZn alloy, which formed under CO2RR conditions, as well as the adsorption behaviors of hydroxide and CO. These insights highlight the critical role of oxides and hydroxide coverage in enhancing ethanol selectivity, which can be finely tuned through the oxidative modification of Cu- or Cu-Zn-based catalytic materials using potential pulses. This enhances our fundamental understanding of the mechanisms underlying CO2RR, significantly advancing the field.

Novel time-resolved near-infrared spectroscopy (TR-NIRS), with adipose tissue thickness correction, was used to test the hypotheses that heavy priming exercise reduces the V̇O2 slow component (V̇O2SC) (1) by elevating microvascular [Hb] volume at multiple sites within the quadriceps femoris (2) rather than reducing the heterogeneity of muscle deoxygenation kinetics. Twelve subjects completed two 6-min bouts of heavy work rate exercise, separated by 6 min of unloaded cycling. Priming exercise induced faster overall V̇O2 kinetics consequent to a substantial reduction in the V̇O2SC (0.27 ± 0.12 vs. 0.11 ± 0.09 L·min−1, P < 0.05) with an unchanged primary V̇O2 time constant. An increased baseline for the primed bout [total (Hb + Mb)] (197.5 ± 21.6 vs. 210.7 ± 22.5 μmol L−1, P < 0.01), reflecting increased microvascular [Hb] volume, correlated significantly with the V̇O2SC reduction. At multiple sites within the quadriceps femoris, priming exercise reduced the baseline and slowed the increase in [deoxy (Hb + Mb)]. Changes in the intersite coefficient of variation in the time delay and time constant of [deoxy (Hb + Mb)] during the second bout were not correlated with the V̇O2SC reduction. These results support a mechanistic link between priming exercise-induced increase in muscle [Hb] volume and the reduced V̇O2SC that serves to speed overall V̇O2 kinetics. However, reduction in the heterogeneity of muscle deoxygenation kinetics does not appear to be an obligatory feature of the priming response.

Light works: Mechanistic insights into the photochemical events and charge dynamics of a donor–acceptor covalent organic framework were given by time-resolved transient absorption spectroscopy and time-resolved electron spin resonance spectroscopy (see picture). The organic framework triggers ultrafast electron transfer and enables long-distance charge delocalization and exceptional long-term charge separation.

Highly enhanced photoluminescence and suppressed blinking of N-doped carbon dots by targeted passivation of amine group for mechanistic insights and Vis-NIR excitation bioimaging application

A brief review of hot-carrier dynamics in metal halide perovskites: mechanistic insights from time-resolved spectroscopy

Ultrafast carrier relaxation in SnSe (x=1, 2) thin films observed using femtosecond time-resolved transient absorption spectroscopy

HNO is a highly reactive molecule that shows promise in treating heart failure. Molecules that rapidly release HNO with precise spatial and temporal control are needed to investigate the biology of this signaling molecule. (Hydroxynaphthalen-2-yl)methyl-photocaged N-hydroxysulfonamides are a new class of photoactive HNO generators. Recently, it was shown that a (6-hydroxynaphthalen-2-yl)methyl (6,2-HNM)-photocaged derivative of N-hydroxysulfonamide incorporating the trifluoromethanesulfonamidoxy group (1) quantitatively generates HNO. Mechanistic studies have now been carried out on this system and reveal that the ground state protonation state plays a key role in whether concerted heterolytic C-O/N-S bond cleavage to release HNO occurs versus undesired O-N bond cleavage. N-Deprotonation of 1 can be achieved by adding an aqueous buffer or a carboxylate salt to an aprotic solvent. Evidence is presented for C-O/N-S bond heterolysis occurring directly from the singlet excited state of the N-deprotonated parent molecule on the picosecond time scale, using femtosecond time-resolved transient absorption spectroscopy, to give a carbocation and 1NO-. This is consistent with the observation of significant fluorescence quenching when HNO is generated. The carbocation intermediate reacts rapidly with nucleophiles including water, MeOH, or even (H)NO in the absence of a molecule that reacts rapidly with (H)NO to give an oxime.

Use of fluorescence spectroscopy to study conformational changes in the β2-adrenoceptor

Time-resolved photoelectron imaging was used to study non-adiabatic relaxation dynamics in gas-phase indole following photo-excitation at 267 nm and 258 nm. Our data analysis was supported by various ab initio calculations using both coupled cluster and density functional methods. The highly differential energy- and angle-resolved information provided by our experimental approach provides extremely subtle details of the complex interactions occurring between several low-lying electronically excited states. In particular, new insight into the role and fate of the mixed Rydberg-valence 3s/πσ* state is revealed. This includes population residing on the excited state surface at large N-H separations for a relatively long period of time (∼1 ps) prior to dissociation and/or internal conversion. Our findings may, in part, be rationalized by considering the rapid evolution of this state's electronic character as the N-H stretching coordinate is extended - as extensively demonstrated in the supporting theory. Overall, our findings highlight a number of important general caveats regarding the nature of mixed Rydberg-valence excited states, their spectral signatures and detection sensitivity in photoionization measurements, and the evaluation of their overall importance in mediating electronic relaxation in a wide range of small model-chromophore systems providing bio-molecular analogues - a topic of considerable interest within the chemical dynamics community over the last decade.

Photoredox-mediated nickel-catalyzed cross-couplings have evolved as a new effective strategy to forge carbon-heteroatom bonds that are difficult to access with traditional methods. Experimental mechanistic studies are challenging because these reactions involve multiple highly reactive intermediates and perplexing reaction pathways, engendering competing, but unverified, proposals for substrate conversions. Here, we report a comprehensive mechanistic study of photoredox nickel-catalyzed C-S cross-coupling based on time-resolved transient absorption spectroscopy, Stern-Volmer quenching, and quantum yield measurements. We have (i) discovered a self-sustained productive Ni(I/III) cycle leading to a quantum yield Φ > 1; (ii) found that pyridinium iodide, formed in situ, serves as the dominant quencher for the excited state photocatalyst and a critical redox mediator to facilitate the formation of the active Ni(I) catalyst; and (iii) observed critical intermediates and determined the rate constants associated with their reactivity. Not only do the findings reveal a complete reaction cycle for C-S cross-coupling, but the mechanistic insights have also allowed for the reaction efficiency to be optimized and the substrate scope to be expanded from aryl iodides to include aryl bromides, thus broadening the applicability of photoredox C-S cross-coupling chemistry.

Oxidation-induced strategy for inert chemical bond activation through highly active radical cation intermediate has exhibited unique reactivity. Understanding the structure and reactivity patterns of radical cation intermediates is crucial in the mechanistic study and will be beneficial for developing new reactions. In this work, the structure and properties of indole radical cations have been revealed using time-resolved transient absorption spectroscopy, in situ electrochemical UV-vis, and in situ electrochemical electron paramagnetic resonance (EPR) technique. Density functional theory (DFT) calculations were used to explain and predict the regioselectivity of several electrochemical oxidative indole annulations. Based on the understanding of the inherent properties of several indole radical cations, two different regioselective annulations of indoles have been successfully developed under electrochemical oxidation conditions. Varieties of furo[2,3-b]indolines and furo[3,2-b]indolines were synthesized in good yields with high regioselectivities. Our mechanistic insights into indole radical cations will promote the further development of oxidation-induced indole functionalizations.

In this work, we report a new photocatalytic system that links multifunctional semiconductor nanocrystals with emerging water-soluble molecular catalysts made of earth-abundant elements for H2 generation [Ni(P2RN2R')2(BF4)2]4-, R = Ph, R' = [PhSO3]- (NiS). This noble metal free hybrid exhibits remarkable catalytic activity with a turnover number of 511 for H2 production and a photon-to-H2 conversion efficiency of 12.5%. The mechanistic insight into such high efficiency in this photocatalytic system was examined using a combination of steady-state emission and time-resolved absorption spectroscopy.

Ras is a key regulator of signal transduction in cells. Ras malfunction is associated with a huge variety of oncological diseases. It is turned off by hydrolysis of bound GTP, which is accelerated by GTPase-activating proteins (GAPs). This minireview discusses the mechanism of Ras-catalyzed GTP hydrolysis, focusing on conformational dynamics and catalytic mechanisms. We discuss structural changes and the role of key residues such as Thr35, Gly60, Tyr32, Gln61, Gly12, and Gly13. Biophysical techniques such as X-ray crystallography, time-resolved FTIR spectroscopy, and hybrid quantum mechanics/molecular mechanics calculations have revealed the detailed reaction mechanisms, including the entry of the arginine finger and the rate-limiting step of inorganic phosphate release. Recent studies on the hydrolysis mechanism favor a solvent-assisted pathway. In addition, we summarize recent advances in Ras-targetingdrugs.

Studying Fe(III)-catalyzed reactions by NMR poses challenges due to the paramagnetic nature of Fe(III) species. Consequently, spin-independent methods for studying iron(III)-catalyzed processes are of significant interest to the iron catalysis community. This work introduces, for the first time, mechanistic insights into two Fe(III)-catalyzed organic reactions using near-IR spectroscopy, which enables the determination of rate constants and the analysis of reaction intermediates. Time-resolved near-IR spectroscopy allows monitoring the formation and disappearance of functional groups, providing data that can be processed similarly to NMR or UV-vis spectroscopy for kinetic studies. Using this approach, rate constants for a Fe(III)-catalyzed Meyer-Schuster rearrangement and Michael additions were determined. Furthermore, near-IR spectra of a mixture of stoichiometric amounts of catalyst and reagent revealed spectral shifts associated with catalyst-substrate interactions, allowing the identification of the part of the substrate activated by the catalyst.