Hydrogen Shift Research Articles

Articaine interaction with phospholipid bilayers

Local anesthetics promote analgesia by interacting with excitable membranes. Articaine (ATC) has a unique composition among local anesthetics as it possesses a thiophene instead of the typical phenyl ring. Aiming to characterize the interaction of neutral articaine (nATC) with phospholipid membranes, we have employed a synergistic approach of experimental and computational techniques. Fluorescence measurements supported nATC partitioning into the membranes, since its intrinsic fluorescence anisotropy increased from 0.03 in water to 0.29 in the presence of egg phosphatidylcholine (EPC) liposomes, and the fluorescence of AHBA, a probe that monitors the water-membrane interface, was quenched by nATC. 1H NMR experiments revealed changes in the chemical shifts of articaine and EPC hydrogens after partitioning, and shorter T1 values of nATC hydrogens when inserted into the EPC vesicles. Contacts of nATC and the phospholipid polar head group were inferred from 2D-NOE. Taken together, these results indicate a superficial insertion of the nATC molecules inside EPC bilayers. This conclusion was confirmed by molecular dynamics simulations, which allowed the identification of the key interactions underlying the preferential location of nATC in the bilayer. Contrary to what is often stated (that articaine is a high lipophilic local anesthetic agent) our results place ATC among the hydrophilic ones, such as lidocaine, prilocaine, and mepivacaine, for which the water/membrane interface is the preferred location.

Reaction kinetics of hydrogen shift isomerization of 1-hexyl radicals

Isomerization reactions form an important class of alkyl reactions. In this work, the kinetics of five types of 1-hexyl radical hydrogen shift reactions, i.e. 1-2, 1-3, 1-4, 1-5 and 1-6 hydrogen shift reactions, were investigated. The electronic structure calculations were performed by M06-2X/6-311 + G(2df,2p), and the high-pressure limit rate constants were obtained by using the conventional transition state theory including the multi-structural torsional anharmonicity and tunneling corrections with the Eckart approximation. The calculated rate coefficients of 1-hexyl radical 1-5 hydrogen shift isomerization agree very well with literature experimental data, which validates our methods. The results show that the 1-5, 1-6, 1-4 hydrogen shift reactions dominate in the low temperature region, and the multi-structural torsional anharmonicity factors of the five 1-hexyl radical isomerization reactions vary from 0.03 to 1.12 and reduce with the increasing ring structure size of the transition states.

The investigation on ibuprofen methyl ester isomerization as a fundamental stage in the preparation of antipyretic medicine (R)-ibuprofen: a computational insight

The isomerization of the widely used nonsteroid anti-inflammatory medicine ibuprofen was investigated by employing the hybrid density functional theory. The rearrangement reaction of (R)-(−)-ibuprofen to its (S)-( +)-isomer consists of a [1,3]-hydrogen shifts. This process causes an inversion of configuration at C7. The obtained results revealed that the rate-limiting step of ibuprofen isomerization is the excitation of (R)-(−)-ibuprofen methyl ester in its initial structure to the first excited singlet state S1 at λ = 231 nm. In addition, the C7-H19 distance was investigated and analyzed for the excited singlet to obtain more information about the isomerization reaction occurring upon excitation. Based upon the calculations, passing through a barrier of around 72 kcal/mol is necessary for this isomerization reaction. Furthermore, the -0.944 kcal/mol of thermodynamic stability of the (S)-( +)-ibuprofen methyl ester elucidates the more photostability of (S)-( +)-ibuprofen methyl ester than (R)-(−)-isomer. The overall reactions with the different components belonging to each reaction step have been fully analyzed.

Oxidation kinetics of n-pentanol: A theoretical study of the reactivity of the 1‑hydroxy‑1-peroxypentyl radical

n-Pentanol has been considered as a promising alternative fuel for compression-ignition engines due to its potential to reduce greenhouse gases and pollutant emissions. Engine performance is strongly dominated by fuel oxidation chemistry, and thus a more accurate determination of the coefficients of the reactions ruling its oxidation is essential for the utilization of n-pentanol in combustion engines. The reactions involving 1‑hydroxy‑1-pentyl and molecular oxygen were found to play an important role in controlling the low temperature oxidation chemistry, but have not been investigated experimentally or theoretically; this is also the case for the reactions of the 1‑hydroxy‑1-peroxypentyl radical, which is formed by the addition of oxygen to the radical center of 1‑hydroxy‑1-pentyl. This work presents a theoretical study with high level ab initio calculations at the CCSD(T)/aug-cc-pVTZ//M06-2X/cc-pVTZ level of theory to shed light on the fate of the 1‑hydroxy‑1-peroxypentyl radical. The rate coefficients of all the possible intra-molecular hydrogen shift reactions of that radical were computed using variational transition state theory with small curvature tunneling corrections. For certain reactions, tunneling and variational effects are very pronounced, proving the need for robust methodologies to account for these effects. The hydrogen shift reaction leading to a concerted HO2 elimination and formation of n-pentanal is the dominant pathway and governs the reactivity of 1‑hydroxy‑1-peroxypentyl radical at any temperature. The reverse of this reaction was thereby investigated as well. For this prominent pathway, the effects of multistructural (multiple conformers) torsional anharmonicity of the stationary points were taken into account in order to refine the forward and reverse rate coefficients. The rate coefficients calculated at room temperature are compared to those calculated using a previously developed cost-effective multi-conformer transition state theory approach. The system-specific quantum Rice-Ramsperger-Kassel (SS-QRRK) theory was used to compute the pressure-dependent rate coefficients, which indicate significant pressure dependence at intermediate and high temperatures. Implementation of the calculated reaction rate coefficients in chemical kinetics models of n-pentanol revealed that our computed rate coefficients enable better insights into the chemistry of n-pentanol, and help to understand how n-pentanal is formed.

Comparative study of p-phenylenediamine antioxidant effectiveness in styrene-butadiene and polyisoprene rubber through NMR calculations

Structures of six p-phenylenediamine (PPD) antioxidants were optimized and their NMR shifts were evaluated by B3LYP calculations. The dependences of experimental values of Antioxidant Effectiveness (AEX) and Molar Antioxidant Effectiveness (AEM) in styrene-butadiene (SBR) and polyisoprene (PIR) rubber on the calculated NMR chemical shifts of nitrogens, tertiary carbons and hydrogens bonded to them were investigated by means of a multiple linear regression analysis. Based on regression parameter values, the significance of the N centers between aromatic rings (A) seems to be higher than of the N centers between aromatic rings and aliphatic chains (B) except AEM data in PIR. The extent of shielding the A center activity by the cumyl group in ortho-position was estimated. Regression parameters obtained for SBR are significantly higher than for PIR.

What a little branching can do – Dissociative photoionization of two butanol isomers

The fragmentation processes of two internal energy-selected C4H10O+ isomers, 1-butanol and isobutanol cations, were investigated by imaging photoelectron photoion coincidence (iPEPICO) spectroscopy. The first dissociation channel leads to the formation of C4H8+ ions (m/z 56) by water loss in both isomers. Using statistical energy distribution and rate models including the isomerization of the parent ion, the 0 K appearance energies (E0) were determined to be 10.347 ± 0.015 eV and 10.57 ± 0.05 eV for 1-butanol and isobutanol, respectively. The second dissociation channel, the formation of CH3OH2+, quickly overtakes the water-loss channel in isobutanol with an E0 of 10.61 ± 0.02 eV. It appears only as a minor channel in 1-butanol with an E0 of 10.74 ± 0.09 eV. The methanol-loss channel, forming propylene ion, opens up at E0 = 10.94 ± 0.04 eV and 10.72 ± 0.02 eV in 1-butanol and isobutanol, respectively. The next two fragmentation pathways correspond to complementary pair formation of C3H7(+/o) and CH2OH(o/+). The former is assigned as the isopropyl (ion) in both butanol isomers. The channel corresponds to simple bond cleavage in isobutanol with the E0 difference corresponding to the ionization energy difference of the fragments at E0 = 10.97 ± 0.05 eV (C3H7+) and at E0 = 11.11 ± 0.20 eV (CH2OH+). However, there is an internal hydrogen shift necessary in 1-butanol and, therefore, the complementary ions appear at the same E0 = 11.10 ± 0.03 eV, which corresponds to a shared rate limiting transition state. The sequential dissociation product from m/z 56, C3H5+, appears above 11.6 eV as a minor channel in both isomers. Finally, we determined −279.1 ± 1.6 kJ mol−1 as the 298 K heat of formation of gaseous isobutanol. We also propose revised ionization energies for the two butanols isomers based on composite method calculations.

Importance of isomerization reactions for OH radical regeneration from the photo-oxidation of isoprene investigated in the atmospheric simulation chamber SAPHIR

Abstract. Theoretical, laboratory, and chamber studies have shown fast regeneration of the hydroxyl radical (OH) in the photochemistry of isoprene, largely due to unimolecular reactions which were previously thought not to be important under atmospheric conditions. Based on early field measurements, nearly complete regeneration was hypothesized for a wide range of tropospheric conditions, including areas such as the rainforest where slow regeneration of OH radicals is expected due to low concentrations of nitric oxide (NO). In this work the OH regeneration in isoprene oxidation is directly quantified for the first time through experiments covering a wide range of atmospherically relevant NO levels (between 0.15 and 2 ppbv – parts per billion by volume) in the atmospheric simulation chamber SAPHIR. These conditions cover remote areas partially influenced by anthropogenic NO emissions, giving a regeneration efficiency of OH close to 1, and areas like the Amazonian rainforest with very low NO, resulting in a surprisingly high regeneration efficiency of 0.5, i.e. a factor of 2 to 3 higher than explainable in the absence of unimolecular reactions. The measured radical concentrations were compared to model calculations, and the best agreement was observed when at least 50 % of the total loss of isoprene peroxy radicals conformers (weighted by their abundance) occurs via isomerization reactions for NO lower than 0.2 ppbv. For these levels of NO, up to 50 % of the OH radicals are regenerated from the products of the 1,6 α-hydroxy-hydrogen shift (1,6-H shift) of Z-δ-RO2 radicals through the photolysis of an unsaturated hydroperoxy aldehyde (HPALD) and/or through the fast aldehydic hydrogen shift (rate constant ∼10 s−1 at 300 K) in di-hydroperoxy carbonyl peroxy radicals (di-HPCARP-RO2), depending on their relative yield. The agreement between all measured and modelled trace gases (hydroxyl, hydroperoxy, and organic peroxy radicals, carbon monoxide, and the sum of methyl vinyl ketone, methacrolein, and hydroxyl hydroperoxides) is nearly independent of the adopted yield of HPALD and di-HPCARP-RO2 as both degrade relatively fast (<1 h), forming the OH radical and CO among other products. Taking into consideration this and earlier isoprene studies, considerable uncertainties remain on the distribution of oxygenated products, which affect radical levels and organic aerosol downwind of unpolluted isoprene-dominated regions.

N,N'-Ethylene-Bridged Bis-2-Aryl-Pyrrolinium Cations to E-Diaminoalkenes: Non-Identical Stepwise Reversible Double-Redox Coupled Bond Activation Reactions.

This work presents a stepwise reversible two‐electron transfer induced hydrogen shift leading to the conversion of a bis‐pyrrolinium cation to an E‐diaminoalkene and vice versa. Remarkably, the forward and the reverse reaction, which are both reversible, follow two completely different reaction pathways. Establishing such unprecedented property in this type of processes was possible by developing a novel synthetic route towards the starting dication. All intermediates involved in both the forward and the backward reactions were comprehensively characterized by a combination of spectroscopic, crystallographic, electrochemical, spectroelectrochemical, and theoretical methods. The presented synthetic route opens up new possibilities for the generation of multi‐pyrrolinium cation scaffold‐based organic redox systems, which constitute decidedly sought‐after molecules in contemporary chemistry.

1,2-Thiaphosphetanes: The Quest for Wittig-Type Ring Cleavage, Rearrangement, and Sulfur Atom Transfer

The potential energy surface for opening and ring-enlargement reactions of 1,2-thiaphosphetane with different oxidation states and coordination at phosphorus has been computationally explored. The most favored [2 + 2] cycloreversions are the so-called normal Wittig-type reactions furnishing an alkene and a P═S-containing component. Somewhat unfavored are reactions involving the P-S bond cleavage and a C-to-P hydrogen shift as well as a ring enlargement to a 1,3,2-dithiaphospholane in the case of high coordinate derivatives. Apart from a two-step P-to-S oxygen transfer in 1,2σ4λ5-thiaphosphetane P-oxide, an interesting reaction is the P-S bond cleavage leading to a thiabetaine which, alternatively, can be formed by the C-attack of a phosphinidene oxide on a thiirane. A similar route, energetically more favored, was found for 1,2σ5λ5-thiaphosphetane starting from thiirane and the corresponding phosphane. For a wide set of P(III) reagents including HPR2 (R = Me, Ph), PR3 (R = Me, Ph, NMe2, OMe, F, Cl), and HP═O, the competitive direct S-attack was found to be the preferred pathway for the desulfurization of thiiranes, and the relative tendency for these P(III) reagents to act as an S-atom acceptor, the thermodynamic S-transfer potential (TSP) scale, was defined using the S8/S7 couple as a point of reference.

Effects of electrostatic drag on the velocity of hydrogen migration - pre- and post-transition state enthalpy/entropy compensation.

Ab initio molecular dynamics calculations were used to explore the underlying factors that modulate the velocity of hydrogen migration for 1,2 hydrogen shifts in carbocations in which different groups interact noncovalently with the migrating hydrogen. Our results indicate that stronger electrostatic interactions between the migrating hydrogen and nearby π-systems lead to slower hydrogen migration, an effect tied to entropic contributions from the hydrogen + neighboring group substructures.

Tensor meson contribution to the Lamb shift and hyperfine splitting in muonic hydrogen

We calculate the tensor meson exchange contribution to the interaction operator of muon and proton, which is determined by the tensor meson coupling with two photon state. For the construction of transition form factor T → γγ we use the monopole parametrization over photon four-momenta and experimental data on the decay width ΓTγγ. It is shown that tensor meson f2(1270) exchange gives essential contribution to the Lamb shift in muonic hydrogen ΔΕLs (2P – 2S) which should be taken into account for a comparison with precise experimental data.

Hydrolysis of ketene catalysed by nitric acid and water in the atmosphere

Environmental contextThe detailed mechanism of hydrolysis of gas-phase ketene to form acetic acid is critical for understanding the formation of certain atmospheric contaminants. This study explores the effect of nitric acid and water on the hydrolysis of ketene in the atmosphere. The calculated results show that nitric acid is an effective catalyst in the hydrolysis of ketene to form acetic acid in atmospheric water-restricted environments. AbstractThe gas-phase hydrolysis of ketene and the unimolecular reaction of 1,1-enediol catalysed by nitric acid and water have been investigated using quantum chemical methods and conventional transition state theory with Eckart tunnelling. The theoretical calculation results show that nitric acid exerts a strong catalytic effect on the hydrolysis of ketene in the gas-phase. The calculated energy barrier for the direct reaction mechanistic pathway is reduced from 42.10kcal mol−1 in the reaction of ketene with water to 3.40kcal mol−1 in the reaction of ketene with water catalysed by HNO3. The catalytic ability of nitric acid is further proven in the hydrogen shift reaction of 1,1-enediol because the energy barrier of the unimolecular reaction of 1,1-enediol is decreased from 44.92kcal mol−1 to −4.51kcal mol−1. In addition, the calculated results indicate that there is competition between the direct and indirect mechanistic pathways with the increase of additional water molecules in the reaction of ketene with water catalysed by HNO3 and (H2O)n (n=1, 2). The calculated kinetics results show that the CH2=C=O+H2O+HNO3 reaction is significant in the gas phase of the atmosphere and the other reactions are negligible owing to the slow reaction rates. However, compared with the CH2=C=O+OH reaction, the CH2=C=O+H2O+HNO3 reaction is very slow and cannot compete with the CH2=C=O+OH reaction. CH2=C=O+OH is the main elimination pathway of ketene in the gas phase of the atmosphere. Our findings reveal that acetic acid may be formed through the hydrolysis of ketene in atmospheric water-restricted environments of the surfaces of aqueous, aerosol and cloud droplets.

Syntheses of Benzofuranoquinolines and Analogues via Photoinduced Acceptorless Dehydrogenative Annulation of o-Phenylfuranylpyridines.

A strategy for the syntheses of benzofuranoquinolines and its analogues via the irradiation of o-phenylfuranyl/thienylpyridines/pyrimidines in DCM with UV light at rt under an argon atmosphere is described. The mechanism of this reaction through the process of 6π-electrocyclization, [1,5]-hydrogen shift, and 1,3-eneamine tautomerism leading to H2 evolution was elucidated. Notably, the syntheses of cis-8b-methyl-8b,13a-dihydrobenzo[f]benzofuro[3,2-h]quinolone via the photoinduced rearrangement of 2-(3-methylbenzofuran-2-yl)-3-phenylpyridine relevant to the mechanism of this reaction highlights the importance of the developed methodology.

Stereoselectivity in Atmospheric Autoxidation

We show that the diastereomers of hydroxy peroxy radicals formed from OH and O2 addition to C2 and C3, respectively, of crotonaldehyde (CH3CHCHCHO) undergo gas-phase unimolecular aldehydic hydrogen shift (H-shift) chemistry with rate coefficients that differ by an order of magnitude. The stereospecificity observed here for crotonaldehyde is general and will lead to a significant diastereomeric-specific chemistry in the atmosphere. This enhancement of specific stereoisomers by stereoselective gas-phase reactions could have widespread implications given the ubiquity of chirality in nature. The H-shift rate coefficients calculated using multiconformer transition state theory (MC-TST) agree with those determined experimentally using stereoisomer-specific gas-chromatography chemical ionization mass spectroscopy (GC-CIMS) measurements.

Higher-order logarithmic corrections and the two-loop self-energy of a 1s electron in hydrogen

The leading computational QED uncertainty of the Lamb shift in the $1s$ state in the hydrogen atom and helium ion is due to two-loop pure self-energy contributions. An exact evaluation in $Z\ensuremath{\alpha}$ has not yet been performed for $Z=1,2$, while a calculation based on the $Z\ensuremath{\alpha}$ expansion has a limited accuracy. To improve it, we calculate a leading logarithmic contribution in order ${\ensuremath{\alpha}}^{2}{(Z\ensuremath{\alpha})}^{8}m$ and estimate the nonleading subterms in orders ${\ensuremath{\alpha}}^{2}{(Z\ensuremath{\alpha})}^{7}m$ and ${\ensuremath{\alpha}}^{2}{(Z\ensuremath{\alpha})}^{8}m$. To further improve the accuracy, we take advantage of a combined evaluation of the numerical results of the exact calculations in $Z\ensuremath{\alpha}$ performed at $Z=10--30$, and the results of the $Z\ensuremath{\alpha}$ expansion in order to reach the most accurate result, which can be done by fitting the data. The quality of the fit, including its reliability and accuracy, strongly depends on a theoretical input, which is the main target of this paper. Strictly speaking, we develop not a fit, but a theoretical approximation for the pure self-energy contribution, which may serve as a base for a robust fit. It is also important to estimate a deviation of the truncated function from the true one. For this purpose, we calculate the leading logarithmic term and estimate the subleading ones in order ${\ensuremath{\alpha}}^{2}{(Z\ensuremath{\alpha})}^{9}m$. That allows us to find a reliable result which is more accurate than both fits over the numerical data and the results from the $Z\ensuremath{\alpha}$ expansion, which have been previously considered in literature. Performing the fit procedures, we focus our attention on the theoretical input which plays an essential role in the reliability and accuracy of the fit. Our results for the two-loop pure self-energy contribution to the $1s$ Lamb shift are expressed in a standard notation as ${B}_{60}=\ensuremath{-}72(7),\phantom{\rule{0.28em}{0ex}}{G}_{60}(Z=1)=\ensuremath{-}80(6)$, and ${G}_{60}(Z=2)=\ensuremath{-}83(5)$. That significantly improves the theoretical accuracy of the $1s$ Lamb shift in hydrogen, deuterium, and in the helium ions.

Unraveling the proton puzzle

Atomic Physics The discrepancy between the proton size deduced from the Lamb shift in muonic hydrogen and the average, textbook value based on regular (electronic) hydrogen has puzzled physicists for nearly a decade. One possible resolution could be that electrons interact with protons in a different way than muons do, which would require “new physics.” Bezginov et al. measured the Lamb shift in electronic hydrogen, which allowed for a direct comparison to the Lamb shift measured in muonic hydrogen. The two results agreed, but the discrepancy with the averaged value remains. Science , this issue p. [1007][1] [1]: /lookup/doi/10.1126/science.aau7807

A measurement of the atomic hydrogen Lamb shift and the proton charge radius.

The surprising discrepancy between results from different methods for measuring the proton charge radius is referred to as the proton radius puzzle. In particular, measurements using electrons seem to lead to a different radius compared with those using muons. Here, a direct measurement of the n = 2 Lamb shift of atomic hydrogen is presented. Our measurement determines the proton radius to be r p = 0.833 femtometers, with an uncertainty of ±0.010 femtometers. This electron-based measurement of r p agrees with that obtained from the analogous muon-based Lamb shift measurement but is not consistent with the larger radius that was obtained from the averaging of previous electron-based measurements.

A new model mechanism for atmospheric oxidation of isoprene: global effects on oxidants, nitrogen oxides, organic products, and secondary organic aerosol

Abstract. Atmospheric oxidation of isoprene, the most abundantly emitted non-methane hydrocarbon, affects the abundances of ozone (O3), the hydroxyl radical (OH), nitrogen oxide radicals (NOx), carbon monoxide (CO), oxygenated and nitrated organic compounds, and secondary organic aerosol (SOA). We analyze these effects in box models and in the global GEOS-Chem chemical transport model using the new reduced Caltech isoprene mechanism (RCIM) condensed from a recently developed explicit isoprene oxidation mechanism. We find many similarities with previous global models of isoprene chemistry along with a number of important differences. Proper accounting of the isomer distribution of peroxy radicals following the addition of OH and O2 to isoprene influences the subsequent distribution of products, decreasing in particular the yield of methacrolein and increasing the capacity of intramolecular hydrogen shifts to promptly regenerate OH. Hydrogen shift reactions throughout the mechanism lead to increased OH recycling, resulting in less depletion of OH under low-NO conditions than in previous mechanisms. Higher organonitrate yields and faster tertiary nitrate hydrolysis lead to more efficient NOx removal by isoprene and conversion to inorganic nitrate. Only 20 % of isoprene-derived organonitrates (excluding peroxyacyl nitrates) are chemically recycled to NOx. The global yield of formaldehyde from isoprene is 22 % per carbon and less sensitive to NO than in previous mechanisms. The global molar yield of glyoxal is 2 %, much lower than in previous mechanisms because of deposition and aerosol uptake of glyoxal precursors. Global production of isoprene SOA is about one-third from each of the following: isoprene epoxydiols (IEPOX), organonitrates, and tetrafunctional compounds. We find a SOA yield from isoprene of 13 % per carbon, much higher than commonly assumed in models and likely offset by SOA chemical loss. We use the results of our simulations to further condense RCIM into a mini Caltech isoprene mechanism (Mini-CIM) for less expensive implementation in atmospheric models, with a total size (108 species, 345 reactions) comparable to currently used mechanisms.

11B NMR Chemical Shift Predictions via Density Functional Theory and Gauge-Including Atomic Orbital Approach: Applications to Structural Elucidations of Boron-Containing Molecules.

11B nuclear magnetic resonance (NMR) spectroscopy is a useful tool for studies of boron-containing compounds in terms of structural analysis and reaction kinetics monitoring. A computational protocol, which is aimed at an accurate prediction of 11B NMR chemical shifts via linear regression, was proposed based on the density functional theory and the gauge-including atomic orbital approach. Similar to the procedure used for carbon, hydrogen, and nitrogen chemical shift predictions, a database of boron-containing molecules was first compiled. Scaling factors for the linear regression between calculated isotropic shielding constants and experimental chemical shifts were then fitted using eight different levels of theory with both the solvation model based on density and conductor-like polarizable continuum model solvent models. The best method with the two solvent models yields a root-mean-square deviation of about 3.40 and 3.37 ppm, respectively. To explore the capabilities and potential limitations of the developed protocols, classical boron–hydrogen compounds and molecules with representative boron bonding environments were chosen as test cases, and the consistency between experimental values and theoretical predictions was demonstrated.

Mechanistic study of fenoprofen photoisomerization to pure (S)-fenoprofen: a DFT study

This work provides a comprehensive DFT study on the conversion mechanism and photoisomerization of the effective and commonly used nonsteroidal anti-inflammatory medicine fenoprofen. The results obtained exhibit that the rearrangement procedure of (R)-fenoprofen to its (S)-enantiomer occurs in [1,3]-hydrogen shifts with inversion of configuration at chiral center C8. According to the computed energies, we can find out that the excitation of (R)-fenoprofen methyl ester in its primary form to the first excited singlet state S1 at λ = 240 nm is the rate-limiting step of photoisomerization of fenoprofen. In order to obtain further insight into the isomerization process occurring upon excitation, this process was studied by scanning the C8-H11 distance for the excited singlet. Our calculations revealed that the isomerization process requires passing a barrier of approximately 84 kcal/mol. Furthermore, the more photostability of (S)-fenoprofen methyl ester than that of its related (R)-enantiomer can be attributed to the − 1.34 kcal/mol of thermodynamic stability of the (S)-fenoprofen methyl ester.