Dynamics of photodissociation of nitric oxide from S-nitrosylated cysteine and N-acetylated cysteine derivatives in water.

Cysteine and N-acetylated cysteine derivatives are ubiquitous in biological systems; they have thiol groups that bind NO to form S-nitrosothiols (RSNOs) such as S-nitrosocysteine (CySNO), S-nitroso-N-acetylcysteine (NacSNO), and S-nitroso-N-acetylpenicillamine (NapSNO). Although they have been utilised as thermally or catalytically decomposing NO donors, their photochemical applications are yet to be fully explored owing to the lack of photodissociation dynamics. To this end, the photoexcitation dynamics of these RSNOs in water at 330 nm were investigated using femtosecond time-resolved infrared (TRIR) spectroscopy over a broad time range encompassing the entire reaction, which includes the primary reaction, secondary reactions of the reaction intermediates, and product formation. We discovered that the acetate and amide groups in these RSNOs have strong vibrational bands sensitive to the bondage of NO and the electronic state of the compound, which facilitates the identification of reaction intermediates involved in photoexcitation. The simplest thiol available with the acetate group-thioglycolic acid-was nitrosylated; it produced S-nitrosothioglycolic acid (TgSNO) and was comparatively investigated. Transient absorption bands in the TRIR spectra of the RSNOs were assigned using quantum chemical calculations. Photoexcited cysteine-related RSNOs either decompose into RS and NO within 0.3 ps after excitation at 330 nm with a primary quantum yield (Φ1) of 0.46-1 or relax into an electronically excited intermediate state lying at 42 ± 3 kcal mol-1 above the ground state, which relaxes into the ground state with a time constant of 460-520 ps. A majority (62-80%) of the RS radical geminately rebinds with NO at a time constant of 3-7 ps. The remaining RS reacts with the neighbouring RSNO, which produces additional NO and RSSR with a (nearly) diffusion-limited rate constant that doubles the amount of NO produced; further, it remarkably extends the time window for the dissociated NO to react with the target compound. The final fraction of NO produced from these RSNOs at 330 nm was 0.32-0.58, and it depends on the geminate rebinding yield and Φ1. The detailed dynamics of the photoexcited RSNO can be utilised in the quantitative application of these RSNOs in practical use and in the synthesis of more efficient photoactivated NO precursors.

Complete photodissociation dynamics of CF2I2 in solution.

Photodissociation dynamics of CF2I2 in cyclohexane were evaluated by probing the C-F stretching mode over a wide time range after ultraviolet excitation using femtosecond infrared spectroscopy. After the ultrafast (<0.2 ps) state-selective photodissociation of CF2I2 as in the gas phase (267 nm excitation led to exclusive three-body dissociation (CF2 + I + I), 350 nm to exclusive two-body dissociation (CF2I + I), and 310 nm to a mixture of three- and two-body dissociations), various secondary reactions were observed. Once produced, some nascent CF2 radicals immediately formed a complex with the departing I atom (ICF2), which produced either CF2I or CF2 radicals. The produced CF2I geminately recombined with the I atom, whereas the CF2 radical reacted bimolecularly to produce C2F4 with a diffusion-limited rate constant of 8.1 × 109 M-1 s-1. Some nascent CF2I radicals were produced with sufficient excess energy to further dissociate into CF2 and I, or immediately reacted with the dissociated I atom to form the I2-CF2 isomer that rapidly dissociated into CF2 and I2. Other nascent CF2I radicals geminately recombined with the I atom with various time constants. Thus, the nascent photoproducts, CF2 and CF2I take various reaction paths: complex formation, secondary dissociation, isomer formation, and fast and slow germinate rebindings. The ensuing reaction path of the nascent photoproduct is dictated by its internal energy as well as solvent environment, which leads to different interactions between the photoproduct and solvent. Measurement over a broad time range with a structure-sensitive probe could reveal the fate of all the reaction intermediates, which allows evaluation of the complete reaction dynamics in solution.

Dynamics of Irreversible NO Release from Photoexcited Molsidomine.

Molsidomine (SIN-10), an orally administered NO-delivery drug for vasodilation, cannot be used to alleviate hypertensive crisis because it releases NO at a slow rate. SIN-10 may be used to treat sudden cardiac abnormalities if the rapid and immediate release of NO is achieved via photoactivation. The photodissociation dynamics associated with the NO release process from SIN-10 in CHCl3 was investigated using time-resolved infrared spectroscopy. Approximately 41% of photoexcited SIN-10 at 360 nm decomposed into CO2, CH2CH3 radical, and the remaining radical fragment [SIN-1A(-H)] with a time constant of 43 ps. All SIN-1A(-H) released NO spontaneously with a time constant of 68 ns, becoming N-morpholino-aminoacetonitrile, resulting in 41% for the quantum yield of immediate NO release from SIN-10. The results obtained can be used to realize the quantitative control of the NO administration at a specific time, and SIN-10 can be potentially used to address the phenomenon of hypertensive crisis.

Rotational Isomerization of Carbon-Carbon Single Bonds in Ethyl Radical Derivatives in a Room-Temperature Solution.

The rotational isomerization of 1,2-disubstituted ethyl radical derivatives, reaction intermediates often found in the reaction of 1,2-disubstituted ethane derivatives, has never been measured because of their short lifetime and ultrafast rotation. However, the rotational time constant is critical for understanding the detailed reaction mechanism involving these radicals, which determine the stereoisomers of compounds produced via the intermediates. Using time-resolved infrared spectroscopy, we found that the CF2BrCF2 radical in a CCl4 solution rotationally isomerizes with a time constant of 47 ± 5 ps at 280 ± 2 K. From this value and the rotational barrier heights of related compounds, CH3CH2 and CH3CH2CHCH3 radicals in CCl4 were estimated to rotationally isomerize within 1 ps at 298 K, considerably faster than ethane and n-butane, which rotationally isomerize with time constants of 1.8 and 81 ps, respectively. The time constant for the rotational isomerization was similar to that calculated using transition state theory with a transmission coefficient of 0.75.

Photodissociation Dynamics of Nitric Oxide from N-Acetylcysteine- or N-Acetylpenicillamine-bound Roussin's Red Ester.

The photochemical release of nitric oxide (NO) from a NO precursor is advantageous in terms of spatial, temporal, and dosage control of NO delivery to target sites. To realize full control of the quantitative NO administration from photoactivated NO precursors, it is necessary to have detailed dynamical information on the photodissociation of NO from NO precursors. We synthesized two new water-soluble Roussin's red esters (RREs), [Fe2(µ-N-acetylcysteine)2(NO)4] and [Fe2(µ-N-acetylpenicillamine)2(NO)4], which have five times longer lifetime than the well-known [Fe2(µ-cysteine)2(NO)4]. The photodissociation dynamics of NO from these RREs in water were investigated over a broad time range from 0.3 ps to 10 µs after excitation at 310 and 400 nm using femtosecond time-resolved infrared (IR) spectroscopy. When these RREs are excited, they either release one NO, producing a radical species deficient in one NO (R), [Fe2(µ-RS)2(NO)3], or relax into the ground state without photodeligation via an electronically excited intermediate state (M). R appears immediately after photoexcitation, suggesting that one NO is photodissociated faster than 0.3 ps. A certain fraction of R undergoes geminate recombination (GR) with NO with a time constant of 7-9 ps, while the remaining R competitively binds to the solvent. Solvent-bound R eventually bimolecularly recombines with NO with a rate constant of (1.3-1.6) × 108 M-1 s-1. For a given RRE molecule, the fractional yield of M (0.62-0.76) depends on the excitation wavelength (λex); however, the relaxation time of M (6 ± 1 ns) is independent of λex. Although the primary quantum yield of NO photodissociation (Φ1) was found to be 0.24-0.38, the final yield of NO suitable for other reactions (Φ2) was reduced to 0.14-0.29 due to the picosecond GR of the dissociated NO with R. Detailed photoexcitation dynamics of RRE can be utilized in the quantitative control of NO administration at a specific site and time, promoting pin-point usage of NO in chemistry and biology. We demonstrate that femtosecond IR spectroscopy combined with quantum chemical calculations is a powerful method for obtaining detailed dynamic information on photoactivated NO precursors such as Φ1 and Φ2, the GR yield, and secondary reactions of the nascent photoproducts, which are essential information for the design of efficient photoactivated NO precursors and their quantitative utilization.

Photorelease Dynamics of Nitric Oxide from Cysteine-Bound Roussin's Red Ester.

Nitric oxide (NO) can either boost or impede the growth of cancer cells depending on its concentration. Therefore, any anticancer treatment using NO requires precisely controlled NO administration to the target cells in terms of dosage and timing. In this context, photochemically activated NO donors were actively explored, but their detailed NO-releasing dynamics, which is crucial for their use, is not known yet. We determined detailed photoexcitation dynamics of a stable, nontoxic, and water-soluble NO precursor, cysteine-bound Roussin's Red Ester (Cys-RRE), including secondary reactions of the nascent photoproducts. The primary quantum yields of the NO dissociation from the photoexcited Cys-RRE were found to be 24-54% depending on the excitation wavelength; however, the geminate rebinding of NO with the nascent radical reduced the level of biologically available NO to as low as 12%. Such information is useful to achieve efficient NO delivery to practical chemical and biological targets.

Conformer-Specific Photodissociation Dynamics of CF2ICF2I in Solution Probed by Time-Resolved Infrared Spectroscopy.

The photodissociation dynamics of CF2ICF2I in solution was investigated from 0.3 ps to 100 µs, after the excitation of CF2ICF2I with a femtosecond UV pulse. Upon excitation, one I atom is eliminated within 0.3 ps, producing a haloethyl radical having a classical structure: anti-CF2ICF2 and gauche-CF2ICF2. All the nascent gauche-CF2ICF2 radicals reacted with the dissociated I atom within the solvent cage to produce a complex, I2··C2F4, in <1 ps. The quasi-stable I2··C2F4 complex in CCl4 (CH3CN or CD3OH) further dissociated into I2 and C2F4 with a time constant of 180 ± 5 (46 ± 3) ps. Some of the anti-CF2ICF2 radicals also formed the I2··C2F4 complex with a time constant of 1.5 ± 0.3 ps, while the remaining radicals underwent secondary elimination of I atom in a few nanoseconds. The time constant for the secondary dissociation of I atom from the anti-CF2ICF2 radical was independent of the excitation wavelength, indicating that the excess energy in the nascent radical is relaxed and that the secondary dissociation proceeds thermally. The formation of the I2··C2F4 complex and the thermal dissociation of the anti-CF2ICF2 radical clearly demonstrate that even a weakly interacting solvent plays a significant role in the modification and creation of reaction.