RNA Environment Is Responsible for Decreased Photostability of Uracil

UV light can induce chemical reactions in nucleic acids and thereby damage the genetic code. Like all of the five primary nucleobases, the isolated RNA base uracil exhibits ultrafast, nonradiative relaxation after photoexcitation, which helps to avoid photodamage most of the time. Nevertheless, within RNA and DNA strands, commonly occurring photolesions have been reported and are often ascribed to long-lived and delocalized excited states. Our quantum dynamical study now shows that excited-state longevity can also occur on a single nucleobase, without the need for delocalization. We include the effects of an atomistic RNA surrounding in wave packet simulations and explore the photorelaxation of uracil in its native biological environment. This reveals that steric hindrance through embedding in an RNA strand can inhibit the ultrafast relaxation mechanism of uracil, promoting excited-state longevity and potential photodamage. This process is nearly independent from the specific combination of neighboring bases

RNA Environment Is Responsible for Decreased Photostability of Uracil

UV light can induce chemical reactions in nucleic acids and thereby damage the genetic code. Like all of the five primary nucleobases, the isolated RNA base uracil exhibits ultrafast, nonradiative relaxation after photoexcitation, which helps to avoid photodamage most of the time. Nevertheless, within RNA and DNA strands, commonly occurring photolesions have been reported and are often ascribed to long-lived and delocalized excited states. Our quantum dynamical study now shows that excited-state longevity can also occur on a single nucleobase, without the need for delocalization. We include the effects of an atomistic RNA surrounding in wave packet simulations and explore the photorelaxation of uracil in its native biological environment. This reveals that steric hindrance through embedding in an RNA strand can inhibit the ultrafast relaxation mechanism of uracil, promoting excited-state longevity and potential photodamage. This process is nearly independent from the specific combination of neighboring bases

Thirtieth Annual Report of the Board of Education, together with the Thirtieth Annual Report of the Secretary of the Board (1866)

Public document no. 2

RNA Environment Is Responsible for Decreased Photostability of Uracil

UV light can induce chemical reactions in nucleic acids and thereby damage the genetic code. Like all of the five primary nucleobases, the isolated RNA base uracil exhibits ultrafast, nonradiative relaxation after photoexcitation, which helps to avoid photodamage most of the time. Nevertheless, within RNA and DNA strands, commonly occurring photolesions have been reported and are often ascribed to long-lived and delocalized excited states. Our quantum dynamical study now shows that excited-state longevity can also occur on a single nucleobase, without the need for delocalization. We include the effects of an atomistic RNA surrounding in wave packet simulations and explore the photorelaxation of uracil in its native biological environment. This reveals that steric hindrance through embedding in an RNA strand can inhibit the ultrafast relaxation mechanism of uracil, promoting excited-state longevity and potential photodamage. This process is nearly independent from the specific combination of neighboring bases

Ground and Excited State Surfaces for the Photochemical Bond Cleavage in Phenylmethylphenylphosphonium Ions

Photolytic bond cleavage is a well-established method to generate carbocations for organic synthesis. Changes in the leaving group have a large influence on the chemical yield. The underlying potential energy surfaces governing the initial process are mostly unknown. We provide potential energy surfaces of ground and excited states on the CASSCF/CASPT2 level of theory for the charged precursor phenylmethylphenylphosphonium ion. We present the electronic and structural changes accompanying the excitation process and the subsequent bond cleavage. Inter-ring charge-transfer processes play a crucial role in the Franck–Condon region. Beyond the Franck–Condon region, competing reaction pathways emerge connected through conical intersections. The phenylmethylphenylphosphonium ion is used as a model system for the commonly used diphenylmethyltriphenylphosphonium ion. The appropriateness of the model is tested by CC2 calculations of the excitation spectrum

Quantum Dynamics in an Explicit Solvent Environment: A Photochemical Bond Cleavage Treated with a Combined QD/MD Approach

In quantum chemistry methods to describe environmental effects on different levels of complexity are available in the common program packages. Electrostatic effects of a solvent for example can be included in an implicit or explicit way. For chemical reactions with large structural changes additional mechanical effects come into play. Their treatment within a quantum dynamical context is a major challenge, especially when excited states are involved. Recently, we introduced a method that realizes an implicit description. Here, we present an approach combining quantum dynamics and molecular dynamics. It explicitly incorporates the solvent environment, whereby the electrostatic as well as the dynamic effects are captured. This new method is demonstrated for the ultrafast photoinduced bond cleavage of diphenylmethylphosphonium ions (Ph₂CH–PPh₃⁺), a common precursor to generate reactive carbocations in solution

Controlling Photorelaxation in Uracil with Shaped Laser Pulses: A Theoretical Assessment

The RNA nucleobase uracil can suffer from photodamage when exposed to UV light, which may lead to severe biological defects. To prevent this from happening in most cases, uracil exhibits an ultrafast relaxation mechanism from the electronically excited state back to the ground state. In our theoretical work, we demonstrate how this process can be significantly influenced using shaped laser pulses. This not only sheds new light on how efficient nature is in preventing biologically momentous photodamage. We also show a way to entirely prevent photorelaxation by preparing a long-living wave packet in the excited state. This can enable new experiments dedicated to finding the photochemical pathways leading to uracil photodamage. The optimized laser pulses we present fulfill all requirements to be experimentally accessible

Buildup and Decay of the Optical Absorption in the Ultrafast Photo-Generation and Reaction of Benzhydryl Cations in Solution

The identification of the transition state or a short-lived intermediate of a chemical reaction is essential for the understanding of the mechanism. For a direct identification typically transient optical spectroscopy is used, preferentially with high temporal resolution. We combine broad-band femtosecond transient absorption measurements and on-the-fly molecular dynamics calculations to decipher the microscopic evolution of the geometry and solvation of photogenerated benzhydryl cations (Ar₂CH⁺, Ar = phenyl, <i>p</i>-tolyl, <i>m</i>-fluorophenyl, or <i>m</i>,<i>m</i>′-difluorophenyl) in bulk solution. From the high level quantum chemical calculations on the microsolvated cation we can deduce a narrowing and blue shift of the cation absorption that is nearly quantitatively equal to the experimental finding. The roughly 300 fs initial increase in the absorption signal found for all investigated combinations of benzhydryl chlorides or phosphonium salts as benzhydryl cation precursors and solvents is therefore assigned to the planarization and solvation of the nascent fragment of the bond cleavage. The actual cleavage time cannot directly be deduced from the rise of the spectroscopic signal. For alcohols as solvent, the cation combines on the picosecond time scale either with one of the solvent molecules to the ether or to a lesser degree geminately with the leaving group. The study shows that the absorption signal attributable to a species like the benzhydryl cation does not mirror the concentration during the first instances of the process. Rather, the signal is determined by the geometrical relaxation of the photoproduct and the response of the solvent

Buildup and Decay of the Optical Absorption in the Ultrafast Photo-Generation and Reaction of Benzhydryl Cations in Solution

The identification of the transition state or a short-lived intermediate of a chemical reaction is essential for the understanding of the mechanism. For a direct identification typically transient optical spectroscopy is used, preferentially with high temporal resolution. We combine broad-band femtosecond transient absorption measurements and on-the-fly molecular dynamics calculations to decipher the microscopic evolution of the geometry and solvation of photogenerated benzhydryl cations (Ar₂CH⁺, Ar = phenyl, <i>p</i>-tolyl, <i>m</i>-fluorophenyl, or <i>m</i>,<i>m</i>′-difluorophenyl) in bulk solution. From the high level quantum chemical calculations on the microsolvated cation we can deduce a narrowing and blue shift of the cation absorption that is nearly quantitatively equal to the experimental finding. The roughly 300 fs initial increase in the absorption signal found for all investigated combinations of benzhydryl chlorides or phosphonium salts as benzhydryl cation precursors and solvents is therefore assigned to the planarization and solvation of the nascent fragment of the bond cleavage. The actual cleavage time cannot directly be deduced from the rise of the spectroscopic signal. For alcohols as solvent, the cation combines on the picosecond time scale either with one of the solvent molecules to the ether or to a lesser degree geminately with the leaving group. The study shows that the absorption signal attributable to a species like the benzhydryl cation does not mirror the concentration during the first instances of the process. Rather, the signal is determined by the geometrical relaxation of the photoproduct and the response of the solvent

Unravelling Photochemical Relationships Among Natural Products from <i>Aplysia dactylomela</i>

Aplydactone (<b>1</b>) is a brominated ladderane sesquiterpenoid that was isolated from the sea hare <i>Aplysia dactylomela</i> together with the chamigranes dactylone (<b>2</b>) and 10-<i>epi</i>-dactylone (<b>3</b>). Given the habitat of <i>A. dactylomela</i>, it seems likely that <b>1</b> is formed from <b>2</b> through a photochemical [2 + 2] cycloaddition. Here, we disclose a concise synthesis of <b>1</b>, <b>2</b>, and <b>3</b> that was guided by excited state theory and relied on several highly stereoselective transformations. Our experiments and calculations confirm the photochemical origin of <b>1</b> and explain why it is formed as the sole isomer. Irradiation of <b>3</b> with long wavelength UV light resulted in a [2 + 2] cycloaddition that proceeded with opposite regioselectivity. On the basis of this finding, it seems likely that the resulting regioisomer, termed “8-<i>epi</i>-isoaplydactone”, could also be found in <i>A. dactylomela</i>