抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The photophysics and photochemistry of DNA is of great importance due to the potential damage of the genetic code by UV light. Quantum mechanical studies have played a key role in interpretating the results of modern time-resolved pump-probe spectroscopy, and in elucidating the main photoactivated reactive paths. This review provides a concise, complete picture of the computational studies carried out, approximately, in the past decade. We start with an overview of the photophysics of the nucleobases in the gas phase and in solution. We discuss the proposed mechanisms for ultrafast decay to the ground state, that involve conical intersections, consider the role of triplet states, and analyze how the solvent modulates the photophysics. Then we move to larger systems, from dinucleotides to single- and double-stranded oligonucleotides. We focus on the possible role of charge transfer and delocalized or excitonic states in the photophysics of these systems and discuss the main photochemical paths. We finish with an outlook on the current challenges in the field and future directions of research.

Quantum Mechanical Studies on the Photophysics and the Photochemistry of Nucleic Acids and Nucleobases

During the past decade the understanding of photo-induced ultrafast dynamics in molecular systems has improved at an unforeseen speed and a wealth of detailed insight into the fundamental processes has been obtained.This review summarizes our present knowledge on ultrafast dynamics in isolated molecules and molecular clusters evolving after excitation with femtosecond pulses as studied by pump–probe analysis in real time. Experimental tools and methods as well as theoretical models are described which have been developed to glean information on primary, ultrafast processes in photophysics, photochemistry and photobiology. The relevant processes are explained by way of example—from wave packet dynamics in systems with a few atoms all the way to internal conversion via conical intersections in bio-chromophores. A systematic overview on characteristic systems follows, starting with diatomic and including larger organic molecules as well as various types of molecular clusters, such as micro-solvated chromophore molecules. For conciseness the focus is on molecular systems which remain unperturbed by the laser pulses—apart from the excitation and detection processes as such. Thus, only some aspects of controlling and manipulating molecular reactions by shaped and/or very intense laser pulses are discussed briefly for particularly instructive examples, illustrating the perspectives of this prospering field.The material presented in this review comprises some prototypical examples from earlier pioneering work but emphasizes studies from recent years and covers the most important and latest developments until January 2006.

https://iopscience.iop.org/article/10.1088/0034-4885/69/6/R06/pdf

Ultrafast dynamics in isolated molecules and molecular clusters

Biochemical reactions are subject to the particular environmental conditions of planet earth, including solar irradiation. How DNA responds to radiation is relevant to human health because radiation damage can affect genetic propagation and lead to cancer and is also important for our understanding of how life on earth developed. A reductionist approach to unravelling the detailed photochemistry seeks to establish intrinsic properties of individual DNA building blocks, followed by extrapolation to larger systems, to incorporate interactions between the building blocks and the role of the biomolecular environment. Advances in both experimental and computational techniques have lead to increasingly detailed insights in the excited state dynamics of DNA bases in isolation as well as the role of the solvent and intermolecular interactions. This review seeks to summarise current findings and understanding.

Excited state dynamics of DNA bases

The decay paths on the singlet excited-state surface of 9H-adenine and the associated energy barriers have been calculated at the CAS−PT2//CASSCF level. There are three fundamental paths for the photophysics:  two paths for the 1Lb state which are virtually barrierless at the present level of theory and correspond to formation of the (n,π*) intermediate and direct decay to the ground state and a third path for ground-state decay of the (n,π*) state with an activation barrier of approximately 0.1 eV. The 1La state, which has the largest oscillator strength, either decays directly to the ground state or contributes indirectly to the excited-state lifetime by populating the two other states. The results are used to interpret the photophysics in terms of an excited-state plateau for the 1Lb state that corresponds to the short-lived excited-state component (approximately 0.1 ps) and a well (i.e., a proper minimum) for the (n,π*) state that gives rise to the long component (1 ps or more). The direct decay to th...

/pdf/excited-state-potential-energy-surface-for-the-photophysics-5g01xzcfjk.pdf

Excited-State Potential Energy Surface for the Photophysics of Adenine

Ab initio calculations and time-resolved photoionization spectroscopy were carried out to characterize the role of the lowest two pi sigma* excited states for the photoinduced processes in the adenine monomer, adenine dimer, and adenine-water clusters. The calculations show--with respect to the monomer--a stabilization of 0.11-0.14 eV for the pi sigma* states in different isomers of adenine dimer and an even bigger stabilization of 0.14-0.36 eV for isomers of adenine-(H2O)1 and adenine-(H2O)3. Hence, the stabilized pi sigma* states should play an important role in the excited-state relaxation of partially or fully solvated adenine. This conclusion is supported by experimental results: In the adenine monomer, strong n pi* state signals are observed. Those signals are reduced in adenine dimer and vanish in water clusters due to the competing relaxation via the pi sigma* states.

Relevance of πσ* states in the photoinduced processes of adenine, adenine dimer, and adenine–water complexes

Femtosecond pump-probe spectroscopy was combined with photoelectron-photoion coincidence detection to investigate the electronic structure and dynamics of isolated adenine (A) and thymine (T) dimers and the adenine-thymine (AT) base pair. The photoelectron spectra show that pipi* and npi* states are only weakly perturbed in the hydrogen-bound dimers as compared to the monomers. For cationic base pairs with internal energies greater than 1 eV, we observed considerable cluster fragmentation into protonated monomers. This process selectively removed signals from the npi* --> n-1 ionization channel in all dimers. The photoelectron spectra are compared to time-resolved mass spectra and confirm the assignment of short-lived pipi* and npi* populations in the adenine, thymine, and mixed AT dimers.

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Electronic Structure of Adenine and Thymine Base Pairs Studied by Femtosecond Electron-Ion Coincidence Spectroscopy

We present femtosecond pump–probe mass and photoelectron spectra for adenine (A) and microhydrated Am(H2O)n clusters. Three distinct relaxation processes of photoexcited electronic states were distinguished: in unhydrated A, relaxation of the optically bright ππ* state occurred via the dark nπ* state with respective lifetimes of <0.1 and 1.3 ps. In microhydrated clusters A(H2O)n, relaxation via the nπ* state is quenched by a faster relaxation process, probably involving πσ* states. For the predominantly hydrogen-bonded adenine dimer (A2), excited state relaxation is dominated by monomer-like processes. When the adenine dimer is clustered with several water molecules, we observe a nanosecond lifetime from excimer states in π-stacked clusters. From the electron spectra we estimate adiabatic ionization potentials of 8.32 eV (A), 8.27 eV (A(H2O)1), 8.19 eV (A(H2O)2), 8.10 eV (A(H2O)3), 8.18 eV (A2), and 8.0 eV (A2(H2O)3–5).

Excimer states in microhydrated adenine clusters

Fast excited-state relaxation in H-bonded aminopyridine clusters occurs via hydrogen transfer in the excited state. We used femtosecond pump-probe spectroscopy to characterize the excited-state reaction coordinate. Considerable isotope effects for partially deuterated clusters indicate that H-transfer is the rate-limiting step and validate ab initio calculations in the literature. A nonmonotonous dependence on the excitation energy, however, disagrees with the picture of a simple barrier along the reaction coordinate. An aminopyridine dimer serves as a model for Watson-Crick base pairs, where similar reactions have been predicted by theory.

Ultrafast deactivation processes in aminopyridine clusters: excitation energy dependence and isotope effects.

The genetic information of all living organisms on the earth is encoded in DNA, and the DNA bases form the characters carrying this information. To ensure survival in harsh conditions, DNA and its building blocks must be quite robust against degradation or chemical modification. This chapter provides an understanding of the stability of DNA against photochemical damage arising from irradiation with ultraviolet light. It investigates small building blocks of DNA to obtain a detailed understanding of photochemical and photophysical processes, which may allow a bottom–up description of the photochemical properties of DNA. Recent advances investigating base pairs and microhydrated clusters composed of the bases adenine and thymine are presented. For the investigations, time-resolved excitation-ionization spectroscopy with 1 kHz ∼100 femtosecond pulses in the ultraviolet for photoexcitation and 400 or 800 nm pulses for multiphoton ionization was used.

V. R. Smith

Papers

Relevance of πσ* states in the photoinduced processes of adenine, adenine dimer, and adenine–water complexes

Electronic Structure of Adenine and Thymine Base Pairs Studied by Femtosecond Electron-Ion Coincidence Spectroscopy

Excimer states in microhydrated adenine clusters

Ultrafast deactivation processes in aminopyridine clusters: excitation energy dependence and isotope effects.

Photochemistry and Dynamics of Base Pairs