Abstract：
Tetrahydrobiopterin, one of the most crucial enzymatic cofactors acquired through biological synthesis and self-regeneration in the human body. During this process, it undergoes oxidation and deprotonation, forming quinonoid-dihydrobiopterin, which then tautomerizes to yield dihydrobiopterin. This study presents the thermodynamic and kinetic properties of each stage using theoretical calculations. Redox potentials and pKa values are determined using the Born-Haber cycle in implicit solvent models. Redox metabolites are characterized from calculated absorption spectra using time-dependent density functional theory. Rate constants for tautomerization steps are computed using Eyring\'s Transition State Theory, incorporating Wigner\'s tunneling correction. The N3 atom is identified as the most probable deprotonation site for H3B+. Spectral properties of intermediates are elucidated, highlighting key electronic transitions. Tautomerization steps occur through vibrational bending modes, and tunneling corrections significantly increase reaction rates. These findings provide a comprehensive understanding of the thermodynamics and kinetics of tetrahydrobiopterin regeneration, aiding in the modulation of its biological activity.
摘要：
四氢生物蝶呤,通过生物合成和人体自我再生获得的最关键的酶辅因子之一。在这个过程中,它经历氧化和去质子化，形成醌-二氢生物蝶呤，然后互变异构产生双氢生物蝶呤。本研究使用理论计算介绍了每个阶段的热力学和动力学性质。在隐式溶剂模型中使用Born-Haber循环确定氧化还原电位和pKa值。使用时间依赖性密度泛函理论从计算的吸收光谱表征氧化还原代谢物。互变异构步骤的速率常数是使用Eyring的过渡状态理论计算的，结合Wigner的隧道校正。N3原子被认为是H3B+最可能的去质子化位点。阐明了中间体的光谱特性，突出关键的电子转换。互变异构步骤通过振动弯曲模式发生，和隧道校正显着提高反应速率。这些发现为四氢生物蝶呤再生的热力学和动力学提供了全面的理解，帮助调节其生物活性。
