Note of Introduction to Bioorganic Chemistry and Chemical Biology: Part 1 (《化學生物學》讀書筆記：第一部分)

Chapter 1: The Fundamentals of Chemical Biology (第 1 章 化學生物學基礎)

1.0 INTRODUCTION (引子)

1.0.1 Why organize a book on chemical biology around biooligomers? (為什么要圍繞生物大分子來撰寫一本關于化學生物學的書)

In a view of subject concept:

• Chemistry offers insight into the behavior of molecules. (For its subdiscipline, doing so with a limited range)
• Organic chemistry compromises between qualitative and quantitative approach, capable of explaining the molecular diversity for evolution of organisms.
• Chemical biology applies the rules of chemistry to biological systems.

從學科思想的角度來看：

• 化學是研究分子行為的學科，（化學的分支學科則在特定范圍內研究）
• 有機化學平衡定性與定量方法，可用于解釋生物進化所需的分子多樣性，
• 化學生物學將化學規則應用于生物系統，

p.s. "Compromise" here manifests a certain degree of equilibrium, which contains both strict quantum chemistry and empirical laws, for me. Later it would be expanded in Chapter 2.

注：我認為這里原文的“compromise”體現了有機化學在嚴謹的量子化學和經驗規律之間的平衡（譯文“一種特有的定性和定量方法”翻譯的并不甚好），本書第二章對此有具體說明，

Combinatorial assembly strategy

• means to modularly assemble a diverse population from limited subunits.
• could be appreciated in the "letter => word => sentence => paragraph" organization of writing.
• generates diverse populations at different levels of living system.

組合策略

• 指以有限單元模塊化組裝成多樣高級單元的程序，
• 可在“字母 => 單詞 => 句子 => 段落”的英文寫作組織中體現，
• 在生命系統的不同層次產生多樣化的群體，

The central dogma of molecular biology

• governs the assembly of biooligomers.
• is the thematic organization for this book.

分子生物學的中心法則

• 控制著生物分子的組裝，
• 是本書撰寫的主線，

p.s. Back to my high school days, my biology teacher highlighted central dogma as the flow of genetic information. Here, the diversity behind evolution weighs strongly with the authors, for which the importance of "flow" appears as the government of biooligomer assembly. (The author also used "biooligomer" rather than common "biomolecule" to underscore the significance of "assembly")

注：我高中的生物老師就常常強調中心法則表明了遺傳資訊的流向，本書的作者把驅動生物進化的多樣性作為化學生物學核心思想之一，在這種認識上中心法則的流向也是生物分子組裝的決定方向，我們同時也注意到本書作者表達“生物分子”常用的是“biooligomer”一詞（直譯為“生物聚合物”），其強調“組裝”之意不言自明，

1.2 GENES (基因)

1.2.1 A gene is made up of a promoter and a transcribed sequence (基因由啟動子和轉錄序列組成)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

A gene

• contains a transcription-factors-binding promoter and a RNA-encoding DNA sequence.
• is often organized into an operon or cluster of genes with other genes which are functionally related and controlled by the same promoter. (McC operon in E. coli as an example)

一個基因

• 包含能結合轉錄因子的啟動子序列和能編碼 RNA 的一段 DNA 序列，
• 常常和其它功能相關的基因被整合在同一個操縱子（或基因簇）中，這些基因具有相同的啟動子，（如大腸桿菌中的 McC 操縱子）

p.s. Latent translation mistake: the original text says "the control of a common DNA promoter sequence", where "common" obviously means "shared" rather than "usual".

注：此處可能有翻譯錯誤，原文說“the control of a common DNA promoter sequence”，這個“common”顯然指的是“共同的”，而非“常見的”，

1.3 GENOMES (基因組)

1.3.1 We have sequenced the human genome and many others. Now what? (我們已經對人類基因組和許多其他基因組進行了測序，現在該做什么？)

The gap between sequencing protein and understanding its function is from

• the difficulty for studying related non-protein biooligomers.
• the lack of certain conditions for protein of interest to function in experiment.
• the lack of complete dynamic system in experiment.

了解蛋白質序列和理解蛋白質功能相差甚遠，這是因為

• 許多蛋白質的功能和不易研究的生物分子有關，
• 許多蛋白質只能在一些特定條件下發揮相關功能，
• 許多蛋白質只有在動態的整體中才能發揮功能，

1.3.2 We are far from understanding cells that we understand the best—Escherichia coli (我們還遠不了解我們認為最了解的大腸桿菌)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

E. coli

• has numerous strains, with the common laboratory strain being E. coli K-12.
• is typically a little more than 1 μm in diameter.
• has a complex coating composed of two fluid lipid membranes and a sandwiched tough, web-like cell wall in the periplasm.
• could fission into cooperative colonies with chemical signaling under nutrient-rich conditions.
• could exchange genetic material with other strains with thin hair-like projections on its surface.

大腸桿菌

• 存在多種菌株，其中實驗室常見的是 K-12 菌株，
• 直徑通常略大于 1 μm，
• 的外壁是雙層膜結構，堅韌網狀的細胞壁存在于兩層膜間的周質間隙中，
• 在營養豐富的條件下可以分裂形成生產合作的菌落，菌落內部存在著化學信號，
• 可以通過表面的發狀突起和其他菌株交換遺傳物質，

p.s. The mentioned "hair-like projections" might be the conjugative pilus. A illustration is attached below for explantion.

注：這里說的“發狀突起”指的可能是接合菌毛，下方的插圖圖注中有進一步說明，

1.3.4 You cannot judge a cell by its genome (我們不能僅通過基因組來判定一個細胞)

In a view of genome similarity:

• Strains of E. coli have very different genomes.
• Mammals (such as mice and humans) share 99% of the same genes.
• All humans of the same sex are 99.9% identical.

從基因組相似度的角度看：

• 大腸桿菌不同菌株基因組差異很大，
• 哺乳動物（如老鼠和人類）中同源基因的比例高達 99%，
• 同性別人類的基因組 99.9% 是相同的，

p.s. Latent translation mistake: The original text goes that "Strains of E. coli have similar structures but very different genomes, whereas the opposite is true for mammals such as mice and humans, which share 99% of the same genes." It is hard to tell the exact meaning of "the opposite", is it an intraspecie sequence similarity or an interspecie gene homology? A reliable clear description from Lewin's Gene Ⅻ says "human and chimpanzee genomes shares 98.5% sequence similarity", which makes me correct the translation into gene homology.

注：此處可能有翻譯錯誤，原文說“Strains of E. coli have similar structures but very different genomes, whereas the opposite is true for mammals such as mice and humans, which share 99% of the same genes.”，這里并不好直接讀出“99%”指的是種類序列相似性還是種間基因同源性，我參看了《基因Ⅻ》，其中提到人類和黑猩猩的序列相似度就能達到 98.5%，我因而認為 99%值的更可能是基因同源性，

1.4 SOURCES OF DIVERSITY BEYOND GENOMES (基因組以外的生物多樣性來源)

1.4.2 RNA splicing amplifies the diversity of the transcriptome (RNA 剪接增加了轉錄組的多樣性)

Splicing

• cannot be predicted from DNA sequence.
• depends on environmental conditions.

剪接

• 位點仍無法由 DNA 序列預測得到，
• 同時取決于環境條件，

1.4.3 Post-translational modification of proteins amplifies the diversity of the proteome (蛋白質的翻譯后修飾增加了蛋白質組的多樣性)

Post-translational modifications include:

• trimming
• splicing
• phosphorylation
• glycosylation
• oxidation
• addition of membrane anchors
• fusion with other proteins
• alkylation
• acetylation, etc.

蛋白質翻譯后修飾包括：

• 修剪
• 剪接
• 磷酸化
• 糖基化
• 訊訓
• 添加膜錨定標簽
• 與其他蛋白融合
• 烷基化
• 乙酰化等

1.4.4 Beyond template-directed synthesis of biooligomers (非模板導向的生物分子的合成)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

Enzymes synthesize some biooligomers without biooligomer template,

• which are polyketides, oligosaccharides, and terpenes.
• where the enzyme-encoding genes are mostly randomly ordered in genome, with exceptions of some important polyketide synthases.

有些生物分子的酶催化合成不需要以其他生物分子作為模板，

• 如聚酮、糖類和萜類化合物，
• 編碼有關酶的基因在基因組中常常任意排列，一些重要的聚酮合成酶基因除外，

Further modification could be done on polyketides, oligosaccharides, and terpenes,

• such as cyclization, oxidation, reduction, and cleavage.
• which may mask the initial structure.

聚酮、糖類和萜類化合物在合成后也可被進一步修飾，

• 如環化、訊訓、還原和裂解，
• 這些修飾會使最終產物的結構大不相同，

1.5 COMBINATORIAL ASSEMBLY GENERATES DIVERSITY (組裝產生的多樣性)

1.5.4 The human immune system uses combinatorial biosynthesis (人類免疫系統使用組合生物合成策略)

The diversity of antibody is from

• varible (V)-diversity (D)-joining (J) module library combination for light chain-heavy chain pair.
• imprecise joining of genetic modules.
• hypermutation in V, D and J modules in B lymphocytes.

抗體的多樣性源于

• 以可變區，差異區和連接區模塊文庫的組合策略產生輕重鏈組合，
• 以不精確的方式連接基因模塊，
• B 淋巴細胞中 V、D、J 區的高突變頻率，

1.6 SOME COMMON TOOLS OF CHEMICAL BIOLOGY (一些常見的化學生物學工具)

1.6.3 Powerful microbiological screens reveal interesting chemical phenomena (強大的微生物篩選揭示了有趣的化學現象)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

Bacterial selection

• is ideal for assay of extremely high throughput.
• may fail due to the resilience of bacteria population from natural mutation.

細菌選擇

• 可以應用于極高通量分析場景，
• 可能因為細菌種群的自然突變而無效，

1.6.4 Viruses deliver genes efficiently (病毒高效地傳遞基因)

Importance of viruses in molecular biology:

• Viral gene delivery is the only non-disruptive method for gene delivering.
• In order to overwhelm the host enzymes, viral enzymes are commonly superior in efficiency.
• Viruses are lean and simple.

病毒在分子生物學中的重要性：

• 病毒是唯一的非破壞性基因遞送方法，
• 為了“接管細胞”，病毒編碼的酶往往更加高效并適合作為工具酶，
• 病毒既精密又簡單，

1.6.5 Vast libraries of proteins can be screened in vitro using bacteriophages (可以使用噬菌體在體外篩選大量的蛋白質文庫)

Phage display technique

• used engineered recognition protein on phage surface to screen ligand-binding protein.
• uses phage infection to re-establish a population of clones.

噬菌體展示技術

• 利用在噬菌體表面展示目標蛋白進行分子識別蛋白的篩選，
• 利用噬菌體感染細菌來重建克隆群體，

p.s. Latent translation mistake: The original text says "for the ability to cling to a surface" rather than "cling to a protein".

注：此處可能有翻譯錯誤，原文說“for the ability to cling to a surface”，而非“cling to a protein”，翻譯成“對目標蛋白的結合能力”并不合適，

1.6.8 Short RNA molecules silence gene expression (短鏈 RNA 分子沉默基因表達)

Advantages of RNA interference:

• Short synthetic RNA can enter human cells.
• Design and synthesis of short RNA are much easier than those of small molecules.

RNA 干擾技術的優勢：

• 短鏈 RNA 分子可以穿過細胞膜進入人類細胞，
• 相較于小分子，短鏈 DNA 的設計和合成更為便捷，

Obstacles for RNA interference:

• The process of RNA cell entry in poorly understood. (Injection delivery fails for non-eye organs)
• Potential off-target effect.
• RNA interference can only affect protein translation rather than translated protein.

RNA 干擾技術發展的制約：

• 人們對 RNA 進入細胞的程序知之甚少，（注射遞送僅對眼睛有效）
• 潛在的脫靶效應不易評估，
• RNA 干擾只能阻止蛋白質產生，而無法影響已經成熟的蛋白質，

1.6.11 Model organisms teach us about humans (模式生物教給我們關于人類的知識)

p.s. Latent translation mistake: A more well-acknowledged translation of "model organism" exists.

注：此處可能有翻譯錯誤，“model organism”更常見的翻譯顯然是“模式生物”而非“生物模型”，

Why we study microscopic soil worms and fruit flies?

• As a consequence of evolution, worms, flies, and humans share similar genes, similar proteins, and similar biochemical mechanisms.
• C. elegans is transparent, allowing one to see the cells and the organs in developmental biology study.
• D. melanogaster has more human-like stages of embryological development.

為什么我們要研究土壤蠕蟲和果蠅：

• 從進化的角度看，蠕蟲、蒼蠅和人類共享相似的基因、蛋白質和生化機制，
• 秀麗隱桿線蟲是透明的，這使得發育生物學家可以直接觀察其內部的細胞和器官，
• 黑腹果蠅胚胎發展的階段更接近人類，

Chapter 2: The Chemical Origins of Biology (第 2 章 生物體的化學起源)

2.0 INTRODUCTION (引子)

2.0.0 Introduction (引子)

Erwin Schr?dinger's arguement in What is life：

• All living things are governed by the same physical laws as those encountered in everyday life.

Erwin Schr?dinger 在《生命是什么》中提出重要論斷：

• 所有生物體系都遵循著與我們日常生活中所遇到的相同的物理學定律，

2.1 MECHANISTIC ARROW-PUSHING IS AN EXPRESSION OF MOLECULAR ORBITAL THEORY (電子轉移機理是分子軌道理論的一種表達形式)

2.1.1 Three properties control chemical reactivity (三大性質控制化學反應性)

Arrow-pushing

• was first introduced by Robert Robinson and Arthur Lapworth in 1922. (Before quantum mechanics)
• needs us to choose curved arrow sets according to the energy of transition state.

箭推機理

• 由 Robert Robinson 和 Arthur Lapworth 在 1922 年首次使用，
• 的書寫主要取決于對應歷程的過渡態能量，

p.s. Here, I choose to translate it by myself to convey both "arrow in form" and "mechanism behind". To be honest, the original narrative is quite interesting but personal. A better logic chain would be "using arrowing-pushing to present mechanism and choosing mechanism by its transition state energy".

注：這里我嘗試自己翻譯了一下，我認為“箭推機理”這個表述既照顧了箭頭的形式又包括了機理的內涵，其實作者在這個部分的敘述是較為個人化的，盡管十分有趣，但我認為更好的說法可能是“依據過渡態能量判斷一種機理的可行性，并用箭頭恰當的表現”，

A basic three-term equation to quantify the energy of transition state could be

• \(\mathrm{Energy} \quad \propto \mathrm{Charge \, Interactions} \quad + \mathrm{(Non \mbox{-} charge) \, Repulsive \, Interactions} \quad - \mathrm{(Non \mbox{-} charge) \, Attractive \, Interactions}\)

反應過渡態的能量可以分為三部分，由下式進行估算

• \(\mathrm{能量} \quad \propto \mathrm{電荷相互作用} \quad + \mathrm{（非電荷）排斥作用} \quad - \mathrm{（非電荷）吸引作用}\)

p.s. I was pretty perplexed the first time I saw this equation and had two question: 1) When we are talking about charge interaction it could be repulsive or attractive, so why "repulsive" again in the second term? 2) Let's say the last two terms are "non-charge interaction", then the equation is quite a rubbish. However, it worth to be presented in this way regarding later expansion and I add "non-charge" here. By the way, the mathematical signs here are obscure as well. It might means "Basing on the consideration of charge interactions, non-charge repulsive interactions increase it and non-charge attractive interactions decrease it".

注：其實我第一次看這部分的時候完全沒有理解，當時產生了兩個疑問：其一是電荷作用有正有負，為什么后兩項還在說“吸引”和“排斥”；其二是就算后兩項是默認非電荷作用，那這個式子也是廢話一句，當然，我看到下文的擴展后才理解了作者這樣寫的意圖，此外，作者這里用了十分晦澀的數學符號，我認為他可能是想表達“我們首先可以基于電荷相互作用得到一個過渡態能量，在此基礎上，額外的非電荷排斥作用使能量升高，而非電荷吸引作用使能量降低”這樣一個意思，

2.1.2 Perturbational molecular orbital theory connects arrow-pushing with quantum mechanics (微擾分子軌道理論將箭推機理與量子力學聯系在一起)

Ian Fleming developed the equation vide supra into a qualitative expression of perturbational molecular orbital theory

• \(\mathrm{Reaction \, Energy} \quad \propto \mathrm{Coulomb's \, Law} \quad + \mathrm{Sterics} \quad - \mathrm{Filled \mbox{-} unfilled \, Orbital \, Overlap}\)

Ian Fleming 通過定性表達微擾分子軌道理論發展了對過渡態能量的比較方法

• \(\mathrm{反應能量} \quad \propto \mathrm{庫侖定律} \quad + \mathrm{空間效應} \quad - \mathrm{填充軌道與未填充軌道的重疊}\)

About the equation of I. Fleming:

• Sterics is actually from the overlap of filled orbitals.
• Filled-unfilled orbital overlap alone is the underpinning of arrow-pushing.

關于 I. Fleming 的擴展式

• 空間效應產生于填充軌道之間的相互排斥，
• 填充軌道與非填充軌道的重疊才是箭推機理的根本，

2.1.3 Six canonical frontier orbitals can be used to predict reactivity (六大經典分子軌道用來預測化學反應性)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

p.s. Latent translation mistake: "canonical" here could be regarded as a advance "classical".

注：此處可能有翻譯錯誤，這里“canonical”這個詞指的其實就是“經典的”之意，

In a view of (hybrid) atomic orbitals:

• p orbital has higher energy than s orbital.
• sp³ hybrid orbital has higher p character and higher energy.
• Basicity of carbanions could be explained in this way.

從（雜化）原子軌道的角度看：

• p 軌道相比 s 軌道能量更高，
• sp³ 雜化軌道的 p 成分更高，因此能量更高，
• 我們可以解釋不同碳負離子的堿性差別，

In a view of frontier molecular orbitals:

• Six canonical types of frontier molecular orbitals in order of energy from low to high are: σ, π, nonbonded lone pairs (n), empty p orbitals, π^* and σ^*.
• Energy order of filled frontier orbitals could be explanation of nucleophilicity.
• Energy order of unfilled frontier orbitals could be explanation of electrophilicity.

從前線分子軌道的角度看：

• 六種經典前線分子軌道按照能量從低到高排序為：σ、π、非鍵孤對電子 n、p 空軌道, π^* 和 σ^*，
• 填充的前線分子軌道的能量順序可以用于解釋物種親核性，
• 未填充的前線分子軌道的能量順序可以用于解釋物種親電性，

2.1.4 Electronegativity affects both frontier orbitals and Coulombic interactions (電負性影響了前線軌道和庫侖相互作用)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

Electronegativity affects reactivity in a complex manner:

• Atom of high electronegativity lowers the energy of all orbitals.
• Partial charge from electronegativity also affects Coulombic interactions.

電負性對反應活性有著雙重影響：

• 高電負性的原子將會使所有軌道的能量降低，
• 電負性通過影響部分電荷影響庫侖相互作用，

Two broad generalizations will cover most of the biochemical reactions:

• Focus on the decrease of orbital energy when a nucleophile attacks on carbon atoms.
• Focus on the increase of negative charge when a nucleophile attacks on cations.

對于大多數生化反應可以參照以下兩條普適性結論進行判斷：

• 對親核試劑進攻碳原子的反應，我們應該關注高電負性原子的前線軌道能量更低，
• 對親核試劑進攻質子或正離子的反應，我們應該關注高電負性原子攜帶更多的負電荷這一事實，

2.1.5 Curved mechanistic arrows depict the interaction of filled orbitals with unfilled orbitals (彎曲的反應機理箭頭描繪填充軌道與未填充軌道的相互作用)

Arrow-pushing mechanisms

• are more art than science.

箭推機理的書寫

• 更像是一門藝術而非科學，

Curly arrows

• according to I. Fleming, "illustrate the electron distribution in the frontier orbital".
• depict the interaction of filled orbitals with unfilled orbitals.

彎曲箭頭

• 在 I. Fleming 看來“描繪了前線軌道的電子分布”，
• 描述的是填充軌道和未填充軌道的相互作用，

2.1.6 There are three basic rules for mechanistic arrow-pushing (箭推機理書寫的三大基本規則)

Rules for arrow-pushing:

• Arrows never start with atoms.
• Arrows never start or end on charges.
• Arrows begin with lone pairs, π bonds, or σ bonds, and end on unfilled orbitals.

箭推機理書寫規則：

• 箭頭不從原子出發，
• 箭頭不從電荷出發，也不結束于某個電荷，
• 箭頭起始于孤對電子、π 鍵或 σ 鍵，終止于未填充軌道，

2.2 HYDROGEN BONDS AND PROTON TRANSFERS (氫鍵和質子轉移)

2.2.1 Hydrogen bonds involve three atoms (氫鍵涉及三個原子)

Hydrogen bonds are

• mainly a Coulombic interaction.
• sensitive to the polarity of the environment. (Weak in high dielectric water, otherwise in lipid membrane or interior of protein)
• commonly slightly less than 2 ?.

氫鍵

• 主要是庫侖相互作用，
• 強度對環境極性敏感，（高介電常數的水中氫鍵很弱，低介電常數的脂膜和蛋白質內部氫鍵很強）
• 通常略短于 2 ?，

Depicting mechanisms involving hydrogen bonds must

• either omit the arrow-pushing for the proton transfer step.
• or omit the formation of the obvious hydrogen bond.

為了正確描繪有氫鍵參與的機理

• 要么忽略質子轉移中的電子轉移，
• 要么忽略氫鍵，

2.2.2 Proton transfers to and from heteroatoms are usually very fast (雜原子上的質子轉移非常快)

Proton transfers

• are usually very fast to and from oxygen, nitrogen and even sulfur atom. (Except for carbon)
• are actually diffusion-controlled when strongly favorable. (10⁹ M^-1 s^-1)
• heavily rely on the hydrogen bonds.

質子轉移

• 在氧、氮甚至硫上發生的非常快，（除了碳上的質子）
• 較強時，其速率由水溶液擴散控制，（10⁹ M^-1 s^-1）
• 十分依賴于氫鍵，

2.2.3 Linear geometries are preferred for proton transfers (線性幾何構型是質子轉移的最優構型)

Most intramolecular proton transfers

• are actually faster to be done in two steps with the help of protonic acid in medium.

大多數分子內質子轉移反應

• 借助環境中的質子酸分兩步完成會更加高效，

2.3 PREBIOTIC CHEMISTRY (前生命化學)

2.3.1 HCN and CH₂O are key ingredients in the primordial soup (HCN 和 CH₂O 是原始湯的主要成分)

Prebiotic chemistry

• attempts to understand and re-create the chemical origin of life.

前生命化學

• 試圖解釋和重塑生命起源，

Molecular ingredients of life

• could be studied by spectroscopy of interstellar space.
• include water, ammonia, hydrogen cyanide, acetonitrile, acrylonitrile, cyanogen (NC–CN), and cyanoacetylene.

生命的化學原料

• 可以通過宇宙空間的光譜進行研究，
• 包括水、氨氣、氰化氫、乙腈、丙烯腈、氰（NC-CN）、丙炔腈等，

From these ingredients:

• Ribose is pentamer of formaldehyde.
• Adenine is pentamer of hydrocyanic acid.

基于上述原料：

• 核糖是甲醛的五聚體，
• 腺嘌呤是氫氰酸的五聚體，

In aqueous solution at room temperature, polymerization of hydrocyanic acid forms

• tetramer diaminomaleonitrile (DAMN).
• larger oligomer to hydrolyze into adenine.

在室溫下，氫氰酸水溶液可發生聚合，生成

• 四聚體二氨基馬來腈（DAMN），
• 更大的低聚物并水解生成腺嘌呤，

2.3.2 Solutions of HCN contain both nucleophile and electrophile at pH 9.2 (氫氰酸溶液在 pH = 9.2 下存在著親核體和親電體)

In a rigorous arrow-pushing mechanism:

• Each set of curved arrows corresponds to a single elementary reaction with one transition state.
• Most steps contain no more than two arrows.

在嚴格的箭推機理中：

• 每組彎曲箭頭對應著一個基元反應，具有一個過渡態，
• 絕大多數的反應步驟不會超過兩個箭頭，

2.3.3 HCN forms purines and pyrimidines under prebiotic conditions (HCN 在前生命化學條件下生成嘌呤和嘧啶)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

To generate purines:

• Ultraviolet radiation convert DAMN into aminoimidazole carbonitrile (AICN).
• AICN can react with HCN to form adenine, or with urea to form guanine.

關于嘌呤的產生：

• DAMN 在紫外輻射下會生成氨基咪唑腈（AICN），
• AICN 可以和 HCN 反應生成腺嘌呤，或是和尿素反應生成鳥嘌呤，

To generate pyrimidines:

• Cyanoacetylene can react with water to form cyanoacetaldehyde.
• Cyanoacetaldehyde then reacts with guanidine to form cytosine.
• Hydrolysis of cytosine would form uracil.

關于嘧啶的產生：

• 丙炔腈與水反應可以生成氰基乙醛，
• 氰基乙醛可以和胍縮合得到胞嘧啶，
• 胞嘧啶進一步可以水解生成尿嘧啶，

When writing arrow-pushing mechanisms,

• omiting some obvious steps by stacking elementary reaction arrows is acceptable.
• we should always leave out intermediate structures and the corresponding curved arrows. (Three-arrow rule)

在書寫箭推機理的時候，

• 可以通過堆疊基元反應箭頭省略掉一些顯而易見的步驟，
• 如果要省略中間體結構，必須同時省略彎曲箭頭，（三箭頭規則）

2.3.4 Aldol reactions with formaldehyde generate carbohydrates (甲醛的羥醛縮合反應可生成碳水化合物)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

Formose reaction

• generates all possible carbohydrates from formaldehyde and glycoaldehyde.
• is actually a series of aldol reaction.
• requires calcium for catalysis.

甲醛聚糖

• 利用甲醛和糖醛生成各種可能的碳水化合物，
• 實際上是一系列的羥醛縮合反應，
• 需要鈣離子催化，

2.3.5 Cyanide catalyzes the benzoin reaction (氰化物催化安息香縮合反應)

Glycoaldehyde

• was from cyanide-catalyzed benzoin reaction of formaldehyde.

糖醛

• 來源于氰離子催化的甲醛的安息香縮合反應，

2.3.7 Amino acids arise spontaneously under prebiotic conditions (氨基酸在前生命體條件下自發生成)

In famous Miller-Urey experiment:

• Mixture of methane, ammonia, hydrogen and water vapor mocked primordial atmosphere.
• Electrical discharge mocked lighting.
• Several amino acids were found as products.
• Classical Strecker reaction might take place.

在著名的 Miller-Urey 實驗中：

• 甲烷、氨氣、氫氣和水蒸氣的混合物被用于模擬原始大氣，
• 以放電模擬閃電現象，
• 產生了若干種天然氨基酸，
• 可能發生了著名的 Strecker 反應，

2.4 NONBONDING INTERACTIONS (非鍵相互作用)

2.4.1 Essentially everything taking place in the cell involves nonbonding interactions (本質上，細胞中發生的一切都涉及非鍵相互作用)

Nonbonding forces are

• sometimes "strong", regarding the hydrolyzable, thermodynamically weak covalent bonds in biooligomers.
• kinetically labile.

非鍵相互作用

• 相較于生物分子可水解的共價鍵在熱力學上甚至更加穩定，
• 具有動力學上的易變性，

p.s. Latent translation mistake: the original text says "the covalent bonds that link the subunits of biooligomers are also thermodynamically weak relative to hydrolysis", where "relative" probably means "relevant" rather than "opposite".

注：此處可能有翻譯錯誤，原文說“the covalent bonds that link the subunits of biooligomers are also thermodynamically weak relative to hydrolysis”，這個“relative”我認為指的是“相關的”，而非“相較于”，

2.4.3 For nonbonding interactions, the energies can be fitted to a simplified equation (對于非鍵相互作用，能量可以轉換成一個簡化的方程)

Formal charges from Lewis structure

• are often opposite to the actual partial charge.
• could present the net effect of all Coulombic interactions based on partial charges.

Lewis 電子式標注的形式電荷

• 常常和實際的部分電荷相反，
• 可以表達所有部分電荷庫侖相互作用的凈效應，

2.4.5 It is helpful to distinguish reversible from irreversible interactions (區分可逆與不可逆的相互作用是非常有益的)

Aromatic rings can interact

• with each other either in parallel or in T-shaped structure, giving out roughly equivalent strengths.
• in an offset orientation in order to position regions of electron density over comparatively electron-deficient center of another ring.
• with cations, C-H and the lone pairs of oxygens.

芳環可以

• 以平行或 T 形的方式相互作用，這兩種方式的作用強度相近，
• 在作用時發生一定錯位以讓一個環的富電子區域和另一個環的貧電子中心相互接近，
• 與陽離子、C-H 鍵和氧原子上的孤對電子相作用，

p.s. For readers interested in π-π stacking interaction, I strongly recommend Angew. Chem. Int. Ed. 2008, 47, 3430–3434 from bigshot in quantum chemistry Prof. Dr Stefan Grimme. Latent translation mistake: the original text says "the arenes prefer an offset or displaced orientation", where "displaced" obviously means "offset" rather than "delocalized".

注：若讀者對 π-π 堆疊相互作用感興趣，我強烈推薦量子化學大牛 Stefan Grimme 教授的 Angew. Chem. Int. Ed. 2008, 47, 3430–3434，同時，此處可能有翻譯錯誤，原文說“the arenes prefer an offset or displaced orientation”，這個“displaced”顯然指的是“錯位的”，而非“離域的”，

Aqueous environment matters, because

• its high bulk dielectric constant screens charges, destabilizing salt bridge.
• water molecules can form hydrogen bonds to compete with other interactive candidates.

水環境十分重要

• 一方面因為高介電常數的水可以屏蔽電荷，使鹽橋作用大幅削弱，
• 另一方面水分子可以形成氫鍵，和其他物種競爭相互作用，

2.4.6 Entropy makes it difficult to identify favorable states among seemingly endless possibilities (熵使我們很難在看似無窮無盡的可能性中確定有利的狀態)

In order to use nonbonding forces to study biological problems without being trapped by effect of entropy,

• we should alway contrast systems with similar configurations.

為了不受熵驅動優勢的影響研究涉及非鍵力的生物問題，

• 我們應當總是比較處于相似構象或構型下的狀態，

2.4.7 The hydrophobic effect results from a balance between attractive forces and entropy (疏水效應是由吸引力和熵之間的平衡引起的)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

Comparing hydrogen bonds and dispersive interactions:

• Hydrogen bonds are directional, incurring a high entropic cost.
• Dispersive can easily sum up without a large entropic penalty.

比較氫鍵和色散作用：

• 氫鍵是定向的，因此氫鍵形成往往伴隨著很大的熵減，
• 色散作用并沒有強烈的取向定向，它們很容易相互疊加而不造成顯著的熵減，

2.5 THE POWER OF MODULAR DESIGN (模塊化設計的魅力)

2.5.0 Introduction (引子)

Modular design

• reduces the number of molecular parts for structure construction, simplifying the energy-intensive operations.

模塊化設計

• 減少了構建細胞結構的分子部件的數量，進而簡化了相關的能源密集型操作，

2.5.2 Lability correlates inversely with information longevity (可變性與資訊壽命成反比)

p.s. Latent translation mistake: A previously mentioned translation of "lability" exists.

注：此處可能有翻譯錯誤，“lability”在前文中翻譯為“可變性”而非“顯然更好”，

A molecule with more robust backbone functional groups

• has more longevity and less lability.
• is better as information carrier.
• has less copies in cell.

由更穩定的官能團構成骨架的分子

• 壽命更長，可變性更弱，
• 可更好地作為資訊載體，
• 往往在細胞中拷貝更少，

2.5.3 Why are esters more reactive than amides? (為什么酯的反應活性比酰胺強？)

Nitrogen lone pairs are more nucleophilic than oxygen lone pairs,

• making it more likely to donate into carbonyl through resonance in amides.

氮的孤對電子較氧上的親核性更強，

• 因此孤對電子通過共振作用對羰基的貢獻在酰胺中更容易發生，

2.5.4 Why are phosphate esters less reactive than carboxylic esters? (為什么磷酸酯的反應活性不如羧酸酯？)

p.s. Here, the content structure is personally reorganized for conciseness.

注：出于簡明考慮，本小節的內容結構有所調整，

For phosphate esters,

• 3p orbital of phosphorus is unlikely to effectively overlap with 2p of oxygen.
• four oxygen with high negative charge on phosphorus tend to repel nucleophiles. (That's why Mg²⁺ is necessary for phosphodiester hydrolysis)

對于磷酸酯

• 磷的 3p 軌道無法和氧原子的 2p 軌道高效重疊，
• 四個帶負電荷的磷原子會強排斥親核試劑，（所以水解磷酸二酯的酶總是鎂離子依賴的）

In the case of pyramidal molecule inversion:

• sp³ center atom undergoes sp² transition state.
• inverting atom takes s character from axial lone pair for equatorial bonds.
• equatorial electronegative substituents might inhibit such process.

在三角錐分子翻轉的情景中：

• 中心原子經歷了 sp³ => sp² 的過渡態轉變，
• 中心原子從軸向孤對電子那里獲取 s 成分并將其應用于平伏鍵，
• 若平伏鍵有強電負性取代基，翻轉程序將被抑制，

p.s. The author also emphasize the unfavorable contribution of oxygens to the transition state of phosphate ester. It is, however, obviously a minor factor regarding the strong screening effect of negative charged oxygens. And I choose not to underscore it as the author did here. Readers could resort to the original text for more information.

注：此處作者在原文中也強調了磷酸酯上氧原子作為“平伏鍵強電負性取代基”對過渡態的影響，但我認為這相較于負電荷氧原子對親核試劑的直接屏蔽顯然是次要因素，因此也未多在此論述，感興趣的讀者可自行參閱原文，

Acknowledgements (致謝)

I sincerely thanks Prof. Dr Shi Kuang from Hunan University for her generous help and contribution to the section vide infra:

• Section 2.5.4

M. Zheng-Bing Gao from Wuhan No.3 Middle school for her generous help and contribution to the section vide infra:

• Section 1.0.1

And I thanks M. Zhi-Ming Xing from Hunan University for his contribution to the section vide infra:

• Section 2.5.4

我由衷感謝湖南大學曠實教授對以下小節的慷慨幫助：

• 2.5.4 小節

武漢三中高正兵老師對以下條目的慷慨幫助：

• 1.0.1 小節

此外，我感謝湖南大學邢致明先生對以下小節的貢獻：

• 2.5.4 小節

Portal to Catalog of More Notes （鏈接：學科學習筆記目錄）

Portal: here （點左側鏈接直達頁面）

by Syl & Sylvia @ 2023-06-26 00:06:15 @ Changsha, Yuelu District
originally post @ https://www.cnblogs.com @ 2023-06-26

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