# Tutor profile: Gavin S.

## Questions

### Subject: Organic Chemistry

(This format will be a bit wordy, since I cannot draw chemical structures here. Use Google and/or your knowledge of chemical naming to help you see the structure of each compound below!) Atropine is an antimuscarinic drug that inhibits the parasympathetic nervous system. It is commonly used against nerve agents and pesticide poisonings, and is on the World Health Organization’s List of Essential Medicines. a) (Simple) Estimate the $$\mathrm{p}K_a$$ (in water solvent at room temperature) of both atropine and its conjugate acid. b) (Intermediate) A total synthesis of atropine is proposed below. Fill in all the missing compounds (A—F). Not all byproducts are shown. succinaldehyde + methylamine + acetonedicarboxylic acid $$\rightarrow$$ A A + 2 HCl + heat $$\rightarrow$$ B (+ 2 CO2 + 2 Cl-) B + C $$\rightarrow$$ tropine 2-chloropropane + Mg $$\rightarrow$$ D 2 D + phenylaceticacid $$\rightarrow$$ E + 2 C3H8 E + formaldehyde $$\rightarrow$$ F F + H2SO4 $$\rightarrow$$ 3-hydroxy-2-phenylpropanoic acid tropine + 3-hydroxy-2-phenylpropanoic acid $$\rightarrow$$ atropine c) (Simple) Atropine can be racemic at the benzyllic position. In slightly acidic conditions, racemic atropine can become a diastereomeric. Draw all 4 possible stereoisomers that can form from protonating racemic atropine, and predict the most stable stereoisomer. d) (Challenge) Predict the most major product of atropine reacting with methyl bromide. This product will have 2 methyls: predict whether these methyls will give the exact same chemical shift as each other in 1H and in 13C NMR. If you predict they will give different chemical shifts in either (or both) 1H or (and) 13C NMR, predict which methyl will be more deshielded. Explain.

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### Subject: Chemistry

You wish you were in Funnyverse, an alternate universe, so you study the properties of this universe compared to ours as you plan out life there. a) (Simple) Write the stable electron configuration for the most stable form of each of the elements in the 1st 3 rows of the periodic table in our universe. For example, the stable electron configuration for the most stable form of the element with atomic number $$Z = 18$$, argon (Ar), is $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^2 3{p_y}^2 3{p_z}^2$$. b) (Challenge) In Funnyverse, the magnetic spin quantum number $$m_s$$ does not exist. Given this, recreate the 1st 3 rows of the periodic table in Funnyverse, where each row ends with an element whose atom has its outermost energy level (valence shell) filled. Label each element with its atomic number $$Z$$, rather than the typical name used in our universe.

a) The electron configuration of an element is the assignment of every electron in an atom of this element to an orbital. The most stable electron configuration (or “ground state” electron configuration) of an element can be determined by a few principles: 1) Aufbau (“building-up”) principle: The electrons are distributed among the available orbitals by filling the lowest-energy orbitals first. 2) Pauli exclusion principle: Every electron must be distinguishable. Since every electron can take 1 of 2 magnetic spin quantum number values $$(+\frac{1}{2} \, \mathrm{or} \, -\frac{1}{2})$$, this allows up to 2 electrons to occupy the same orbital. 3) Hund’s rule: When there are unfilled subshells of degenerate orbitals, the most stable electron configuration is the one that maximizes the total magnetic spin quantum number. This can be interpreted as maximizing the parallel electron spins when they are in degenerate orbitals. These rules can be summarized as: The most stable, valid electron configuration of an element is the one that minimizes the total energy (Aufbau principle, Hund's rule) while ensuring every electron is distinguishable from each other (Pauli exclusion principle). Based on these, the 1st 3 rows of the periodic table in our universe would be: Z = 1 (hydrogen, H): $$1s^1$$ Z = 2 (helium, He): $$1s^2$$ Z = 3 (lithium, Li): $$1s^2 2s^1$$ Z = 4 (beryllium, Be): $$1s^2 2s^2$$ Z = 5 (boron, B): $$1s^2 2s^2 2{p_x}^1$$ or $$1s^2 2s^2 2{p_y}^1$$ or $$1s^2 2s^2 2{p_z}^1$$ Z = 6 (carbon, C): $$1s^2 2s^2 2{p_x}^1 2{p_y}^1$$ or $$1s^2 2s^2 2{p_y}^1 2{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^1 2{p_z}^1$$ Z = 7 (nitrogen, N): $$1s^2 2s^2 2{p_x}^1 2{p_y}^1 2{p_z}^1$$ Z = 8 (oxygen, O): $$1s^2 2s^2 2{p_x}^2 2{p_y}^1 2{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^1 2{p_y}^2 2{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^1 2{p_y}^1 2{p_z}^2$$ Z = 9 (fluorine, F): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^1 2{p_z}^2$$ or $$1s^2 2s^2 2{p_x}^1 2{p_y}^2 2{p_z}^2$$ Z = 10 (neon, Ne): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2$$ Z = 11 (sodium, Na): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^1$$ Z = 12 (magnesium, Mg): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2$$ Z = 13 (aluminum, Al): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_y}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_z}^1$$ Z = 14 (silicon, Si): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1 3{p_y}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_y}^1 3{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1 3{p_z}^1$$ Z = 15 (phosphorus, P): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1 3{p_y}^1 3{p_z}^1$$ Z = 16 (sulfur, S): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^2 3{p_y}^1 3{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1 3{p_y}^2 3{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1 3{p_y}^1 3{p_z}^2$$ Z = 17 (chlorine, Cl): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^2 3{p_y}^2 3{p_z}^1$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^1 3{p_y}^2 3{p_z}^2$$ or $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^2 3{p_y}^1 3{p_z}^2$$ Z = 18 (argon, Ar): $$1s^2 2s^2 2{p_x}^2 2{p_y}^2 2{p_z}^2 3s^2 3{p_x}^2 3{p_y}^2 3{p_z}^2$$ b) With the magnetic spin quantum number, up to 2 electrons in the same orbital could be distinguishable from each other $$(+\frac{1}{2} \, \mathrm{or} \, -\frac{1}{2})$$. Thus, by the Pauli exclusion principle, up to 2 electrons could occupy any given orbital in our universe. In Funnyverse, the immediate consequence of not having a magnetic spin quantum number $$m_s$$ is that electrons in the same orbital are no longer distinguishable from each other. As a result of the Pauli exclusion principle, every orbital can now only be occupied by at most 1 electron, not 2. Since all other quantum numbers $$(n, l, m_l)$$ do not depend on the magnetic spin quantum number, they remain unaltered. The 1st 3 rows of the periodic table in Funnyverse are thus: Z = 1: $$1s^1$$ Z = 2: $$1s^1 2s^1$$ Z = 3: $$1s^1 2s^1 2{p_x}^1$$ or $$1s^1 2s^1 2{p_y}^1$$ or $$1s^1 2s^1 2{p_z}^1$$ Z = 4: $$1s^1 2s^1 2{p_x}^1 2{p_y}^1$$ or $$1s^1 2s^1 2{p_y}^1 2{p_z}^1$$ or $$1s^1 2s^1 2{p_x}^1 2{p_z}^1$$ Z = 5: $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1$$ Z = 6: $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1$$ Z = 7: $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_x}^1$$ or $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_y}^1$$ or $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_z}^1$$ Z = 8: $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_x}^1 3{p_y}^1$$ or $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_y}^1 3{p_z}^1$$ or $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_x}^1 3{p_z}^1$$ Z = 9: $$1s^1 2s^1 2{p_x}^1 2{p_y}^1 2{p_z}^1 3s^1 3{p_x}^1 3{p_y}^1 3{p_z}^1$$

### Subject: Biology

One of the most promising and popular technologies developed in molecular biology this decade is the CRISPR/Cas9 genetic engineering system: this tool can be introduced into a cell to manipulate the cell’s DNA, greatly facilitating how biologists engineer cells and holding promise to cure genetic diseases. a) (Simple) The CRISPR/Cas9 system comprises 2 components: a gene expression system for a nuclease (Cas9) and a gene expression system for a RNA molecule, called the guide RNA (gRNA). What is a nuclease, and what is a RNA molecule? Include in your answers the type of biomolecule it is and its most common known function. b) (Challenge) When used in eukaryotic cells, like human cells, the nuclease Cas9 is typically expressed using a promoter that is specific for RNA polymerase II (RNAP II); the RNA molecule (gRNA) is typically expressed using a promoter that is specific for RNA polymerase III (RNAP III). Rationalize why the Cas9 is typically expressed using a RNAP II promoter, yet the gRNA is typically expressed using a non-RNAP II promoter.

a) A nuclease is an enzyme capable of cutting DNA. Nearly all known nucleases are proteins and cut either a single strand of DNA or both strands of a double-stranded DNA. These cuts may be highly sequence-specific and/or specific to the shape of the DNA site (though it is arguable that sequence-specificity is at its core shape-specificity). An RNA molecule is one of the two major types of nucleic acids found in the cell—the other is DNA. RNA is chemically different from DNA by having a hydroxyl group (-OH), rather than a hydrogen (-H), at the 2’ position of its ribose sugar ring, making the RNA molecule generally more flexible in structure, versatile in function, and shorter-lived than DNA. As a polymer (chain), RNA typically serves as a temporary template of information, encoded in its sequence of nucleotides (containing A, C, G, and/or U) which selectively interacts with other molecules based on the RNA sequence. As a monomer, RNA molecules, particularly ATP, alternatively serve as high-energy units that can power other cellular processes that would otherwise be too slow and/or unlikely to occur. b) To approach this problem, we must connect two realizations: (1) The Cas9 nuclease and its gRNA are both expressed from genes, but they are different types of biomolecules and thus must be produced by different mechanisms. Specifically, while both components require their genes to be transcribed, the Cas9 nuclease is a protein and thus also requires translation, while the gRNA does not. This differentiation must be encoded in one of the production steps that both share; otherwise, the cell would not know which RNA transcript should be designated for translation and which must remain an RNA molecule. (2) There are 3 major types of known promoters, each of which recruits a different set of transcription machinery—the one with RNA polymerase I (RNAP I), RNA polymerase II (RNAP II), or RNA polymerase III (RNAP III)—specific to that promoter. Among these 3 types of promoters, only the one recruiting RNAP II is known to produce messenger RNA (mRNA), which in turn is the only RNA known to be designated for translation. Thus, it would be most reasonable to use a promoter specific for RNAP II to express the Cas9 nuclease, which we want as a protein. The 2 remaining promoters—the ones for RNAP I and RNAP III—do not designate the produced RNA for translation, so the resulting RNA is, after some post-transcriptional processing, free from binding to ribosomes and is ready to use with the Cas9.

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