supra up to part 9 hatcher

how can stereoselectivity of a chemical reaction be achieved with artificial enzymes?

modify the structure of the chemical catalyst (primary interactions) and the protein environment (secondary interactions)

how can cancer cells be exploited for drug delivery?

they have specific molecular markers

they are recognised by specific types of proteins, namely antibodies

this can be exploited for drug delivery

what ae antibodies?

y shaped protein produced by b cells, a specific type of ehite blood cell

used to recognise foreign objects, such as bacteria and viruses, collectively referred to as antigens

what is the structure of an antibody?

the y is made with a heavy chain, the sides of the y has light chains

disulfide bonds connect the chains to themselves

the ends of the y have a variable region with a smaller hypervariable region inside

how do foreign bodies connect to an antibody?

there is an epitope on the end of the foreign body that connects to the variable region on the antibody

why is it difficult for anions to pass through the membrane?

different permeability coefficients (Cl- »» K+)

metal cations absorb more strongly onto the phospholipid head groups

dipole layer at the interface of an unpolarised membrane (out -, in +)

water molecules align - dipolar OH bonds are directed at the phosphate oxygens in the phospholipid head groups

how should a transporter of anions across the membrane be designed?

provide hydrogen bond donors

water soluble

cell penetrating agent (CPA)

what are the benefits of using synthetic nucleoside triphosphate transporters (SNTTs) to transport NTPs into cells?

operationally simple, selective, rapid and gentle

no apparent damage to plasma membrane or drop in cell viability

transported ntp is rapidly liberated from the complex and available for incorporation into dna

what is DNA templated synthesis (DTS)?

three components: oligonucleotides, a reactive group that participates in the chemical reaction, a linker than connects the first two

performed at relatively diluted concentrations, but enough to enable single-stranded dna to bind to each other

annealing (binding) of the ssDNA will initiate the reaction

what is the role of the initiator complex in DTS?

binds to the cargo forming

cargo - carrying a growing reactant at the 3’ end

has toehold domains for binding to other dna molecules

what is the role of the instruction hairpins in DTS?

controls the sequence of reactions

has single stranded toehold domains complementary to its partners

what is the role of the chemistry hairpins in DTS?

carries reactive building blocks

contains sequence that anneals (binds) to the corresponding instruction hairpins

contains a short sequence that anneals to the cargo end

what is the role of keys in DTS?

toehold domains interact with them specifically

all hairpins have hidden specific sequence and only exposed when the hairpin is removed

what happens to the 4-stranded complex called the Holliday junction?

it undergoes resolution, which is thermodynamically favourable driven by the binding of toehold hybridisation and opening the hairpin loop

this exposes bases that can then bind to the initiator strand

where is the aldehyde functionality in DTS

cargo always contains it during the elongation process

what is a sigma hole?

a positively charged “hole” that a halogen or hydrogen bonds can donate into

what is the negative belt?

just behind the sigma hole

in a halogen bond it is the halogen donor

what are the similarities between halogen and hydrogen bonds?

both have same bond angle (155-180)

both have same bond length (2.5 - 3.8 A)

what are the differences between halogen and hydrogen bonds?

halogen bonds are orbital and electrostatic, hydrogen bonds are just electrostatic

halogen bonds have energy 5-200 kJ/mol, hydrogen bonds have energy 15-160 kJ/mol

halogen bonds compete with solvents with donor atoms (e.g. pyridine, DMSO)

hydrogen bonds compete with (are weakened by) polar solvents

what is the key difference between halogen and chalcogen bonds?

chalcogen bonds have two sigma holes but halogen bonds only have one

when there are heteroatoms in ring systems, what do you need to be aware of?

keeping any lone pairs apart from each other

although, sigma hole stabilisation can outweigh lone-pair repulsion

what is the nature of a hydrogen bond?

it is primarily electrostatic in nature (charge and dipole) but with some covalency (molecular orbital interaction)

ideally 180 degrees but usually 140-180 degrees

what makes strong and weak hydrogen bonds?

very strong: H-F …. F-, RCOO- …. HN+(R2)

strong: O-H … O, O-H….. N, N-H …. O

moderate: N-H …. N

weak: Cl3C-H …. O, Cl3C-H …. N, O-H….. pi ring/bond

what is the nature of strong, moderate and weak hydrogen bonds?

strong - quite covalent

moderate - mainly electrostatic

weak - electrostatic

what are the types of H-bond geometry?

simple - just a H-bond

bridged - two H bonds to one acceptor

bifurcated - make a triangluar shape with either one donor and two acceptors or two donors and one acceptor

cyclic - each species has a donor and acceptor and they make a cycle of H bonds

what impacts the cooperativity of a host and guest molecule with regards to H bonds?

the more H bonds, the stronger the association constatnt

degree of preorganisation (entropy)

tautomerisation (enthalpy)

nature of substituents (enthalpy)

what is the secondary electrostatic effect?

when there are multiple hydrogen bonds in a row, need to account for any additional attractive or repulsive electrostatic interactions

what are some examples of non-canonical basepairing?

Hoogsteen edge

Watson Crick edge

(TAT)n

hemiprotonated cytosine dimer

G quartet

what is the secondary bonding interaction?

intramolecular bond distances that are longer than normal bonds and intermolecular distances that are shorter than van der waals

what impacts the strength of a halogen bond?

stronger for nucleophillic or lewis basic acceptors

stronger when there is an electron withdrawing group on the halogen and it is more polarisable (I>Br>Cl>F)

what are some halogen bond donor examples?

dihalogen molecule

haloalkane

haloarene or haloheteroarene

1-haloalkyne

halonium ion

haloimide

what are some examples of halogen bond acceptors?

lone pair possessing atom

pi system

anion

what are some enthalpy driven intermolecular interactions?

coulomb energy

ion-dipole interaction

dipole-dipole interaction

dipole-induced dipole interaction

van der waals (dispersion) interaction

aromatic pi interaction

hydrogen bond

halogen bond

what happens to the enthalpy of hydration as ionic radius increases?

the enthalpy of hydration becomes more negative and the ionic radius decreases

what happens to the cavity diameter as the crown ether gets bigger?

the cavity diameter increases as the crown ether gets bigger

what happens to the binding constant as the preorganisation increases?

the binding constant increases with increasing preorganisation

why are macrocycles produced at low concentrations?

high dilution disfavours the rate of intermolecular reaction (polymerisation) so cyclisation is encouraged (intramolecular)

what can be used as a template in crown ether synthesis?

metals that can coordinate to the oxygens

how can you favour macrocycle production, besides doing it at low concentration?

reduced the number of conformers

want to disfavour the anti conformer and favour the gauche conformer

what are the major enthalpic contributions to anion binding?

coulombic

metal coordination

multipolar interactions (usually hydrogen bonding)

challenges arise from the variety of shape and protonation state

how can carbonyl groups interact with eachother?

in an antiparalle, orthogonal or a displaced parallel fashion

a strong interaction occurs when the distance between the atoms is shorter than the sum of their van der waals radii

what are some of the supramolecular interactions in biology? (5 interactions)

hydrogen bonding - base interactions in DNA/RNA, protein-protein, protein-ligand interactions

non-covalent electrostatic interactions - protein-DNA, protein-protein binding, protein folding

pi-pi interactions - protein residues, protein-base interactions

dispersion forces (van der waals) and hydrophobic effects - protein folding, oligomeric interactions

coordination bonds - metal coordinations

what are some common host-guest relationships in supramolecular chemistry?

host ligand, guest metal

host enzyme, guest substrate, ligands

host receptors, guest substrate

host receptors, guest ligands and drugs

host antibody, guest antigen

what are the 4 bases? (names, general structure, pairing interactions etc)

thymine, adenine, guanine and cytosine

guanine and adenine have a two ring structure, thymine and cytosine have a one ring structure

thymine and adenine pair by 2 hydrogen bonds

guanine and cytosine pair by 3 hydrogen bonds

what is the structure of DNA?

antiparallel complementarity

one side 3’ → 5’, other side 5’ → 3’

DNA forms a double helix

how can you separate a double helix of DNA?

enzymes such as rna polymerase

heat (melting)

which strand of dna does the rna polymerase transcribe?

the antisense strand (template strand)

this is the 3’ → 5’ strand

why is dna good to work with?

can be easily prepared

20 to 50-mer can be commercially obtained with desired modifications

larger pieces can be obtained with a polymerase chain reaction

reasonably stable >ph 7, 20-50 degrees celcius

can be stored in solid, water and buffered conditions

what are the applications of transporting chemically modified nucleoside triphosphates (NTPs) into cells?

treating viral infections, treating cancer, dna research, bioanalysis, new genetic alphabets

what is the role of the plasma membrane?

control the transportof cargo across the cell

transport of anionic compounds into cells is a great challenge

what are ion channel mimics and mobile carriers?

ion channel mimics - ion conductance pathway

mobile carriers - small molecules that shuttle ions from one side to the other

what is protein folding dictated by?

sequence

van der waals interactions

electrostatic interactions

disulfide bonds

metal coordination

secondary structure

tertiary and quarternary fold

what is the secondary protein structure?

beta pleated sheets

alpha helices

coils

what is a shaker protein?

membrane bound protein that conducts K+ ions from outside to inside the cell

maintains cell resting potential and conducts electrical signals

why are shaker proteins selective for K+ over Na+?

both K+ and Na+ are in water shells under aqueous environment

shaker contains a narrow K+ selectivity filter GYG

this has carbonyl groups binding to the ion and strip water out of the ion shell

for K+, the filter frees water off readily but for Na+ the filter is too rigid and wide to interact with the smaller ion

basically K+ fits perfectly inbetween the 4 carbonyl groups, but Na+ doesnt so cant coordinate to all 4 at once

how do shaker proteins permeate quickly?

there are 4 K+ binding sites

geometry of the protein favours alternated occupancy i.e. two potassium ions each time

high electrostatic repulsion

the intracellular domain contains a vestibule which is an aqueous cavity that can stabilise K+ by solvation

how can dissociation constants be measured?

isothermal titration calorimetry

why do people make artificial enzymes?

enhanced biocompatibility of the chemical catalysis

creating a hybrid catalyst means chemical catalysts to function in an aqueous environment in the presence of biomolecules and inside cell

secondary interactions between the chemical catalysts and designated protein environment allow for additionsl level stereochemicsl control

what are the challenges with dynamic kinetic resolution?

enantioselectivity of the kinetic resolution needs to be sufficiently high

the enzyme and racimisation catalyst need to be compatible

rate of racimisation needs to be sufficiently higher (10x) thsn the rate of the undesired reaction

racimisation catalyst needs to be compatible with the products formed in the enzyme reaction

how can artificial enzymes be made?

anchoring chemical catalysts in a protein environment

what is self assembly?

spontaneous association of molecules under non-equillibrium conditions into meta-stable structurally well defined aggregates joined by non-covalent interactions

what happens to the nmr spectrum with slow and fast exchange?

for fast exchange, as ligand concentration decreases, there will still be one defined peak that moves slowly to the other ppm

with slow exchange, the second peak growns as the first decreases in size

what is a cyclodextrin?

a cyclic oligosaccharide composed of n alpha-D-glucopyranoside units

symmetric arrangement of asymmetric units

what is a job plot?

plots mole fractions vs concentration

the maximum point is where the concentrations of the host and guest are in a 1:1 ratio

what is an example of linear chain polymerisation?

pi stacking

what is an example of ring-chain polymerisation?

ditopic H bonding

what is isothermal titration calorimetry?

technique used to determine the thermodynamic parameters of interactions in solution

you inject your guest into the host solution and this can be compared to a reference solution of the solvent

what are the three models for indefinite self association?

isodesmic model - non-cooperative, K1 = K2 = K3 etc

nucleation elongation model - cooperative K2 < K3 = K4, sigma = K2/K

attenuated growth model - K2 > K3 > K4

how can you determine if there are interactions between two amino acids?

introduce a point mutation at site A in both proteins

if the difference in free energy changes is non-zero then there is an interaction between the two sites on the protein

what are some of the enthalpy driven intermolecular interactions?

coulomb energy

dipole dipole interaction

dipole induced dipole interaction

ion dipole interaction

van der waals

aromatic pi interaction

hydrogen bond

halogen bond

when are dispersion interactions (van der waals) the dominant interaction?

when the contact surface is large, i.e. in pi stacking

what is the pi stacking distance?

3.4 angstroms

what does the electrostatic potential map of benzene look like? how does this impact pi stacking?

mostly negative in the middle getting more positive as you move out

they stack with the hydrogen of one benzene over the ring of another as there is an atractive force between them

if benzene and fully flourinated benzene were to pi stack, how would this look?

fluorine is electronegative so it makes the center more positive and the outside more negative

when they stack, they stack over eachother perfectly due to the attractive forces between them

how do substituents on benzene effect its ability to bind a cation?

electron donating groups improve its ability to bind cations because they make the aromatic system more electron rich

it is therefore more negative in the center of the electrostatic potential map, so can bind positively charged cations better

what are anion pi interactions?

non covalent interactions of anions with electron deficient aromatics

electrostatic in nature

anions are often found above the ring centroid

why are photoactive mofs good for photocatalysis?

solid - ease of separation from products

porous structures - large pores and possible guest diffusion allows reactants to be included inside the MOF sturcture, promoting efficient interaction with catalytic sites

high surface area - porous structures increases surface area - increased chance of reactants interacting with catalytic sites

versatile design space - enables tuning of optical properties for optimal absorptionand efficient catalytic activity

semi conductors - mobile charge carriers are required to facilitate redox processes necessary for catalysis

what functionalisation strats can be used to insert photo-initiated redox centers in mofs for photocatalysis?

inorganic cluster nodes - designed to be redox active semiconductors

linker ligands - include organic chromaphores or metal organic dyes

encapsulate catalytic guest molecules inside pores

what are COFs?

covalent organic frameworks

all organic crystalline structures that are formed of nodes and linkers

conatin only light atoms (H B C N O)

nodes and linkers are covalently bound

stronger bonding and robust 3D organic networks

what are some applications of cofs?

gas storage/separation, guest encapsulation/exchange, catalysis, drug delivery, photoswitches, optoelectronics

why are cofs better for drug delivery than mofs?

mofs can lead to toxic metals leaching into the body

what are hofs?

crystalline structures formed of molecular monomer units that are linked by hydrogen bonding interactions

the monomer units could be carboxylic acids, amides, imidazoles

can be constructed by identical and non-identical hydrogen bonding groups

what the negatives of binding force being weaker in hofs than in mofs or cofs?

hof solids are less stable

pore expansion is more difficult

activation of hofs is more challenging

what are the positives of the binding force being wesker for hofs than in mofs and cofs?

hofs are more soluble

highly crystalline cofs sre more readily formed

hofs are more processible - implications for device manufacture

what are the applications of hofs?

gas adsorption/storage/separation, chemical separations, optical applications, drug delivery

why do we need to characterise supramolecular material?

confirm structure

understand properties and reactivity

what are static techniques?

timescale is irrelevant - properties dont change with time

examples: mass spec, elemental analysis, chemical analysis

what is the electromagnetic spctrum from low to high frequency?

radio

microwave

infrared

visible

ultraviolet

x ray

gamma ray

what are the areas in the UV/vis region?

electronic absorption nm

raman cm^-1

luminescence nm

what is the beer lambert law?

A = e x c x l

A = sbsorption

e = molar extinction coefficient

l = length between sample and detector

what types of transition can you get with uv/vis?

non-bonding → pi antibonding

pi bonding → pi antibonding

non-bonding → sigma antibonding

pi bonding → sigma antibonding

sigma bonding → pi antibonding

sigma bonding → sigma antibonding

what is the effect of conjugation on uv/vis?

bathochromic shift

shift to lower energy

what is an lmct?

ligand to metal charge transfer

molecular pi bonding orbital of ligand → molecular sigma antibonding orbital of metal

what is an mlct?

a metal to ligand charge transfer

molecular pi bonding orbital of metal → molecular pi antibonding orbital of ligand

what is internal conversion?

radiationless (vibrational) relaxation within the states of the same multiplicity(S2 → S1)

what is intersystem crossing?

radiationless transition between the states of different multiplicity (S1 to T1)

what is fluorescence?

radiative transition between the states of the same multiplicity (spin allowed, S-S)

what is phosphorescence?

radiative transition between the states of different multiplicity (spin forbidden, S-T)

what are the timescales of the different uv/vis transitions?

absorption - femto seconds (10^-15)

internal conversion - pico seconds (10^-12)

intersystem crossing - molecule dependent

fluorescence - 1-1000 nanoseconds (short)

phosphorescence - 1-100 milliseconds (long)

what is stokes shift?

a small shift between absorption and emission spectra

Eem < E abs

atoms always moving so reaction coordinate not ever perfectly aligned

absorption and emission spectra tend to be mirror images

only true if geometries of ground and excited state are very similar