Water Chemistry and Molecular Interactions: Electronegativity, Hydrogen Bonds, and Thermodynamics

What does electronegativity measure?

An atom's ability to attract shared electrons toward itself in a covalent bond.

Which atom is more electronegative in water: oxygen or hydrogen?

Oxygen.

Why is water polar?

Oxygen attracts the shared electrons more strongly, giving oxygen a partial negative charge and the hydrogens partial positive charges.

Why are water molecules cohesive?

The partially positive hydrogens of one water molecule form hydrogen bonds with the partially negative oxygen of other water molecules.

How many other water molecules can one water molecule ideally hydrogen-bond with?

Four: it can donate two hydrogen bonds through its hydrogens and accept two through oxygen's two lone pairs.

Why is liquid water described as cohesive yet dynamic?

Its molecules hydrogen-bond to one another, but individual hydrogen bonds break and reform within picoseconds to nanoseconds.

Why does liquid water have high entropy even though it is cohesive?

Transient hydrogen bonds allow each water molecule to sample many different arrangements, or microstates, rapidly.

How does water keep a hydrophilic molecule soluble?

Water forms favorable ionic interactions or hydrogen bonds with the molecule and surrounds it in a hydration shell.

Does water prevent all other molecules from interacting with a dissolved hydrophilic molecule?

No. Water interactions are transient, so potential binding partners can displace water if they form sufficiently favorable interactions.

How does water promote biological membrane formation?

The hydrophobic effect drives nonpolar lipid tails together while polar head groups remain exposed to water, producing a bilayer.

Why are biological membranes necessary?

They create distinct compartments and allow cells to control their internal environment and organize biochemical processes.

Why are covalent bonds generally stronger than individual noncovalent interactions?

Covalent bonds involve shared electron pairs, whereas noncovalent interactions depend on weaker attractions between full, partial, or temporary charges.

What is bond dissociation energy?

The positive energy required to break a bond.

What is bond association energy?

The energy change when a bond forms; favorable bond formation has a negative value.

How are bond association and bond dissociation energies related?

They have equal magnitudes but opposite signs.

Why are multiple noncovalent interactions useful in multistep biological pathways?

Together they provide strong and specific binding, but each interaction is weak enough that the molecules can separate without a large energy input.

How do multiple noncovalent interactions create molecular specificity?

Only a correctly shaped partner can simultaneously satisfy the required charge, polarity, hydrogen-bonding, and van der Waals contacts.

What determines whether an ionic interaction is favorable or unfavorable?

The signs of the two charges: opposite charges are favorable and like charges are unfavorable.

What is the sign of the bond association energy between opposite charges?

Negative, because association is energetically favorable.

What happens to a favorable ionic interaction as opposite charges move closer together?

It becomes stronger and its bond association energy becomes more negative, until steric limits become relevant.

What happens when two like charges move closer together?

Their repulsion becomes stronger and the interaction energy becomes more positive and unfavorable.

How does increasing charge magnitude affect an ionic interaction?

It increases the magnitude of the interaction; for example, +2 and -4 interact more strongly than +1 and -1 at the same distance and dielectric constant.

What property is directly related to a solvent's dielectric constant?

Polarity.

How does a high dielectric constant affect an ionic interaction?

It weakens the interaction by shielding the charges from one another.

What is the equation used for ionic bond energy in the course?

Bond energy = kq1q2/(Dr), where q1 and q2 are charges, D is dielectric constant, and r is distance.

How does the electronegative atom in a hydrogen-bond donor prepare hydrogen for bonding?

It pulls electron density away from the covalently attached hydrogen, giving that hydrogen a partial positive charge.

Why must a hydrogen-bond acceptor have a lone pair?

The lone pair provides concentrated electron density that attracts the donor's partially positive hydrogen.

Which atoms most commonly serve as biological hydrogen-bond donors and acceptors?

Oxygen and nitrogen.

Why can sulfur hydrogen-bond only in some molecular environments?

Sulfur is less electronegative than oxygen or nitrogen, so its ability to create or interact with partial charges depends strongly on its chemical environment.

What four factors affect hydrogen-bond strength?

The identities/electronegativities of the donor and acceptor atoms, distance, angle/alignment, and the dielectric environment.

Why is an O-H hydrogen-bond donor usually stronger than an N-H donor, all else equal?

Oxygen is more electronegative and gives its bonded hydrogen a larger partial positive charge.

How does a van der Waals attraction arise?

Temporary fluctuations in electron distribution create an instantaneous dipole that induces a complementary dipole in a nearby atom.

Why do van der Waals interactions become unfavorable at very short distances?

Electron clouds overlap, producing strong repulsion.

What determines the optimal van der Waals distance between two atoms?

The atoms' van der Waals radii.

Why are van der Waals interactions especially important for nonpolar groups?

Nonpolar groups cannot make strong ionic interactions or conventional hydrogen bonds, so close packing and van der Waals contacts provide much of their favorable enthalpy.

What is a hydrophobic interaction?

The apparent association of nonpolar surfaces in water, driven mainly by the hydrophobic effect and aided by van der Waals contacts.

What occurs during the hydrophobic effect?

Nonpolar molecules cluster, reducing water-exposed nonpolar surface area and releasing ordered water molecules into bulk water.

What is the main energetic driving force of the hydrophobic effect?

A favorable increase in the entropy of water.

Why is water at a nonpolar surface entropically unfavorable?

It cannot hydrogen-bond favorably with the surface and must adopt a limited set of ordered arrangements to preserve hydrogen bonds with other water molecules.

What does a negative ΔG indicate?

The process is thermodynamically favorable or spontaneous under the stated conditions.

What does a positive ΔG indicate?

The process is thermodynamically unfavorable and requires coupling or energy input to proceed.

How does bond formation affect ΔH?

It releases energy, giving a favorable negative contribution to ΔH.

How does bond breaking affect ΔH?

It requires energy, giving an unfavorable positive contribution to ΔH.

How does increased disorder affect ΔS?

It produces a positive and favorable entropy change.

In ΔG = ΔH - TΔS, how does a negative ΔH affect ΔG?

It lowers ΔG and is favorable.

In ΔG = ΔH - TΔS, how does a negative ΔS affect ΔG?

It makes -TΔS positive, raising ΔG and opposing the process.

At what temperatures does entropy have a larger effect on ΔG?

Higher temperatures because the entropy term is multiplied by T.

If a process is favorable at low temperature but unfavorable at high temperature, what is the likely sign of ΔS?

Negative; increasing temperature makes the unfavorable -TΔS contribution more positive.

What is a Brønsted-Lowry acid?

A proton donor.

What is a Brønsted-Lowry base?

A proton acceptor.

Does a higher pKa describe a stronger or weaker acid?

A weaker acid that holds its proton more strongly.

Which form predominates when pH is below pKa?

The protonated acid form.

Which form predominates when pH is above pKa?

The deprotonated base form.

What is the Henderson-Hasselbalch equation?

pH = pKa + log([base]/[acid]).

What is [base]/[acid] when pH equals pKa?

1:1.

What is [base]/[acid] one pH unit above pKa?

10:1, which is about 91% base and 9% acid.

What is [base]/[acid] one pH unit below pKa?

1:10, which is about 9% base and 91% acid.

Why do weak acids buffer effectively within approximately one pH unit of their pKa?

Both acid and base forms are present in meaningful amounts, allowing the buffer to absorb added OH- or H+.

Which phosphate pair buffers near physiological pH?

H2PO4- and HPO4^2- because the relevant pKa is about 7.2.

How does phosphate respond to an influx of H+ near pH 7.4?

HPO4^2- accepts H+ and becomes H2PO4-, limiting the pH decrease.

How does phosphate respond to an influx of OH- near pH 7.0?

H2PO4- donates H+ to OH-, forming HPO4^2- and water and limiting the pH increase.

Which phosphate form cannot act as a Brønsted-Lowry acid?

PO4^3- because it has no proton left to donate.

At pH 7.5 with phosphate pKa 7.2, what is the approximate HPO4^2-/H2PO4- ratio?

10^0.3:1, approximately 2:1.

Does changing pH change the pKa of an ionizable group?

Not by itself. pKa is determined by the group and its local environment; pH changes the ratio of protonated to deprotonated forms.

What structural features are shared by the standard amino acids?

An alpha carbon bonded to an amino group, a carboxyl group, a hydrogen, and a variable side chain.

Why are amino acids usually drawn as zwitterions near physiological pH?

The alpha amino group is mostly NH3+ and the alpha carboxyl group is mostly COO- at physiological pH.

Which standard amino acid is achiral?

Glycine because its alpha carbon is attached to two hydrogens.

What is the difference between the D/L and R/S naming systems?

D/L describes configuration relative to glyceraldehyde, whereas R/S assigns absolute configuration using priority rules.

Which stereoisomer is used for almost all amino acid residues in proteins?

The L-isomer.

What are the names and codes for glycine?

Glycine; Gly; G.

What are the names and codes for alanine?

Alanine; Ala; A.

What are the names and codes for valine?

Valine; Val; V.

What are the names and codes for leucine?

Leucine; Leu; L.

What are the names and codes for isoleucine?

Isoleucine; Ile; I.

What are the names and codes for methionine?

Methionine; Met; M.

What are the names and codes for proline?

Proline; Pro; P.

What are the names and codes for phenylalanine?

Phenylalanine; Phe; F.

What are the names and codes for tryptophan?

Tryptophan; Trp; W.

What are the names and codes for serine?

Serine; Ser; S.

What are the names and codes for threonine?

Threonine; Thr; T.

What are the names and codes for tyrosine?

Tyrosine; Tyr; Y.

What are the names and codes for cysteine?

Cysteine; Cys; C.

What are the names and codes for asparagine?

Asparagine; Asn; N.

What are the names and codes for glutamine?

Glutamine; Gln; Q.

What are the names and codes for aspartate?

Aspartate; Asp; D.

What are the names and codes for glutamate?

Glutamate; Glu; E.

What are the names and codes for lysine?

Lysine; Lys; K.

What are the names and codes for arginine?

Arginine; Arg; R.

What are the names and codes for histidine?

Histidine; His; H.

Which six larger nonpolar amino acids strongly prefer the protein interior?

Valine, leucine, isoleucine, methionine, phenylalanine, and tryptophan.

Why do most large nonpolar side chains occur in a soluble protein's interior?

Burial reduces water-exposed nonpolar surface area and releases ordered water through the hydrophobic effect.

Why is glycine often found on protein exteriors, turns, and loops?

Its side chain is only hydrogen, so it exposes little nonpolar area and provides exceptional backbone flexibility.

Why does alanine show little preference for the interior or exterior?

Its methyl side chain is small enough that exposing it to water has only a modest energetic cost.

Why is proline often found in turns and loops?

Its cyclic side chain restricts backbone rotation and can create bends, while its relatively small nonpolar surface is tolerable on the exterior.

Why can tyrosine occur on either the protein interior or exterior?

It has a polar hydroxyl group but also a large nonpolar aromatic surface.

Which three amino acids are commonly phosphorylated in eukaryotic proteins?

Serine, threonine, and tyrosine.

What feature allows serine, threonine, and tyrosine to be phosphorylated?

Each has a side-chain hydroxyl group.

Which amino acids are normally positively charged near pH 7?

Lysine and arginine; histidine may be positive depending on its pKa and local environment.

Which amino acids are normally negatively charged near pH 7?

Aspartate and glutamate.

What is a salt bridge in a protein?

A favorable noncovalent interaction between oppositely charged functional groups, often positively and negatively charged side chains.