Some Properties of Water

Some properties of water

Hydrogen bond network

Solvation under the microscope

Oil and water does not mix at equilibrium essentially due to entropy

Substances that does not mix with water Substances that does mix with water  hydrophobic  hydrophilic – Lipids. – Hydrogen peroxide – Carbohydrates – Salts

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 2 Water is asymmetric and polar Water molecule is highly polar • Almost all electron density shifted from hydrogen towards oxygen. • Average electron density around O in a water molecule about 10 times that around H. • Latter are essentially naked protons. Water molecule (slightly) bent

Angle between O and two Hs almost equal to value of 109.5° found in perfect octahedron.

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 3 Water is asymmetric and polar Water molecule is highly polar • Almost all electron density shifted from hydrogen towards oxygen. • Average electron density around O in a water molecule about 10 times that around H. • Latter are essentially naked protons. Water molecule (slightly) bent

Deviation due to steric hindrance between O lone pairs, which repel bond between this atom and H.

Two highly polarized OH bonds forming an angle other than π add up to create 1.8 D net dipole moment

In addition to dipole, water has higher non-zero spherical multipole moments:

- linear quadrupole - square quadrupole - linear octupole - cubic octupole

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 5 Water is asymmetric and polar Water is highly polar High net dipole moment gives water high polarization. Water molecules align themselves: • With respect to one another and with respect to ions.

• In external electric field (partly counterbalances thermal agitation).

Without electric field With external field • Microwave oven use this principle to induce high frequency oscillations of water molecules (eventually contained in food). Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 6 Water H-bond network A water molecule can form up to four H-bonds • Each water can accept two Hs via O lone pairs, and donate two Hs. • Since lone pairs and OH bonds sit on almost perpendicular planes, local tetrahedral order arises, which creates open structure and 3D bonding network. • Solid water (ice) features indeed tetrahedral arrangement of waters, with two Hs at ~0.1 (arms) nm and two at ~ 0.18 nm (legs) from central oxygen.

• Typical distance of H-bond in water (0.18 nm between H and O) longer than covalent bond and shorter than sum of H and O atomic radii (0.26 nm). • Due to very small size of H in water, which behaves almost like naked proton. • Tetrahedral arrangement of water arises when T lowers and thermal disorder becomes less dominant  water molecules get locked in a perfect crystal featuring void spaces. • Reason for anomalous decrease of density when water cooled below 4 °C.

Boiling points of elements of Groups 15, 16, 17 bound to H atoms

Boiling point of compounds containing first element in each group abnormally high (particularly true for water).

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 9 Water H-bond network H-bond in water stronger than in similar H-bonding liquids

• H-bonds in water stronger than in other H2X solvents: e.g. hydrogen sulfide (H2S) much weaker H-bond capability than water because of lower electronegativity of S (2.6) compared to O (3.5). • Despite higher bending angle of two Hs around S (92° vs. 104.5°), weaker

dipole (~1D) than water. Essentially H2S molecules interact via vdW forces. 

• H2S gas at room temperature even though it has twice the molecular mass of water. Other H-bonding liquids cannot form so many bonds • Hydrogen fluoride, ammonia, methanol cannot form four hydrogen bonds, either due to an inability to donate/accept hydrogens or due to steric effects. • None shows anomalous behavior of thermodynamic, kinetic or structural properties like those observed in water.

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 10 Water H-bond network Liquid water compromise between H-bond optimization and entropy • When T > 273 K water melts because thermal energy partly disrupts ordered arrangement of tetrahedrons into hexagonal array. • Liquid water as collection of many small ice-like fragments.



Partially ordered state maintained in liquid phase.

• Each water molecule surrounded on average by ~4 nearest neighbors. • Each water molecule forms on average ~2.5 out of 4 possible H-bonds at any time: - Arrangement may consist of one pair of more tetrahedrally arranged strong H-bonds (one donor D and one acceptor A) with remaining hydrogen bond pair being either ~6 kJ/mol weaker, less tetrahedrally arranged, or bifurcated. - Division of water into higher (4-linked) and lower (2-linked) H-bond coordinated water at any time seen in computer simulations of water dynamics at room temperature.

Partially ordered state maintained in liquid phase.

• Each water molecule surrounded on average by ~4 nearest neighbors. • Each water molecule forms on average ~2.5 out of 4 possible H-bonds at any time: - At room T, X-ray spectroscopy shown that 80% of molecules in liquid water have one (cooperatively strengthened) strong H-bonded OH group and one non-, or only weakly, bonded OH group at any instant (sub-fs averaged). - Remaining 20% made of four-H-bonded tetrahedrally coordinated clusters. - Much debate as to whether such structuring represents the more time-averaged structure... even if instantaneous H-bonded arrangement is tetrahedral, distortions to electron density distribution may cause H-bonds to have different strengths.

When solvated, small nonpolar molecules (typically gases) or polar molecules with large hydrophobic moieties get trapped into "cages" of H-bonded, frozen water molecules, called clathrates

• Water molecules reorganize around solute forming a clathrate cage (chemical substance consisting of lattice trapping or containing molecules).

• Allows atoms to maintain H-bonds with each other in nearly preferred tetrahedral orientation: average number of H-bonds not drop very much when small nonpolar object introduced.

When solvated, small nonpolar molecules (typically gases) or polar molecules with large hydrophobic moieties get trapped into "cages" of H-bonded, frozen water molecules, called clathrates

• Energetic cost not significant. • Entropic cost important! 1. Waters lining cage cannot point any of four H-bonding sites towards solute and still remain fully H-bonded. 2. Outside nonpolar surface water H-bonds constrained to lie parallel to surface of solute.  Loss of orientational freedom by water.

When solvated, small nonpolar molecules (typically gases) or polar molecules with large hydrophobic moieties get trapped into "cages" of H-bonded, frozen water molecules, called clathrates

• Balance between optimizing electrostatic interactions and reduce loss of entropy. • At room T entropic term dominates ΔF of solvation for small nonpolar objects.

• Propane – C3H8 – dissolved in water:

ΔH=-3.2 kBT

-TΔS=9.6 kBT 

ΔF=6.4 kBT Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 17 Solvation of nonpolar molecules

When solvated, small nonpolar molecules (typically gases) or polar molecules with large hydrophobic moieties get trapped into "cages" of H-bonded, frozen water molecules, called clathrates

TΔS source of Hydrophobic effect  Poor water solubility of nonpolar molecules at room T

Large non polar objects (C60) are also embedded by clathrate cages

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 19 Solvation of nonpolar molecules Clathrates have different but well-defined structures

Gas hydrates usually form two crystallographic cubic structures (types I and II) and seldom, a third hexagonal structure (type H).

• Made of 46 water molecules, forming two types of cages: - Small: 512. - Large: 51262. • Typical guests gases forming

type I are CO2 and CH4.

• Made of 136 waters, also forming two types of cages: - Small: 512. - Large: 51264.

• Formed by gases like O2 and N2.

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 22 Solvation of nonpolar molecules Type H Unit Cell • Made of 34 waters, forming three types of cages: - Small: 512 and 435663. - Large: 51268. • Requires solvation of two guest gases (large and small) to be stable.

Butanol (C4H9OH)

Pentanol (C5H11OH)

Hexanol (C6H13OH)

Heptanol (C7H15OH)

Hydrophobic solvation very complex phenomenon, but something can be understood from experiments, showing a decrease of solubility as T increases.

Butanol (C4H9OH) • Translational and rotational Pentanol (C H OH) 5 11 entropies of every molecule of solute increase upon solvation. Hexanol (C6H13OH) • However, for any solute molecule Heptanol (C H OH) 7 15 many water molecules decrease their orientational entropies.

• Higher number of solute particles  larger net decrease of S • Increasing T makes free energy change larger  Decreasing solubility

• 6 different ways for any H2O to H-bond with two nearest neighbors in liquid water. • When nonpolar molecule inserted in water, number of possible H-bonding configurations reduces to 3, because waters constrained on surface.

ΔS = Sonly−water − Swater+hydrophobic ΔS = N k lnW − k lnW A ( B only−water B water+hydrophobic )

ΔS = N A (kB ln6 − kB ln3)

ΔS = N AkB ln2 TΔS ≈ 0.42 kcal / mol

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 27 Solvation of nonpolar molecules Entropy key to hydrophobic solvation Hydrophobic Solvent molecule cage • Hydrophobic molecules stick together to minimize water-exposed area.

• Less surface area exposed: - fewer water molecules loose entropy - lower energetic penalty  Leads to poor solubility and eventually total phase separation.

Solvation free energy roughly proportional to solute surface area

• Due to short range of H-bond interaction, H-bond network disrupted only in first layer surrounding nonpolar object.  • Free energy cost of creating interface (and cavity) roughly proportional to surface area.

Verified experimentally as solubility of hydrocarbon chains decreases with increasing chain length.

• Clathrate structures can only form around sufficiently small solutes. • Whit too large objects waters cannot maintain tetrahedral arrangement of H-bonds.  • Being less constrained, entropic cost is not as high as for small nonpolar solvents. • Enthalpic component of solvation becomes key to solvation (smaller value of average number of H-bonds).  Magnitude of hydrophobic effect for large solutes similar to that for small molecules.

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 30 Hydrophobicity General definition based on thermodynamic preference for polar vs. non-polar solvents: Hydrophobic substance characterized by positive Gibbs energy of transfer from a non-polar to a polar solvent (depends on solvents!).

Quantify hydrophobicity of a small molecular group R by its hydrophobicity constant

Soct/wat π = lo g oct/wat S0

• S  ratio of molar solubility of compound R-A in octanol (non-polar) to that in water

• S0  ratio of molar solubility of compound H-A in octanol to that in water

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 31 638 17 MOLECULAR INTERACTIONS internuclear distance between formally nonbonded atoms is less than their van der Waals contact distance, which suggests that a dominating attractive interaction is pre- sent. For example, the O–O distance in O–H···O is expected to be 280 pm on the basis of van der Waals radii, but is found to be 270 pm in typical compounds. Moreover, the H···O distance is expected to be 260 pm but is found to be only 170 pm. Hydrogen bonds may be either symmetric or unsymmetric. In a symmetric hydrogen bond, the H atom lies midway between the two other atoms. This arrangement is rare, but occurs in F–H···F −, where both bond lengths are 120 pm. More common is the unsymmetrical arrangement, where the A–H bond is shorter than the H···B bond. Simple electrostatic arguments, treating A–H···B as an array of point charges (partial negative charges on A and B, partial positive on H) suggest that the lowest energy is achieved when the bond is linear, because then the two partial negative charges are furthest apart. The experimental evidence from structural studies sup- ports a linear or near-linear arrangement.

(f) The hydrophobic interaction Nonpolar molecules do dissolve slightly in polar solvents, but strong interactions between solute and solvent are not possible and as a result it is found that each indi- vidual solute molecule is surrounded by a solvent cage (Fig. 17.9). To understand the consequences of this effect, consider the thermodynamics of transfer of a nonpolar hydrocarbon solute from a nonpolar solvent to water, a polar solvent. Experiments indicate that the process is endergonic (∆transferG > 0), as expected on the basis of the increase in polarity of the solvent, but exothermic (∆transfer H < 0). Therefore, it is a large decrease in the entropy of the system (∆transfer S < 0) that accounts for the positive Gibbs energy of transfer. For example, the process

CH4(in CCl4) → CH4(aq) Fig. 17.9 When a hydrocarbon molecule is has ∆ G =+12 kJ mol−1, ∆ H = −10 kJ mol−1, and ∆ S = −75 J K−1 mol−1 surrounded by water, the H O molecules transfer transfer transfer 2 at 298 K. Substances characterized by a positive Gibbs energy of transfer from a non- form a cage. As a result of this acquisition of structure, the entropy of the water polar to a polar solvent are called hydrophobic. decreases, so the dispersal of the It is possible to quantify the hydrophobicity of a small molecular group R by hydrocarbon into the water is deﬁning the hydrophobicity constantHydrophobicity, π, as entropy-opposed; its coalescence is S Deﬁnition of entropy-favoured. π = log oct/wat [17.26] S S hydrophobicity constant 0 π = log oct/wat S0 where S is the ratio of the molar solubility of the compound R–A in octanol, a • Positive values of π indicate hydrophobicity, negative values indicate nonpolar solvent, to that in water, and S0 is the ratio of the molar solubility of the compoundhydrophilicity H–A in octanol (thermodynamic to that in water. preference Therefore, for positive water valuesas a solvent). of π indicate hydrophobicity and negative values of π indicate hydrophilicity, the thermodynamic • Experiments show that π of most groups do not depend on nature of A. preference for water as a solvent. It is observed experimentally that the π values of most groups do not depend• onAdditive the nature properties of A. However, of groups: measurements do suggest group additivity of π values, as the following data show:

RCH3 CH3CH2 CH3(CH2)2 CH3(CH2)3 CH3(CH2)4 π 0.5 1.0 1.5 2.0 2.5

Thus, acyclic saturated hydrocarbons become more hydrophobic as the carbon chain length increases. This• Explained trend can by be increase rationalized in Δ Hby and ∆ decreaseH becoming in ΔS more positive of transfer with increase in numbertransfer of carbons in chain. and ∆transfer S more negative as the number of carbon atoms in the chain increases. At theBiophysics molecular Course held level, at Physics formation Department, University of a of solvent Cagliari, Italy. cage Academic around Year: 2017/2018. a hydrophobic Dr. Attilio Vittorio molecule Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 32 involves the formation of new hydrogen bonds among solvent molecules. This process is exothermic and accounts for the negative values of ∆transfer H. On the other Solvation of polar molecules

Small molecules such as sugars are soluble at room T

• Some H-bonds are formed between water and solute molecules. • Compensate for entropic penalty due to presence of sites functioning only as acceptors or donors on surface of molecule.

Small polar molecules interact electrostatically with water, even if no H-bonds are formed

• If no H-bonds are formed, entropic penalty must be paid as for nonpolar objects.

• However, electrostatic interactions compensate for loss of orientational entropy by waters.

• Strong electrostatic (ion-dipole) interactions stabilize structures formed by water around ions. • Water molecules around small cations highly polarized  Strengthening in their donor H-bonding towards other solvent molecules

H-bond energies of 2+ Zn (H20)5HO-H···OH2, + ZnCl (H20)4HO-H···OH2,

ZnCl2(H20) 3HO-H···OH2

are 426%, 277% and 23% stronger than HO-H···OH2 bond.

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 36 Solvation of ions Dominant forces on ions (and polar molecules) in aqueous solution  Short range chemical interactions involving effective partial charge transfer from the ion or charged atom to water Namely… - Spare outer electrons on water interact with cations/positively charged atoms. - H-bonds donated from water interact with anions/negatively charged atoms.

Resulting interactions with water rather different: • Anion/H-bond interactions enthalpically much greater than cation-lone pair electron interactions for same size ions. • Due to closer approach of atoms in first case.

• Solvation energy of monovalent cations and anions well described by continuum model that includes electrostatic, dispersion, and cavity contributions showing that water molecules outside these influences have little net difference from bulk water. • Presence of ions stabilizes water clusters over their state in bulk, as they reduce H-bonding exchanges and proton mobility of affected water molecules. • Effect on clustering extends out to:

- 3-4 hydration shells [~(H20)130] for weakly hydrated ions

- 7-9 shells [~(H20)400] for strongly hydrated cations (but good H-bonding capabilities retained).

• (H20)20 water clathrates surround monovalent cations. • Also in this case, several defined structures possible:

- Tetrahedral cavity (c) in puckered water + + dodecahedra by H3O and NH4 . - Octahedral cavity (d) could be occupied by many monatomic cations and anions having six waters in their (inner) hydration shell (Na+, K+, Cs+, Ca2+, Cl-, Br-), while allowing a fully hydrogen-bonded second shell. - Cubic cavity (b) may be occupied by 3+ charged lanthanoid or actinoid ions with coordination number of eight.

Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2017/2018. Dr. Attilio Vittorio Vargiu PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course. 40 References • Books and other sources • Atkins, Physical Chemistry 9th ed., chap. 17 • http://www1.lsbu.ac.uk/water/water_structure_science.html