The AONSA Prize Lecture
Neutrons for Chemistry - Challenge and Opportunity
22 July 2015
At the outset I would like to thank AONSA as well as the organisers and sponsors of this lecture
and the AONSA prize - which I am honoured to receive.
I show this first slide of the dawn at Manly on 22 July 2015 as this underlines what I really want to
say in this lecture. Although the lecture is historical in my search for the use of neutrons inchemistry, I hope to show that we are really at the dawn of that usefulness through the marvelous
and massive improvements in neutron scattering methods over the last 50 years.

Dawn at Manly, NSW, 22-7-15
I have subtitled the lecture “Challenge = Opportunity (in soft matter 1963-2015)” to focus on thechallenge and opportunity that neutron scattering offers to chemistry. What are some key challenges
for chemistry using the remarkable properties of neutron scattering as a method of understanding
phenomena in solids and liquids?
I speak first of all about chemistry and the slide below shows a complex chemical synthesis ofgiberrellin – a natural product that promotes plant growth. My colleague Professor Lew Mander isfamous for this work. He is an excellent chemist and each step in the 23 stage synthesis from 1gramof starting material, ending up with 0.1gm of giberrellin, has been carefully planned and choosing
the many different reagents used to go from one step to the next with maximum efficiency isunderpinned by a great knowledge and understanding of chemical reactions.

The steps in the total synthesis of Giberellin A1 – a plant hormone
These reactions occur in solution and the phenomena that are occurring are on the scale ofAngstroms and timescales of the order of picoseconds. Chemical knowledge and intuition guidemany synthetic chemists – our hope is to understand the microscopic phenomena for predictive
purposes. Another chemical example which begs to be understood in microscopic detail on thesespace and time- scales is polymerization. This is illustrated below.

Chemical control of polymerisation outcomes by solvent and catalyst

On the left hand side a free radical initiation of the polymerization is indicated for styrene, to makepolystyrene, one of the world’s most important plastics. At each step a new radical is formed, one
molecule longer than the previous. The reaction may proceed with great speed, transforming1020
monomer molecules in a period of minutes or hours, depending on the conditions – the reaction
could be explosive if it went too quickly. Three possible products are shown also in the figure. The
wonderful thing for a chemist is that the outcome of isotactic syndiotactic and atactic forms of thepolymer (which have different physical properties and uses) can be controlled by the choice ofsolvent, temperature and catalyst.
The process again occurs at very short times and over short distances and it is the clustering and theelectrostatic properties of the solvent around the reacting molecules at the instant of reaction that
determines the outcome as shown at the bottom of the slide. From the number of molecules
transformed the shoert timescales of these processes can be inferred.

A Tradition in Physical Chemistry at Oxford
How did I come to be focusing my attention on exploring the possibilities of neutron scattering forchemistry at the age of 25 and when I had just become a permanent member of the staff at Oxford
University? I was fortunate to be given a scholarship to come to Oxford to do my DPhil under thesupervision of Dr Rex Richards, at that time a Fellow of Lincoln College and who subsequently
became Vice Chancellor of Oxford University. Rex had been the pioneering chemist of nuclear

magnetic resonance in England for determining chemical structure. He had wound his own
electromagnet in the Physical Chemical Laboratory at Oxford and faced the challenge of seeing
what could be done in chemistry – while most of the work in magnetic resonance was going on inphysics laboratories.
His supervisor was Sir Harold Thompson, also shown it the slide who, in his turn, had been thepioneer of the use of infrared spectroscopy for chemistry since the 1930s. The slide also shows Sir
Cyril Hinshelwood who at the time of my going to Oxford was Dr Lee’s Professor Physical
Chemistry and a Nobel laureate for his work on physical methods of following the rates of physicalreactions. He was the supervisor of Sir Harold Thomson and told me that his supervisor, Sir Harold
Hartley – in the old Balliol-Trinity laboratories – when doing work on electrochemistry had beenaccused of doing physics. Hartley had replied “what you call physics, we call chemistry”. My
doctoral work with Rex Richards and a subsequent short post-doctoral period had resurrected Rex’s
old magnet and been aimed at finding the usefulness of the Overhauser effect for chemistry – a very
open-ended project but which worked extremely well. On my appointment as a Fellow of St John’sCollege and laboratory demonstrator at Oxford, Sir Cyril Hinshelwood had the policy that - as there
was one magnetic resonance expert in the laboratory (Rex Richards) I had to find a new area. It wasa very good policy.
My good fortune was to meet Dr Peter Egelstaff from the Atomic Energy Research Establishment at
Harwell at dinner in St John’s College in 1962 as the guest of Sir Roger Elliott. Peter was interested
in the dynamics of liquids using neutron scattering and, in particular in ortho and para hydrogen –of which I knew something as a chemist. It was Peter who introduced me to neutron scattering
which became my focus subsequently and the “opportunity” was his having just installed at the
DIDO reactor at Harwell a first high efficiency liquid hydrogen cold source as shown below.

Peter Egelstaff and the 4H5 cold neutron scattering Instrument

This was one of the best instruments of its time and I was attracted, as a spectroscopist, by the factof no optical selection rules and by applying the spectroscopic angular dependence of the neutron
spectrum. Using the Q,ω space of neutron scattering was and is the method’s principal challenge –this space contains the signatures in time and distance on the picosecond timescale – the “heart” ofunderstanding diffusion limited chemical reactions.
The possibility of a direct link between the scattering spectrum and models for the molecularmotions through space/time correlation functions was highly attractive and relevant to the sorts ofthings I had been teaching as fundamental ideas for the reactivity of molecules in solution. As an
example of the “cage effect” which chemists talk about for polymerization, the “itinerant oscillator
liquid model” of Varley Sears (Proc Phys Soc 1965, 86, p953) was very close to the notions which
chemists had for fast inter-molecular reactions.

The Egelstaff Neutro-Centric DiagramPeter Egelstaff at that time was just publishing his book of chapters by neutron practitioners andtheorists. In it and in the second paper of the work that Julia Higgins did with him (on zeolites) is
the first example of what we and Peter called the “Egelstaff Neutro-centric” diagram. It showed(left hand side) how neutrons then embraced the region of 0.1 <Q/ Å-1 < 10 in momentum transfer
and 1011 to 1013 sec-1 in frequency – space and time domains around 1Å and 1 picosecond. The
complementarity of neutron scattering to other methods was clear. It was and remains a most

exciting challenge to use this space to characterize structure and dynamics. By 2010 (RHS) the
space had greatly increased in its dimensions illustrating the wide scope that we now have and someof which I will illustrate in this lecture.
In 1963 it was evident to me that because of the absence of optical selection rules – andaccessibility of all molecular motions – some method was needed to simplify the exploration of(Q,ω) space. This point was driven home to me early in 1963 by my first experiment with Peter
Egelstaff to look at the dynamics of liquid and the liquid crystalline phases of para-azoxyanisole on
the 4H5 spectrometer. NMR had shown how different these two phases were but in neutron
scattering at that time, the spectra looked very similar. Isotopic and atomic contrast looked to be theway to distinguish the motions of interest from all the rest. This was the first and remains a key
feature of our use of neutron scattering. The contrast we looked to in the first instance was thatprovided by the great incoherent scattering of hydrogen compared to deuterium, oxygen and silicon
and our first experiments were directed by this.

Isotopic contrast in Neutron Scattering
Julia Stretton-Downes (my first PhD student) and I worked with Peter Egelstaff to detect the
motions of trapped molecules in quinol clathrates. The quinol molecule shown in the slide below
makes a cage because the hydroxyl groups at each end of the benzene ring join with those of othermolecules to seal a box in which molecules as big as methyl cyanide or methanol can beincorporated. Julia produced the fully deuterated quinol using heavy water and the hydrogenation
apparatus in the Dyson Perrins Laboratory and our first paper “localized vibrations of trappedmolecules” appeared in Physical Review Letters 1966, 17, 533-536.

Isotopic Contrast to explore host – guest dynamics
The time of flight neutron inelastic scattering from the included methyl cyanide molecule (upper
curve) is qualitatively different and clearly differentiated from that of the deuterated host lattice(lower curve). The spectra show the “rattling modes” of the included molecule and their coupling to
the host lattice dynamics. With only about 60 data points in the whole time of flight spectrum thefine structure was blurred.

Molecular Dynamics in Zeolites

Use of the “natural contrast” between an included hydrogenous molecule and the alumino-silicate
lattice of zeolite frameworks was also studied at that time to define the residence time and internal
diffusive properties of molecules and these industrially important catalyst materials. The paper in
the Society of Chemical Industry publication 1968 “Molecular Sieves” pp306-318, sets out many of
the theoretical principles and interpretation of the dynamics of trapped molecules. The data show
very little broadening of the quasi elastic peak, strong modification of the low frequency dynamics
and (inset) the importance of rotational diffusion for the trapped molecules. As spectrometers have
improved over the past 50 years, this subject continues to be of interest. It is not only because themolecular dynamics can be recorded but also because of the great changes in the low frequency
liquid spectrum as well as the quasi elastic region are apparent and depend upon the molecularproperties as shown below.

Dynamics of Ammonia, Methyl cyanide and Methyl Alcohol in Molecular Sieve 3A
In this preliminary phase of exploring neutron possibilities for chemistry, the use of contrast to
simplify the spectra of polymers and molecular liquids was also studied. In polymers, there wasgreat interest in identifying the torsional and low frequency motions of methyl groups – thought tobe important for understanding polymer relaxation phenomena and phase transitions (this interest
continues to this day where the onset of methyl group rotation has been used to characterize thesoftening of protein dynamics (see for example the lecture by Katherine Woods in this conference).
Lacking the funds and the competence to perform methyl group deuteration we did an experimentto identify the methyl groups by comparing the neutron scattering from isotactic poly acetaldehydeand ply trifluoroacetaldehyde – where the hydrogens have been replaced by fluorine on the methylgroups. This spectrum published in 1967 shows the major changes in the density of states for themolecular motions – clearly identifying the methyl torsional region of the methyl group spectrum.

Identifying Methyl torsions in Polymers – Atomic Substitution
For molecular liquids, the aim was to see whether the dynamics of one part of the molecule weredifferent from that of another. The objective, ultimately, was to look at molecules in which fast
proton exchange was occurring and to identify the signature of such diffusion limited chemical
reactions. That the two parts of a molecule give different spectra is shown by the contrast variation
experiment on methanol published in the discussions of the Faraday society, 1967, 43, pp169-183.

Separating the Dynamics of different parts of the same molecule by Isotopic Contrast

This paper not only shows separately the dynamics of the methyl group and the OH group on theseliquids but was also our first foray into the dynamics of strong acid solutions – subsequently
followed up by George Stirling and by Andrew Taylor (in his DPhil thesis). Andrew did aremarkable job successively eliminating effects of centre of molecule diffusion and molecularrotation to try to identify (with Jean-Claude Lassegues) the possible signature of the fast protontransfer. Modern spectrometers with variable resolution in the picosecond time-range willundoubtedly add to these pioneering measurements.
MOLECULAR SPECTROSCOPY

Calculation of Neutron Inelastic scattering spectra.
Molecular spectroscopy by inelastic neutron scattering was explored in parallel with the above. The
dynamics of trapped molecules had left us with the impression – which Julia dubbed “the first lawof neutron scattering” – that all neutron spectra looked very similar. There had been beautiful
experiments done by Iyngar, Venkataraman and their colleagues on ammonium salts showing theharmonics of the torsional vibrations in solids but no attempts to demonstrate calculable neutron
inelastic scattering spectra from molecular solids. Philip Reynolds, as an Honors student at Oxford,
undertook this for the molecules in para dichloorbnezene and 1,2,4,5-tetrachlorobenzene crystals.
We were helped in 1967 by a new cold source in 4H5 (the supernova) and by the construction of a
new spectrometer in the DIDO reactor (the 6H instrument) in which George Stirling played a very
big part with Peter Egelstaff and George Haines. This instrument had carefully engineered flightpaths and with Philip’s calculated the hydrogen amplitude weighted density of states for themolecular vibrations showed the potential of using both the eigen vectors and frequencies inassignment and development of molecular force fields.. Discussions of the Faraday Society 1969,

48, pp131-147, conclusively shows the correspondence between the calculated and the observed
spectrum for 1,2,4,5 tetrachlorobenzene and opened up many possibilities for molecular
spectroscopy. Nervousness about the validity of the 1-phonon approximation, the lack of cubic
symmetry, multiple scattering effects and anharmonicity which had surrounded discussions about
the observability of molecular vibrations in “soft” materials was removed.

Calculated and Observed Hydrogen Amplitude weighted INS Spectrum
Comparison of the infrared spectrum of cobalt tetracarbonyl hydride in the vapour and the neutron
inelastic scattering spectrum in the solid in the same energy region (JWW White and CJ Wright
Chemical Communications, 1970 p970) illustrates the value of hydrogen eigen-vector weighting asa contrast method in molecular spectroscopy.

Comparison of Infra-red and Inelastic neutron scattering spectra

The neutron spectrum is simpler and different to the infra red spectrum because the infrared strong
carbonyl stretching motions are not very neutron active whilst all molecular bending modes which
couple to the bending motion of the hydrogen atom in this tetrahedral complex are strongly
represented. This method has now become a powerful tool in chemistry – identifying the dynamics
of molecules at interfaces, in catalytic processes, and in polymers since it has been possible to bringpowerful computer modeling to bear to allow coupling between intra- and inter-molecular force
fields to fit the whole density of states region. (eg. J. Howard, T. C. Waddington and C. J. Wright,
Chem. Phys. Lett. 56, 258 (1978), Review of the analysis of molecular vibrations using INS
Nuclear Instr. and Methods in Phys. Res. G.D Kearley et al. A354, 53, 354 (1995); Vibrational
Spectroscopy with Neutrons. P. C. H. Mitchell, S. F Parker, A. J. Ramiez-Cuesta and J.
Tompkinson. World Scientific, 2005.
SURFACE CHEMISTRY
In 1968, surface chemistry seemed to be a promising chemical area in which neutrons could
contribute. Our experiments on zeolites had shown that with “natural contrast” good signal-to-noisefor included molecules could be obtained. Thus, despite opinion “that neutron scattering would not
be useful for studying adsorbed molecules: as neutrons were penetrating radiation….” we decided
to look at the potential of the technique for surface chemistry. Because of the great “polywater”
debate in the early 1970s (that this new form of water with remarkable properties was produced inthin capillaries of high surface area/volume) we decided to study vermiculite and montmorillonite
clays whose water content could be systematically varied in the spaces between the impermeable ca
1nm thick clay platelets.

The figure above shows the way in which the clay sheets, composed of silica tetrahedral packed
around octrahedra containing magnesium or aluminium for example, can be swelled by added
water. In preliminary experiments we discovered quickly that it was essential to have a clay expert
to prepare the hydrate-able clay films and we were greatly helped by the method of Posener andQuirk who sent Stan Olejnik, one of their students, from Western Australia. Stan made the films
and the data were reported in Nature Physical Science, 1972, 236, p16. The clays were swollen byequilibration with water vapour over solutions of known salt concentration up to swellings of 57Å
from about 2Å between the ca 10Å clay sheets. The time of flight spectra of the included water are
shown below.

Neutron time of flight spectra of water in Lithium Montmorillonite at various swellings
The immediate interest was the extent to which the water spectrum changes with water layer
thickness, d. At low energy transfers (time of flight near 800 µ sec metre-1 (the density of states is
progressively reduced as the water layer thins) and the quasi elastic scattering becomes narrower.
(These data again are quite relevant to the effect of hydration on the dynamics of proteins forexample.) Analysis of the quasi elastic scattering (below) shows the strong variation of the low Q
slope of the energy width as a function of Q2 (where Q is the momentum transfer = (4π/λ) sin θ ,and θ is the half scattering angle = 45 degrees here, and λ the neutron wavelength). This slope is ameasure of the self diffusion constant of the water included between the clay sheet.

Energy width of the Quasi-elastic scattering from water as a function of thickness/Å.
The water self diffusion coefficient, D, drops smoothly as a function of inverse thickness as shownby the beautiful scaling below.

Scaling of the Log (water diffusion coefficient) with reciprocal water layer thickness
The logarithm of the diffusion coefficient scales as the reciprocal of the water layer thickness, a
thickness of the order of 5Å. This scaling can be understood in terms of the classicalthermodynamics of a fluid in a capillary structure for which the radius of curvature of the meniscus

is related to the liquid surface tension and the molecular volume (Kelvin Equation). Our scaling
formula assumes that the confinement confers an additional free energy barrier for diffusion to thatof the normal fluid at the measured temperature. Using the Kelvin equation and accepted values forthe surface tension and the molecular volume, a slope of 10.2Å is calculated for the scaling function- compared to the experimental value of 13Å. It should be noted that this thermodynamic
description of the effects of confinement relates to a molecular description of the change in water
free energy involving the kinetics of exchange of the included water between the surface and thecontained ions and noting, that as the water thickness decreases, so also does the relative proportionof these charged species increase – as in a concentrated ionic solution.
In parallel with these water experiments, two students Robert Anderson and Philip Gamlen, studied
the neutron scattering from simple molecules adsorbed on carbon and in graphite intercalation
compounds. Their work, and that of others in France and the USA, showed that thermodynamic
descriptions, such as those provided by adsorption isotherms for these molecules, could be exploredin terms of the interfacial structures. By inelastic scattering from the isoelectronic ammonia andmethane adsorbed on graphite Phil Gamlen showed the consequences of non-wetting of the carbon
surface (ammonia) and registration of the methane at low coverages on the hexagonal close packed
surface. A large extension by Robert Thomas and other colleagues by the discovery of quantum
mechanical tunneling in the inelastic neutron scattering from methane adsorbed on graphite showed
the means of testing intermolecular potentials for the adsorption process by neutron inelastic
scattering.

The structural signature for deutero-methane adsorbed on graphite (to ensure that coherent
scattering from the molecule contributed to the diffraction pattern) is shown below. The strong peakat scattering angle of about 44 degrees in 2 theta gives the 002 reflection of the graphite substrate.
At increasing coverages, provided by increasing the dose of deuterated methane, the growth of a

second peak at 2 theta of about 41 degrees shows the formation of a registered layer of deuterated
methane molecules on the graphite.

Growth of the √3x √3 commensurate layer of CD4 on Graphite with increased dose

Commensurate Adsorption of CD4 on hexagonal graphite
The ease of performing this measurement was greatly facilitated by the availability of the D1Bmultidetector powder diffractometer at the Institut Laue Langevin in Grenoble subsequent to Britain
joining that Institute in 1973. Similarly the discovery of rotational tunneling for adsorbed CH4 on
powdered graphite and its temperature dependence shown below, was possible because of the IN5instrument at ILL. Two broad tunneling transitions on each side of the elastic peak can be seen at
6K, fading away to a broad distribution arising from rotational tunneling by 30K - note the freezing
point of methane is 91K.

First Observation of Rotational Tunnelling by an Adsorbed molecule
By using oriented graphite, the orientation of the graphite C axis and the momentum transfer could
be changed and at the same time the spectrum resolution improved. These data for the momentum
transfer Q parallel and perpendicular to the surface are shown below.

Polarisation of the Tunnelling Spectrum of CH4 on oriented GraphiteSplitting of the methane rotational pocket state levels and their nuclear spin angular momenta
Professor Alfred Huller contributed greatly to the understanding of these spectra and theirassignment. The slide above shows his calculations of the rotational energy levels of the methane
molecule in a tetrahedral field and in the trigonal field (appropriate to adsorption on the surface ofgraphite). For the calculation it is assumed that the molecule is held in a field of methane molecules(tetrahedral field – methane solid) or at the surface (trigonal field). The rotations of the molecules
are hindered by these potentials but because of the low molecular motions of inertia about its
molecular axes, tunneling between the “pocket states” of the librations occurs. A key differentiator
between the tetrahedral and trigonal fields is the splitting of the T state (spin angular momentum =1) by the trigonal field. This small splitting of 1.4 µ eV was observable on the same sample using
the ILL back scattering instrument IN10 and allowed several models for the combinedintermolecular and surface potentials responsible for the adsorption to be tested – slide 31. Thesetypes of measurement have since been greatly extended by John Larese and others to test adsorption
potentials for metal oxide surfaces relevant to catalysis and thus provide a way to detailed andchemically useful information.
CHEMICAL REACTIONSThe subject of chemistry is concerned with chemical reactions as well as structures and so we turnto examples in which neutron scattering can provide detailed information on reaction chemistry.
Finding the mechanism of formation of zeolite catalysts and the production of highly crystalline
catalyst films – chemistry in solution and at interfaces. The first example was to find out how
molecular templates direct the formation of the zeolite ZSM-5, a material which can catalyticallyconvert methanol to the aromatic molecule paraxylene. This work was undertaken subsequent to1985 when I was an Argonne Fellow at the Argonne National laboratory in Chicago over a five year
period. That opportunity allowed me (at the invitation of the Director, Walter Schriesheim) to makecontact with any division at the Argonne Laboratory and talk about their work with them. This wasa happy process which resulted in several collaborations, the one here with Lennox Iton (Materials
Physics and Chemistry Divisions) and others at the Intense Pulsed Neutron Source, including myvery able former pupil Frans Trouw and colleague Stephen Henderson.

Argonne National Laboratory 1986- 1990 Collaboration
It was Lennox Iton who drew my attention to a challenge in a recent review that “zeolite
crystallization is one of today’s most complex chemical problems. More than 100 different types ofzeolites have been synthesized under very different conditions. This synthesis of new structures isstrongly influenced by many aspects of the basic gel chemistry such as gel composition, pH,temperature, digestion time, starting materials etc and also by the cations used in the synthesis (BMLock, TR Cannon and CA Messina 1985). This was an exciting challenge with wide scope and one
where neutrons could be useful.

Snug fit of p-Xylene in ZSM-5, tetrahedral template molecule & the ZSM-5 channel structure

The structure of this zeolite, ZSM-5 containing the paraxylene molecule is shown above. The”snugness” of the molecule in the crystal is the key to the discrimination of this catalyst against
other substituted benzenes. Its high porosity, (above) helps its efficiency as a catalyst. The
tetrapropyl ammonium ion template molecular shape and the structure it produces in hydrothermal
synthesis are also illustrated.
We supposed that the directing effect of the template to assemble the silicate species in solution
would result from the structuring of the gel upon addition of the tetrapropyl ammonium ion. We did
not suppose that this would happen at room temperature but that we would eventually see
incorporation of the ion into the gel in the hydrothermal synthesis at high temperature (the final
porous zeolite catalyst has to be prepared by burning out the hydrocarbon template with oxidation atelevated temperatures.)

It was thus a surprise to find that even at room temperature, the gel was structured by the template.
This is demonstrated above by the small angle scattering from the gel with no deuterated tetrapropylammonium salt added is strong in 77% D2O: 23% H2O but very weak if the deuterated template had
been added to the room temperature solution. Neutron scattering length contrast matching of thissilica+ deuterated template occurred in the mixture of 77% D2O: 23% H2O. When hydrogenous
tetrapropyl ammonium ions were used, the scattering was strong in 77% D2O: 23% H2O, illustratingthat the hydrogenous template/SiO2 complex had a difference scattering length density to that when
the deuteron template was used.
Contrast variation plots for the soluble silicate gels (square root of the intensity of scattering at zero
Q as a function of the weight percent heavy water in the mixture) show this effect clearly (below).

(Neutron Scattering length)1/2 vs Weight % D2O Contrast Variation plots for ZSM-5 gels.
The contrast matching point for the silica alone is at 66% heavy water, that for the deuterated
template is at 77% and for the hydrogenous template at 56%. These results show that the silica gel
is organized by the template at room temperatures to structures which have the stoichiometry of theformed catalyst silicate template ratio. In parallel with experiments using a nanoparticle silicate
source for the synthesis, no such structuration occurred although for both synthesis heating underhydrothermal conditions produced the same final catalyst material.

Schematic of the Template hydrophobic + charge effect on soluble silicate gel structureWe invented the idea of “embryo crystals” (above) which are quickly formed on adding thetemplate to the gel and whose structure densifies during hydrothermal process. A number of papers
were subsequently published on this system.

EXPERIMENTS TO FOLLOW UP

Neutron Scattering Distribution functions from 300K soluble silicate gels
The induction of structure at room temperature may be an interesting matter to follow up. The very
high Q scattering possibilities of the IPNS diffractometers allowed us to do some tests of diffractionout to about 30Å-1. The results (below) are for room temperature gel mixtures with templates whichproduce different zeolites from soluble silicate gels. The top image shows the diffraction from theuntemplated unheated gel with strong peaks near 2, 6Å-1 and the lower two are the diffraction
patterns for a tetrapropyl ammonium unheated gel and a tetramethyl ammonium unheated gel.
Obvious differences in these distribution functions suggest that, with modern instrumentation suchas SANDALS at the Rutherford Laboratory ISIS source, and the diffractometers at J-PARC which
can reach 50Å-1, there is much to be discovered of chemical interest in these processes.
CATALYTIC THIN FILMS
Chemical reactions, that produce microporous and mesoporous crystalline films at the air-waterinterface can be followed effectively by neutron and x-ray reflectivity and the neutron contrasts areof particular value for establishing the sequence of reactions as the film grow.
For silicate and titanium dioxide films, the experimental method was simply to mix the reagents
such as a hydrolysable silicon or titanium ethoxide or butoxide with the surfactant template and alittle dilute hydrochloric acid to initiate hydrolysis. The aggregation of the silicate or titanate
oligomers so formed in solution can be controlled by the size of the anion associated with apositively charged surfactant or by the surfactant choice. This synthetic process for soluble silica
and the tetramethyl ammonium ion (as template) is illustrated below.

X-ray reflectivity from a growing template silicate film at the air-water interface

Three stages of the ‘induction period” before a crystalline film is seen are shown in the x-rayreflectivity at the air-water interface as a function of time. Initially (red curve) only a broadreflectivity at about 0.13Å*-1 appeared after about 530 minutes of reaction at room temperature.
This long induction time is characteristic of reactions at the interface and related to the kinetics ofassembly of the templated species which within another 100 or 200 minutes produces the sharp
peak structure characteristic of hexagonal close packing of rod-like micelles at the interface.
Combining neutron and x-ray reflectivity allows the chemical composition of the growing film to bemeasured in a parallel experiment- as the solution chemistry is highly reproducible.

Neutron Contrast Variation shows the changing components in growing templated silicate
film with time.
The left hand side of the above slide shows the reflectivity profiles (where the reflectivity has been
divided by Q4), and two neutron contrasts (proto surfactant on D2O (blue) and deuteron surfactant
on air-contrast-matched-water (ACMW) (red) for times between 10 minutes after mixing and 600
minutes after mixing. The data from these reflectivity measurements (neutron and x-ray) can be corefined as well as the profiles for the individual contrasts. These are shown on the right hand side of
the figure. At short times, the deuteron-surfactant on air-contrast-matched-water (orange curve)
shows the well established scattering and density distribution of surfactant adsorbed at the interface;the x-ray profile (black) shows this also but, in addition, a small peak at about 25Å deeper into thesolution showing that silica oligomers have already adsorbed to the surfactant.
The same features are present in the 60 minute data with the proto-surfactant on heavy water
experiment (blue) showing a small dip in the density profile between about 30 and 55Å. This shows
us the adsorption of a second layer of surfactant beneath the monolayer structure already establishedat the air-water interface. This phenomenon is more pronounced at 200 minutes where thecorresponding layer of deuteron surfactant is visible against air-contrast-matched water. Finally at
600 minutes, three or four silicate layers are already established and the alternating layers of
surfactant (double thickness compared to the surface monolayer) are seen. The figure below shows
the way in which the surfactant and silica are arranged in this growing templated film.

Structure of a templated silicate film growing at the air-water interface
Templated films with mesoporous structure can be grown at interfaces and a good method is to dip
a substrate – such as a clean glass slide repeatedly into a surfactant- silicate or titanate solution at
the correct humidity to maintain the solution phase structure on the surface as the plate iswithdrawn. The chemistry of the synthesis solution can be varied so as to control the porosity andallow doping in the resultant film eg N-doping to a mesoporous TiO2 film for water splitting or
water clean-up applications. Such films may have high crystallinity as well as mesoporosity as
shown by the slide - made by dipping.

Highly Crystalline Mesoproous N- doped TiO2 film
The films are clear and the forced tapping microscope shows the mesoporous structure in them after
the polymeric surfactant used to make them by dip-coating surfactant-containing titanate solution
was done. X-ray reflectivity from that film shows the high degree of crystallinity in the cubic Im3m
space group from grazing incidence small angle scattering perpendicular and parallel to the latter.
The combination of x-ray and neutron scattering is always desirable to obtain additional contrasts to
those available from isotopic substitution.
LIQUID SOLUTIONSTo end this lecture, I want to illustrate the enormous potential of modern neutron scattering
instruments for understanding liquid solutions of central interest to chemistry.

Structure of Liquid water at 25C (Wikepedia) & relative size of the tetramethyl ammonium
ion.

The focus is still on finding out how liquids and solutes contained in them structure the water andmove with respect to one another. The Slide above shows an image of the structure of water (fromWikipedia) with the tetramethyl ammonium cation. Dissolving that cation and its salts into water
will obviously perturb the structure shown. Our experiments in the 1970s using quasi-elastic
neutron scattering showed the strong effect of dissolved salts on the water self diffusion coefficient.
For example, small cations such as lithium have the effect of decreasing the water diffusion
coefficient and are said to be structure-making for that reason. By comparison, dissolving
potassium iodide causes the diffusion coefficient as measured by quasi elastic scattering to increase.
Such ion pairs are said to be structure-breaking. Understanding such effects of the solutes on waterand other solvents is at the heart of chemistry and biology.
Looking a the slide again, it could be supposed that such a big ion as the tetramethyl ammonium ion
would break the water structure – as iodide does. Our experiments in the early 1970s and the late1980s used contrast variation for both the tetramethylammonium ion and the water to investigate
the reciprocal effects of this ion on the water and the water on the motions of the ion. This is a sortof paradigm of what might happen (see later) in protein sensitivity to deuterium.

The neutron time of flight spectra for tetramethyl ammonium ions in water with contrast
variation
The Slide above shows the effect of looking at either the ion (upper curves) or the water in contrast
to the ion (lower curves) on the neutron time of flight spectra at two angles of scattering, 45 degrees

and 90 degrees. The obvious differences here are just as great as those seen for the differently
deuterated methanol molecules in the 1960s or the effects of the water layer thickness in clays
described above. With the instrumentation available in the 1970s, a quasi elastic analysis could bemade for the effect on water by varying the fully deuterated tetra methyl ammonium chloride
concentration. This is shown in the slide below.

Effect of various concentrations of the tetramethyl ammonium ion of water diffusion
In the upper curve, the ratio of the ion to the water is 1/103 molar – water is in great excess and thequasi elastic broadening corresponds to only a slight decrease in the water self diffusion coefficient.
Even this big ion is “structure making” as shown by the 1/4.7 concentrated salt solution in the lower
curve.
What is the effect on the ion? The D2O solutions show this. Comparisons were made with NMR andtracer diffusion measurements of the ion centre of mass diffusion agree with reasonably. Moreinteresting though, is the effect of the tightened water structure on the rotational diffusion of thislarge ion – again this can be measured and is reported – illustrating the reciprocal effect of waterand solvent.
I’ve chosen this example to illustrate a whole range of experiments for the future. It may be possible
through experimental developments first at the ISIS spallation neutron source by Andrew Taylorand Masa Arai who built the MARI spectrometer. Andrew and Masa realized the potential ofcollecting as much of the (Q,ω) space as possible and MARI showed the potential of this for the
crystal and spin dynamics of solids. The idea has come to full flowering – again through Masa Araiand his colleagues at J-PARC in the recent study of liquid benzene by Kikuchi et al (slide 58). With
this J-PARC instrument, the chemically fascinating phenomena of separability of inter-molecularand intra-molecular motions on the timescale of pico seconds has been realized. The data for thesolid benzene (lower curves) in the real space of distance and time compare vividly with the liquid
G(r,t) above.

The great challenge for neutron scattering from liquids has been taken up – with stunning
results.
One can only imagine the possibility of now separating and looking at the itinerant oscillator
behavior of a solute surrounding by its caged liquid as postulated in the long held chemical belief
for solution kinetics. The selective deuteration of the solvent and the solute could produce contrastseparated G(r,t) for the two species. The chemical importance of such measurements would be ofgreat value conceptually.
I wish to end with my most recent experiments, again involving the notion of the effects of asolvent on a solute structure and dynamics. Here the solute is the prevalent blood protein humanserum albumin shown in slide 60 alongside two models of clusters of about 10 water molecules.
The structure of this molecule has been closely studied by x-ray diffraction to a resolution of about
2Å by Curry et al. One of the roles of HSA is to carry fatty acid molecules around the body but it isa general transport protein because its large number of alpha helices all have both hydrophobic andhydrophilic components.

What effects would a change from H2O to D2O have on such a molecule?
In attempting to complete a study of the interaction of HSA with small silica nanoparticles, webecame sensitive to a problem with the molecule itself when it had been fully deuterated in heavy
water as the defatted form.

Dynamic Light Scattering from native and recombinant – deuterated, defatted HSA.
The side above shows the dynamic light scattering measured from a solution fo the native protein(available commercially from Sigma (red) and the sample of recombinant protein produced byexpression of the gene in heavy water by recombinant methods. While the native protein had aradius of gyration of about 4nm, the recombinant material was highly aggregated to particles ofabout 100nm radius. Our current study is to discover the origin of this which may be due to thefactors shown below.

Possible causes of deuterated HSA aggregation
In a collaboration with the deuteration laboratory at the Institut Laue Langevin, Grenoble, eight
different samples of recombinant material have been produced by expression of the gene to producehydrogenous and deuterated protein, in fatted and defatted form, and dissolved in H2O buffer or
D2O buffer. We have no significant differences in the aggregation behavior of these systems.
A clue to the phenomena is in the recent work of Egington and Becket (Biochemistry 2013, 65956600) who have found large solvent isotope effects on protein association thermodynamics (slide65). Their study of the free energy of formation of the homodimer for the biotin repressor protein
indicates a very modest isotope effect from the solvent of about 7 kcal per mole in the free energy.
This, however, is the difference between very large” opposing enthalpic and entropic forces of 41±
3 and -48±3 kcal per mole respectively. For me this illustrates the very subtle balance upon which
nature works and therefore the potentially high effects of subtle changes produced by moleculardeuteration of proteins or a change in solvent, pH, degree of deuteration and salt content. I have no
doubt that neutron scattering combined with light scattering, circular dichroism and carefulcalorimetry will allow the systematics of these phenomena to be uncovered.
Conclusion
This lecture has been mostly about work between 1963 and 1990 - though some things that I highly
prise could not be included. I thank the many students, collaborators and post doctoral colleagues
whose excellence and friendship I have appreciated for many years. I also thank colleagues in all of
the neutron facilities where our work has been done. Without their contribution to the science and to
instrument development neutron scattering would not be where it is today – a key method for
unique understanding of Chemistry, Physics, Biology and the science of Materials.