Arundo donax lectin

Programme and

Book of Abstracts

Fifth Meeting of the Italian (AIC) and

Spanish Crystallographic (GE3C)

Associations (MISCA V)

2

Summary

Committees

………...3

Sponsor

………4

Conference Schedule

………...5

Abstracts

Plenary lectures

….……….………...11

Awards

……….……….………...14

Commercial presentations

……….………..23

MS1 - Crystallography out of Academia

………...27

MS2 - In situ and in operando studies of systems structural evolution……...…31

MS3 - Coordination compounds to coordination materials

………...…..37

MS4 - Crystal growth: from fundamentals to applications in nature and

technology

………..….….44

MS5 - Bio-crystallography: from Structure to Function

………..……51

MS6 - Mineral structures and mineral characterization………..…58

MS7 - Crystal forms in Pharma

……….…..…66

MS8 - Contemporary challenges in Structural Biology

………..…73

Posters of Session 1: MS1

– MS4………...………..….79

3

Committees

Steering Committee

G. Diego Gatta

Fernando Lahoz

Past GE3C President CSIC, Zaragoza

Organizing Committee

Scientific Committee

Luigi Vitagliano

IBB-CNR, Napoli, Chair

Michele Saviano

IC-CNR, Bari, Chair

Filomena Sica

Univ. Federico II, Napoli

Piergiulio Cappelletti

Univ. Federico II, Napoli

Consiglia Tedesco

Luciana Esposito

Rita Berisio

Luca De Luca

Alessia Ruggiero

Nicole Balasco

Annalisa Guerri

Simona Galli

Matteo Alvaro

Giuseppe Falini

Felipe Gándara

Pilar García Orduña

CSIC, Zaragoza

Andrea Ilari

IBPM-CNR, Roma

Sol López-Andres

Univ. Complutense, Madrid

Lucia Maini

Univ. Bologna

Alfonso Martínez de la Cruz

CICBioGUNE, Bilbao

Paolo Pio Mazzeo

Univ. Parma

Marta E.G. Mosquera

4

5

Wednesday, September 4

09:00-10:30

Registration - Centro Congressi

10:30-11:00

Welcome

Luigi Vitagliano (IBB-CNR) and Michele Saviano (IC-CNR), Organizing committee

Opening Ceremony

Pilar Gómez Sal, GE3C President G. Diego Gatta, AIC President Fernando Lahoz, Past GE3C President

Piergiulio Cappelletti, President of the “Società Italiana di Minerologia e Petrologia” Luigi Paduano, Representative of the Chemistry Dept. of Univ. “Federico II”, Napoli Lelio Mazzarella, Emeritus Professor Univ. “Federico II”, Napoli, A memory of

Attilio Immirzi, a founder of the AIC

11:00-12:00

Plenary Lecture 1

Giacomo Chiari (Getty Conservation Institute, Los Angeles) Crystallography in Art and Cultural Heritage

12:00-13:00

Misca Medal - Prize and Presentation

Angeles Monge (ICMM - CSIC, Madrid) About crystals and their properties

13:00-14:30

Lunch & Poster Session 1 (MS1-MS4 Part 1)

14:30-15:50

MS1 - Crystallography out of Academia

Chairs: Alessia Bacchi, Aurelio Cabeza Díaz

14.30-15.00 KN1 - Miguel Ángel García Aranda (Univ. de Malaga) Diffraction for industries, businesses and health

15.00-15.30 KN2 - Irene Bassanetti (Chiesi Farmaceutici, Parma) Crystalline form suitable for inhalation in drug discovery

Oral Presentation

15.30-15.50 O1 - Samuele Ciattini

Determining the concentration of diamond powder deposited on a textile yarn: a multitechnique approach

15:50-16:20

Coffee Break

16:20-18:40

AIC/GE3C Prizes and Presentations

6 Development and application of crystallographic methodologies for powder diffraction 16.50-17.10 Nardelli Award - Federica Bertolotti (Univ. dell’Insubria) Total scattering methods in reciprocal space: developing crystallographic tools for nanostructured and disordered materials

17.10-17.30 XavierSolans Prize-Paul B. Klar (CzechAcademyof Sciences) Ordering patterns in mullite

17.30-17.45 Best PhD Thesis Award - Davide Comboni (Univ. di Milano) High-pressure behavior of microporous materials: crystal-fluid interactions and deformation mechanisms at the atomic scale

17.45-18.00 Best PhD Thesis Award - Luca Mazzei (Univ. di Bologna) Biochemical and structural studies on urease inhibition, a nickel-dependent virulence factor

18.00-18.15 Best PhD Thesis Award - Stefano Racioppi (Chalmers Univ. of Technology)

Electronic properties and chemical bonding in tetrazolate based coordination polymers 18.15-18.30 Fellowship for Abroad Research - Benny Danilo Belviso (IC-CNR Bari)

NSD protein family: a new promising target for epigenetic therapy of tumor diseases 18.30-18.40 Best Graduate Thesis Award - Ida Freda (Sapienza Univ. di Roma)

Engineering murine neuroglobin: structural and functional analysis of the heme sliding mechanism

18:40-19:40

Poster Session 1 (MS1-MS4 Part 2)

20:30

Welcome Party -

Thursday, September 5

9:00-10:00

Plenary Lecture 2

Enrique Espinosa (Univ. de Lorraine, Nancy)

Unraveling intensity, nature and preferential geometries of intermolecular interactions in molecular assembling

10:00-10:30

Coffee Break

10:30-11:00

Commercial Presentations

10:30-10:45 Bruker by Vernon Smith 10:45-11:00 Rigaku by Mark Benson

11:00-13:00

MS2-In

situ

and

in

operando

studies

of

systems

structural

evolution

11:00-11:30 KN1 - Elisa Borfecchia (Univ. di Torino)

X-ray absorption spectroscopy to track structural and chemical dynamics of metal ions in nanoporous frameworks

7 11:30-12:00 KN2 - Laura Canadiñas-Delgado (Centro Universitario de la Defensa de Zaragoza)

Neutron diffraction studies to explore low temperature structural phases of a metal-organic framework

Oral Presentations

12:00-12:20 O1 - Giorgia Confalonieri

The role of pressure and of CHA framework in the differential absorption of ethanol and water from the azeotrope solution

12:20-12:40 O2 - Davide Comboni

Ettringite at high pressure: structure evolution and elastic behaviour 12:40-13:00 O3 - Elisa Rodeghero

Temperature-induced phase transitions in natural metavariscite

13:00-14:30

Lunch & Poster Session 1 (MS1-MS4 - Part 3)

14:30-16:30

MS3 & MS4 - Parallel sessions

MS3 - Coordination compounds to coordination materials

Chairs: Victor Antonio de la Peña O’Shea, Simona Galli

14:30-15:00 KN1 - Ana E. Platero-Prats (Autonoma Univ. of Madrid) Chasing local structures in nanoporous materials using advanced synchrotron X-ray scattering tools

15:00-15:30 KN2 - Volodymyr Bon (Technical Univ. of Dresden)

Development of in situ diffraction techniques for characterization of nanoporous materials during adsorption of gases and vapours

Oral Presentations

15:30-15:45 O1 - Celia Castillo-Blas

Metal-cation arrangement control in secondary building units of metal-organic frameworks and their translation to oxides

15:45 -16:00 O2 - Rebecca Vismara

Mixing bis(pyrazolate) ligands in Zn(II) MOFs for CO2 adsorption, affinity and selectivity optimization: a structural and textural study

16:00-16:15 O3 - Inés Ruiz Salcedo

Proton Conductivity in Sulfate-Containing Lanthanide Nitrilotris-methylphosphonates 16:15-16:30 O4 - Marco Milanesio

Synthesis and structural characterization of a Ce-containing AZO-MOF, showing a complex polymorph landascape

MS4 - Crystal growth: from fundamentals to applications in

nature and technology

Chairs: Simona Fermani, Jaime Gómez Morales

14:30-15:00 KN1 - Rocco Caliandro (IC-CNR Bari)

Protein crystallization in hydrogel composite membranes and deep eutectic solvents 15:00-15:30 KN2 - Ylenia Jabalera (Univ. de Granada)

8 Oral Presentations

15:30-15:45 O1 - Daniele Moscheni

Structure and morphology of CdSe and CdSe@CdS colloidal quantum qots from advanced X-ray scattering techniques

15:45 -16:00 O2 - Jose A. Gavira

Use and overuse of reinforced Cross-Linked Enzyme Crystals 16:00-16:15 O3 - Stefano Canossa

Ultra-stable MOFs across the microscale: novel approach for the size control of Al-frameworks

16:15-16:30 O4 - Jaime Gómez-Morales

Induced nucleation of nanocrystalline apatite on graphene nanoflakes by sitting drop vapor diffusion

16:30-17:00

Coffee Break

17:00-18:30

Poster Session 2 (MS5-MS8 Part 1)

18:30-19:15

Herculaneum Ruins: between Science and Tourism

18:30-18:55 Vito Mocella, (IMM-CNR Napoli)

The quest of lost ancient literature. Synchrotron based techniques reveal the secrets of Herculaneum papyri: letters and ink composition.

18:55-19:15 Lomè Galliano (Professional Tour Guide Campania Region) Presentation of the Herculaneum Ruins

Friday, September 6

8:50-10:00

Plenary Lecture 3

Chairs: Giuseppe Zanotti and Anna Marabotti

Martin Weik (Institut de Biologie Structurale, Grenoble) Watching proteins at work by kinetic X-ray crystallography

(The lecture will be preceded by a short talk in memory of Guido Capitani by Giuseppe Zanotti)

10:00-10:30

Coffee Break

10:30-11:00

Commercial Presentations

10:30-10:45 Malvern Panalytical by Eugenio Casini 10:45-11:00 Thermofisher by Max Maletta

11:00-13:00

MS5 & MS6 - Parallel sessions

MS5 - Bio-crystallography: from Structure to Function

Chairs: Adele Di Matteo, Lourdes Infantes

11.00-11:30 KN1 - Claudia Binda (Univ. di Pavia)

Structural studies on flavoenzymes at the cross-road of drug design and cell biology 11:30-12:00 KN2 - Marian Oliva (CSIC, Madrid)

9 Oral Presentations

12:00-12:15 O1 - Giusy Tassone

Structural characterization of a synthetic mimic of the Photoactive Yellow Protein 12:15-12:30 O2 - Simona Fermani

The last gap in the structural proteome of the photosynthetic CO2 assimilation has been

filled

12:30-12:45 O3 - Mario Milani

Structural and functional characterization of TgpA, a critical protein for the viability of

Pseudomonas aeruginosa

12:45-13:00 O4 - Marta Ferraroni

Dioxygen, an unexpected Carbonic anhydrase ligand

MS6 - Mineral structures and mineral characterization - Aula A

11.00-11:30 KN1 - Cristian Biagioni (Univ. di Pisa)

Advances in mineral crystal-chemistry and the role played by rare minerals Oral Presentations

11:30-11:45 O1 - Carlotta Giacobbe

When diffraction meets tomography: the ferrierite case for the improvement of mineral fibers crystallographic characterization

11:45-12:00 O2 - Matteo Ardit

Vanadium-induced color in calcium aluminates: grossite (CaAl4O7) and hibonite (CaAl12O19)

12:00-12:15 O3 - Gioacchino Tempesta

Crystal-chemical characterization of red beryl by standarless Laser Induced Breakdown Spectroscopy and Single Crystal X-Ray Diffraction: an example of validation of an innovative method for the chemical analyses of minerals

12:15-12:30 O4 - Michelangelo Polisi

Amino acids confinement and condensation in mordenite channels 12:30-12:45 O5 - Donato Belmonte

Thermodynamics, elasticity and phase stability of grossite (CaAl4O7) at high pressure and temperature

12:45-13:00 O6 - Eugenio Casini

Crystal structure and thermodynamic behavior of Bi6Te2O15: the likely structure of the rare mineral pingguite

13:00-14:00

Lunch & Poster Session 2 (MS5-MS8 Part 2)

14:00-16:00

MS7 & MS8 - Parallel sessions

MS7 - Crystal forms in Pharma - Aula A

14.00-14:30 KN1 - Jordi Benet-Buchholz (ICIQ, Tarragona)

Pharmaceutical Co-Crystals: New developments using the ‘in situ’ crystallization with a CO2-laser

14:30-15:00 KN2 - Leonardo Lo Presti (Univ. di Milano)

A crystallographic route to understand drug solubility: the case of 4-aminoquinoline antimalarials

10 Oral Presentations

15:00-15:15 O1 - Andrea Ienco

Computational Investigation on Metoprolol Anisotropic Lattice Expansion 15:15-15:30 O2 - Oleksii Shemchuk

Ionic cocrystals of the molecules of pharmaceutical interest 15:30-15:45 O3 - Lourdes Infantes

Search for multicomponent structures of Nevirapine to improve its physicochemical properties

15:45-16:00 O4 - Claudia Carraro

Designing new Cocrystals based on Essential Oil for agricultural applications

MS8 - Contemporary challenges in Structural Biology -

14.00-14:30 KN1 - Juan A. Hermoso (CSIC, Madrid)

The structure of full-length human phenylalanine hydroxylase in complex with tetrahydrobiopterin

14:30-15:00 KN2 - Beatrice Vallone (Sapienza Univ. di Roma)

Key interactions for iron uptake are exploited by infectious agents as revealed by the cryo-EM structure of the Ferritin-CD71 complex

Oral Presentations

15:00-15:18 O1 - Dritan Siliqi

Shwachman-Diamond Syndrome: SBDS and EFL1 conformational characterization through Small Angle X-ray Scattering and Molecular Dynamics Simulations

15:18-15:36 O2 - Marco Mazzorana

Synergies within Life Science at Diamond: towards the future of structural biology 15:36-15:54 O3 - Daniela Caruso

Structural characterization of the aggregates formed by the members of the GADD45 family

15:54-16:00 Digital Posters

16:00-16:30

Coffee Break

16:30-18:00

General Assemblies (in parallel)

18:00-19:00

Meetings of the subgroups

19:00-19:30

Closing Ceremony

20:30

Social Dinner - Ristorante La Scialuppa

Saturday, September 7

11

PL1: Crystallography in Art and Cultural Heritage

Giacomo Chiari

Gia' Chief Scientist - Getty conservation Institute – Los Angeles - California

Many applications to archaeometry and to diagnostics in the preservation of cultural heritage are based on crystallography. A deep understanding of the material is fundamental for both disciplines. Recently, noninvasive portable instruments have become common, due to (or generating) the present modus operandi that excludes the possibility of taking samples. Because of this, the imaging of various type has become fundamental. These are either based on radiation familiar to crystallographers (X-rays) or based on properties elucidated by them.

This lecture will showcase a series of crystallographic applications in the field of conservation science, from Maya Blue structure (synchrotron and neutron powder diffraction) to Tutankhamen tomb paintings, from Michelangelo’s censure panels in the Sistine chapel to a hidden face under a Rembrandt painting. The most recent tool (XRF scanners) will be compared to a procedure based on a much smaller number of measurements producing very promising results.

I hope that I will be able to highlight the unique contribution that crystallography can make to the widening field of Conservation Science in the preservation of our ever more challenging cultural heritage.

12

Laboratoire de Cristallographie, Résonance Magnétique et Modélisations (CRM2), UMR CNRS 7036, Université de Lorraine, Nancy, France. enrique.espinosa@univ-lorraine.fr

Through the Hellmann-Feynman and Hohenberg-Kohn theorems,1,2 the electron density distribution (r) can be considered the conceptual bridge between the structure and the energetic properties of molecular systems. Accordingly, (r) codes essential features of molecular organization in space. Important aspects such as intensity, nature, and directionality of intermolecular interactions are at the origin of molecular assembling, and therefore of supramolecular structures with important applications in the fields of Crystal Engineering, Supramolecular Chemistry and Material Science. These aspects are not only implicitly coded on

(r) but also in its derived properties, as the Laplacian function 2(r) and the electrostatic potential (r). These three scalar functions bring complementary information to study the assembling of molecules because each of them focuses on a different electronic aspect of the molecular system. Thus, whereas (r) reflects the interatomic and intermolecular interactions taking place in the system, 2(r) and (r) point respectively the regions of the space where

(r) is locally concentrated (2_{(r) < 0) or depleted (}2

(r) > 0) and the molecular electrophilic ((r) > 0) and nucleophilic ((r) < 0) regions.

The topological analysis of any scalar function, which is the analysis of its derivatives, provides richer information than appears from the direct observation of the scalar function itself. In the widely used QTAIM theory,3 this kind of analysis has been deeply developed for (r) to characterize many aspects that this function exhibits in atoms, molecules, and their interactions. In our work, topological developments on the (r), 2(r) and (r) scalar functions have permitted the analysis of (i) the intensity4,5 and nature6,7 of intermolecular interactions, (ii) the geometrical preferences found on molecular assembling8,9 and (iii) the influence zones of molecular electrophilic and nucleophilic sites that are at the origin of molecular recognition and molecular assembling, in particular when dealing with the paradoxical cases of anionic or cationic aggregates.10,11

[1] H. Hellmann Einführung in die Quantenchemie. Leipzig, Vienna: Deuticke, 1937.

[2] R. P. Feynman Phys. Rev., 1939, 56, 340; P. Hohenberg, W. Kohn Phys. Rev., 1964, 136, 864. [3] R. F. W. Bader, Atoms in Molecules: a Quantum Theory, Clarendon, Oxford, 1990.

[4] E. Espinosa, E. Molins, C. Lecomte Chem. Phys. Lett., 1998, 285, 170. [5] E. Espinosa, I. Alkorta, J. Elguero, E. Molins J. Chem. Phys., 2002, 117, 5529.

[6] O. Makhotkina, J. Lieffrig, O. Jeannin, M. Fourmigué, E. Aubert, E. Espinosa Cryst.Growth Des.,

2015, 15, 3464.

[7] K. Lamberts, P. Handels, U. Englert, E. Aubert, E. Espinosa CrystEngComm, 2016, 18, 3832.

[8] M. E. Brezgunova, E. Aubert, S. Dahaoui, P. Fertey, S. Lebègue, C. Jelsch, J. G. Ángyán, E. Espinosa

Cryst. Growth Des., 2012, 12, 5373.

[9] M. E. Brezgunova, J. Lieffrig, E. Aubert, S. Dahaoui, P. Fertey, S. Lebègue, J. G. Ángyán, E. Espinosa

Cryst. Growth Des., 2013, 13, 3283.

[10] I. Mata, E. Molins, I. Alkorta, E. Espinosa J. Phys. Chem. A, 2015, 119, 183. [11] I. Alkorta, I. Mata, E. Molins, E. Espinosa Chem. Eur. J, 2016, 22, 9226.

13

Institut de Biologie Structurale, Grenoble, France. weik@ibs.fr

Kinetic X-ray crystallography permits the structural characterization of macromolecular conformational changes along a reaction pathway at the atomic level of spatial resolution. After triggering the biological reaction within a macromolecular crystal, functionally relevant conformational changes are either arrested by flash-cooling the crystal, allowing characterization of the structure by conventional cryo-crystallography (intermediate trapping), or followed in real time by time-resolved crystallography at room temperature. The temporal resolution of the latter is limited to 100 ps if carried out in the form of Laue crystallography at synchrotrons. The advent of X-ray free electron lasers (XFELs) has pushed the resolution to the sub-ps regime, allowing ultrafast changes to be studied by time-resolved serial femtosecond crystallography [1].

After reviewing the current status of the field, we will illustrate the time-resolved crystallography approach with the study of ultra-fast photoswitching in a fluorescent protein from a non-fluorescent (off) to a fluorescent (on) state further to excitation by a light flash [2]. Our consortium (see author list of [2]) has employed time-resolved serial femtosecond crystallography at an XFEL to identify the transient structure of the photoswitchable fluorescent protein rsEGFP2 in its excited state, and to observe its chromophore in a twisted conformation, midway between the stable configurations of the on and off states. This observation has been confirmed by simulations and has allowed us to rationally design a mutant with a two-fold increased photoswitching quantum yield.

[1] Colletier J-P, Schiro G., Weik. M., Time-resolved serial femtosecond crystallography, towards molecular movies of biomolecules in action. X-ray Free Electron Lasers : A Revolution in Structural

Biology., Ed. Petra Fromme, Sebastien Boutet, Mark Hunter. Springer International Publishing. 2018 pp

331 - 356

[2] Coquelle N, Sliwa M, Woodhouse J, Schirò G, Adam V, Aquila A, Barends TRM, Boutet S, Byrdin M, Carbajo S, De la Mora E, Doak RB, Feliks M, Fieschi F, Foucar L, Guillon V, Hilpert M, Hunter MS, Jakobs S, Koglin JE, Kovacsova G, Lane TJ, Lévy B, Liang M, Nass K, Ridard J, Robinson JS, Roome CM, Ruckebusch C, Seaberg M, Thepaut M, Cammarata M, Demachy I, Field M, Shoeman RL, Bourgeois D, Colletier J-P, Schlichting I, Weik M. Chromophore twisting in the excited state of a photoswitchable fluorescent protein captured by time-resolved serial femtosecond crystallography.

14

MISCA MEDAL

ABOUT CRYSTALS AND THEIR PROPERTIES

Angeles Monge

Instituto de Ciencia de Materiales. Consejo Superior de Investigaciones Científicas (ICMM-CSIC) Sor Juana Ines de la Cruz, Madrid Spain . amonge@icmm.csic.es

In this talk, Angeles Monge will show some of her contributions to the main research fields in which she has been involved, followed by recent results from her present investigation in the field of reticular chemistry: Enhancement of properties through MOFs structural design (Figure 1): materials discovery, theoretical calculations, chemical activity, and physical properties.

Figure 1. Is it possible to code and transfer selected metal ratios from MOFs to multimetal oxides with

novel, desired compositions through a simple calcination process. [1,2]

[1] Castillo-Blas, C.; de la Peña-O’Shea, V. A.; Puente-Orench, I.; de Paz, J. R.; Sáez-Puche, R.; Gutiérrez-Puebla, E.; Gándara, F.; A. Monge,. Science Advances 2017

[2] Celia Castillo-Blas, Nieves López-Salas, María C. Gutiérrez, Inés Puente-Orench, Enrique Gutiérrez-Puebla, M. Luisa Ferrer, M. Ángeles Monge, Felipe Gándara, J.Am. Chem. Soc. 2019, 141, 1766−1774.

15

MAMMI AWARD

Development and application of crystallographic methodologies

for powder diffraction

Angela Altomarea a

CNR-IC, Bari, Italy. angela.altomare@ic.cnr.it

Crystal structure solution by powder diffraction data, although limited to small molecules, is an attractive and still challenging topic. The software EXPO [1] occupies a relevant role in this field. Among its distinguishing features we mention: based on sound theoretical principles; supported by innovative methodologies; developed according to the most recent and advanced programming languages; mainly automatic; continuously improved in terms of computational and graphic performances.

EXPO is able to face arduous problems, with the aim of pushing more and more the limits of the structure solution process by powder.

The presentation will be mainly focused on some highlights of EXPO: the determination of crystal cell parameters of small proteins; the successful application of a clever procedure, based on a random approach, for extracting the structure factor moduli from the experimental diffraction pattern [2]; the crucial action of the structure model optimization step able to provide the correct solution starting from the model derived by Direct Methods, even approximate and very far from the true one [3]; the strategies, both methodological and computational, for attaining the global minimum and gaining execution time in the solution process by Simulated Annealing [4]; the effective combination of solving structure by both reciprocal and direct space method.

Examples of solution will be discussed by covering a quite large range of cases in terms of experimental conditions and structure complexity. The capacity of the current version of EXPO to increase the number of successful outcomes and expand the limits of feasibility of powder diffraction for solving crystal structures will be proved.

A quick presentation of QUALX [5] and OChemDb [6] software will be also given for pointing out the benefit of their use in the process of deep investigation of a polycrystalline material.

[1] A. Altomare, C. Cuocci, C. Giacovazzo, A. Moliterni, R. Rizzi, N. Corriero, A. Falcicchio J. Appl.

Cryst. 2013, 46, 1231.

[2]A. Altomare, C. Giacovazzo, A.G.G Moliterni, R. Rizzi J. Appl. Cryst. 2001, 34, 704.

[3] A. Altomare, C. Cuocci, A. Moliterni, R. Rizzi, N. Corriero, A. Falcicchio J. Appl. Cryst. 2017, 50, 1812.

[4] A. Altomare, N. Corriero, C. Cuocci, A. Falcicchio, A. Moliterni, R. Rizzi J. Appl. Cryst. 2018, 51, 505.

[5] A. Altomare, N. Corriero, C. Cuocci, A. Falcicchio, A. Moliterni, R. Rizzi J. Appl. Cryst. 2015, 48, 598.

[6] A. Altomare, N. Corriero, C. Cuocci, A. Falcicchio, A. Moliterni, R. Rizzi J. Appl. Cryst. 2018, 51, 1229.

16

NARDELLI AWARD

Total Scattering Methods in Reciprocal Space: Developing

Crystallographic Tools for Nanostructured and Disordered Materials

Federica Bertolotti

Dipartimento di Scienza e Alta Tecnologia and To.Sca.Lab., Università dell’Insubria, Como, Italy federica.bertolotti@uninsubria.it

Nanocrystals (NCs) represent an innovative class of materials showing highly designable and tunable properties. Their size/shape dependent physico-chemical properties provide the opportunity to develop innovative functional materials for an extremely vast range of applications.[1] In spite of this exciting scenario, an exhaustive characterization of NCs is still a challenging task.

In this field, electron microscopy techniques, i.e. transmission electron microscopy (TEM), are often employed to get information of particles’ size, shape, morphology and aspect ratio. However, these methods can provide only 2D, local information on selected particles that might not be representative of the ensemble.[2]

On the other hand, conventional powder diffraction methods based on the Rietveld-like approach are able to provide structural information on the entire volume of sample irradiated by X-ray, but they are rather inadequate in the proper characterization of NCs. Indeed, for NCs, peaks broadening in the diffraction profile is the result of the coexistence of different effects, such as reduced crystalline domains, peculiar (eventually anisotropic) morphologies, surface induced lattice strains and other type of structural or compositional defects (i.e. point or planar defects, such as dislocation or stacking faults).[3]

Total scattering (TS) methods, in particular the Debye Scattering Equation (DSE)[4] based approach treats both Bragg and diffuse scattering on equal basis and allows the modeling of the TS pattern of NCs without any assumption of periodicity and order. Since the computation operates starting from real space atomistic models, structural and microstructural information can be simultaneously derived within a unified approach.[3] The modeling of the TS pattern is then performed in reciprocal space, avoiding all the issues related to the Fourier transform of the experimental data (i.e. Fourier transform truncation errors and very poor angular resolution associated to the experimental requirements).

Moreover, the possibility of modeling both the Small- and Wide-angle regions of the TS pattern, with the DSE method, taking advantage of their complementarity in terms of length scales (from the atomic to the nanometer one), offers the opportunity of detecting sophisticate nanocrystals morphologies and disentangling defects-induced peaks broadening, from the size-induced effects.

Accordingly, this method has been successfully extensively applied to a wide-range of nanomaterials, characterized by different kind of structural distortions and defectiveness.[5]

Here, experimental and modeling aspects related to the DSE approach, along with an overview of applications, from nanosized colloidal quantum dots and perovskites up to innovative engineered nanoapatites, will be presented.

Acknowledgement. Part of this work was supported by Fondazione Cariplo, HYPATIA Project: 2016-0248.

[1] Carey, G. H.; Abdelhady, A. L.; Ning, Z.; Thon, S. M.; Bakr, O. M.; Sargent, E. H. Colloidal Quantum Dot Solar Cells. Chem. Rev. 2015, 115, 12732–12763.

[2] Liu, J.; Olds, D.; Peng, R.; Yu, L.; Foo, G. S.; Qian, S.; Keum, J.; Guiton, B. S.; Wu, Z.; Page, K., Chem. Mater.

2017, 29, 5591-5604.

[3] Bertolotti, F.; Moscheni, D.; Guagliardi, A.; Masciocchi, N. Eur J Inorg Chem 2018, 3789-3803

[4] a) Debye, P., Ann. Phys. 1915, 351, (6), 809-823; Cervellino, A.; b) Frison, R.; Bertolotti, F.; Guagliardi, J. Appl.

Cryst. 2015, 48, 2026-2032.

[5] a) Moscheni, D.; Bertolotti, F.; Piveteau, L.; Protesescu, L.; Dirin, D. N.; Kovalenko, M. V.; Cervellino, A.; Pedersen, J. S.; Masciocchi, N.; Guagliardi, A. ACS Nano 2018, 12, 12558–12570; b) Bertolotti, F.; Protesescu, L.; Kovalenko, M. V.; Yakunin, S.; Cervellino, A.; Billinge, S. J. L.; Terban, M. W.; Pedersen, J. S.; Masciocchi, N.; Guagliardi, ACS Nano 2017, 11, 3819–3831; c) Bertolotti, F.; Dirin, D. N.; Ibanez, M.; Krumeich, F.; Cervellino, A.; Frison, R.; Voznyy, O.; Sargent, E. H.; Kovalenko, M. V.; Guagliardi, A.; and Masciocchi, N. Nat Mater 2016, 15, 987–94; d) Bertolotti, F.; Moscheni, D.; Migliori, A.; Zacchini, S.; Cervellino, A.; Guagliardi, A.; Masciocchi, N. Acta

17

XAVIER SOLANS PRIZE

Ordering patterns in mullite

Paul B. Klar,a Iñigo Etxebarriab, Gotzon Madariagac a

Institute of Physics of the Czech Academy of Sciences, Prague, Czech Republic

b

Departamento de Física Aplicada II, Universidad del País Vasco UPV/EHU, Spain

b

Departamento de Física de la Materia Condensada, Universidad del País Vasco UPV/EHU, Spain paul.klar@fzu.cz

Mullite (Al4+2xSi2–2xO10–x) is a well-known material with numerous high-tech applications in

different branches including the aerospace industry. Although mullite was thoroughly investigated for decades, structural research on mullite could not establish a model that involved a fundamental understanding of the ordering phenomena in mullite, namely the distribution of oxygen vacancies and Al/Si ordering. Therefore, recent computational simulations, performed to understand the properties and applications of mullite, usually assume a random distribution of vacancies and Al/Si [1]. The objective of this presentation is to explain the fundamental ordering mechanisms in mullite, based on a combination of synchrotron single crystal diffraction experiments and first-principles calculations.

Diffraction patterns of mullite reveal a characteristic diffuse scattering alongside a set of satellite reflections. The latter requires using higher-dimensional superspace crystallography for a complete structural description. Superspace model refinements confirm that mullite is mainly disordered and the modulation is caused by a specific distribution pattern of oxygen vacancies, related to Al/Si ordering and the arrangement of tetrahedra around vacancies. However, the refinements indicate that the identified ordering patterns are present to different extents, i.e. different degrees of order exist [2]. From that, and in accordance with superspace symmetry, a completely ordered model was established, suitable for different kinds of atomistic simulations. Refined modulation functions from disordered models and from DFT calculations on ordered commensurate superstructures are in very good agreement [3]. The underlying ordering patterns establish a structural model that serves as a basis for future investigations of the properties and applications of mullite.

Figure 1. Superstructure of mullite Al4.8Si1.2O9.6 (x = 0.4) with Al/Si and vacancy ordering pattern.

[1] Schneider, H. , Fischer, R. X. and Schreuer, J. J. Am. Ceram. Soc. 2015, 98, 2948–2967 [2] Klar, P. B., Etxebarria, I. & Madariaga, G. IUCrJ. 2018, 5, 497–509.

18

BEST PhD THESIS AWARD

HIGH-PRESSURE BEHAVIOR OF MICROPOROUS MATERIALS:

CRYSTAL-FLUID INTERACTIONS AND DEFORMATION

MECHANISMS AT THE ATOMIC SCALE

DAVIDE COMBONI

Dipartimento di scienze della terra "Ardito Desio", Università degli Studi di Milano

Zeolite are crystalline, hydrated aluminosilicates characterized by a tetrahedral framework of TO4 units, connected in such a way that sub-nanometric channels and cages occur. These

structural cavities host the so-called extra-framework population, which mainly consists of alkali and alkaline-earth cations and small molecules, such as H2O

1,2

. In the last decades, the scientific community showed a rising interest on the behavior of microporous and mesoporous compounds at high-pressure conditions, and on the crystal-fluid interaction phenomena occurring at extreme conditions3,4. High-pressure experiments on synthetic zeolites may pave the way for new routes of tailoring new functional materials (made by hybrid host-guest architecture), bearing a potentially relevant technological impact5. From a geological point of view, zeolites could act as a carrier for H2O and others small molecules or for monoatomic

species (e.g., CO2, CH4, H2S, He, Ar, Kr, Xe,…), and any change of the P-induced

extra-framework population (at ambient to low/high T) can have relevant geochemical and geophysical implications6. In this experimental thesis, the high-pressure behavior and the crystal-fluid interaction at the atomic scale of a selected series of natural and synthetic zeolites (i.e., AlPO4-5, leonhardite, laumontite, phillipsite) and a zeolites-like mineral (i.e.,

armstrongite) have been investigated by means of in-situ single-crystal X-ray diffraction, using “penetrating” and “non-penetrating” pressure-transmitting fluids in a diamond anvil-cell, exploring the different crystal-fluid interaction in materials with large or small channels, and with or without extra-framework population. The experiments were conducted at the Earth Science Department of Milan (ESD-MI) and at the beamlines ID15b (at ESRF, Grenoble) and P2.02 (at DESY, Hamburg). The results obtained in the framework of this experimental thesis showed that several variables govern the sorption phenomena at high pressure, among those: the “free diameters” of the framework cavities, the chemical nature and the configuration of the extra-framework population, the partial pressure of the penetrating molecule in the fluid (if mixed with other non-penetrating molecules), the rate of P-increase, the surface/volume ratio of the crystallites and the temperature at which the experiment is conducted. P-induced phenomena at the atomic scale were described on the basis of high-quality structure refinements. Geological and technological potential implications were discussed, e.g. about the H2O load carried by laumontite, leonhardite and phillipsite in relevant geologic environments

(e.g., first km of the subducted oceanic crust, oil reservoir, …), along with the potential of synthetic and natural zeolites as energy storage materials.

1

Baerlocher, C., Mccusker, L.B., and Olson, D.H. 2007, Atlas of Zeolite frAmework types.

2_{R.T. Pabalan and F.P. Bertetti. Rev. Mineral. Geochem. 2001, 45, 453–518.} 3_{G.D. Gatta and Y. Lee Mineral. Mag. 2014, 78, 267–291.}

4

G.D. Gatta, P. Lotti and G. Tabacchi. Phys. Chem. Miner. 2018 , 45, 115–138.

5

V. Eroshenko, R. Regis, M. Soulard, J. Patarin, J. Cr. Phys. 2002, 3, 111–119.

6

19

BEST PhD THESIS AWARD

Biochemical and structural studies on urease inhibition,

a nickel-dependent virulence factor

Luca Mazzei,a Michele Cianci,b Francesco Musiani,a Stefano Benini,c Marta Palombo,a Gábor Lente,d Stefano Ciurli a

a

Dept. of Pharmacy and Biotechnology, University of Bologna (Italy)

b

Dept. of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche (Italy)

c

Bioorganic Chemistry and Bio-Crystallography Laboratory, Faculty of Science and Technology, Free University of Bolzano (Italy)

d

Dept. of General and Physical Chemistry, University of Pécs (Hungary) luca.mazzei2@unibo.it

Urease is a nickel-dependent enzyme that catalyzes the rapid hydrolysis of urea, determining an overall increase of pH and causing negative consequences for human health as well as agriculture [1]. For these reasons, the scientific community has devoted intense efforts in the last several decades for the development of efficient and specific inhibitors of urease able to counteract its negative effects [2].

In this work, X-ray protein crystallography has been applied to urease to determine the inhibition mode of several urease inhibitors: i) fluoride [3], and ii) N-butylthiophosphotriamide (NBPT) [4] directly bind to the di-nuclear metallic center in the active site. In particular, NBPT, a commercial nitrogen stabilizer extensively used in agriculture, acts as a slow-binding inhibitor of urease, undergoing an in situ hydrolysis that generates a tetrahedral moiety blocking the active site and precluding the enzyme from further substrate hydrolysis. Two other molecules, iii) benzoquinone [5] and iv) catechol [6] have been structurally proved to act as urease inhibitors by blocking the mobile flap covering the active site of the enzyme in an open state. All the results shown in this work will be useful to develop, through a structure-based drug design procedure, novel and more efficient urease inhibitors.

Figure 1. Atomic models of the active site of urease inhibited by the hydrolyzed form of NBPT (A) and

bound to catechol (B), superimposed on the final 2Fo-Fc electron density maps.

[1] M. J. Maroney, S. Ciurli, Chem. Rev. 2014, 114, 4206.

[2] L. Mazzei, F. Musiani, S. Ciurli, in The Biological Chemistry of Nickel, RSC. 2017. [3] S. Benini, M. Cianci, L. Mazzei, S. Ciurli, J. Biol. Inorg. Chem. 2014, 19, 1243. [4] L. Mazzei, M. Cianci, U. Contaldo, F. Musiani, S. Ciurli, Biochemistry 2017, 56, 5391. [5] L. Mazzei, M. Cianci, F. Musiani, S. Ciurli, Dalton Trans. 2016, 45, 5455.

[6] L. Mazzei, M. Cianci, F. Musiani, G. Lente, M. Palombo, S. Ciurli, J. Inorg. Biochem. 2017, 166, 182. B

20

BEST PhD THESIS AWARD

Electronic properties and chemical bonding in tetrazolate based

coordination polymers

S. Racioppiabc, V. Colombob, A. Sironib, M. Andrzejewskic, R. Scatenac, P. Macchicd a

Chalmers University of Technology, Department of Chemistry and Chemical engineering, Göteborg, Sweden.

b

University of Milan, Department of Chemistry, Milan, Italy

c

University of Bern, Department of Chemistry and Biochemistry, Bern, Switzerland

d

Polytechnic of Milan, Department of Chemistry Materials and Chemical Engineering, Milan, Italy racioppi@chalmers.se

Materials having dielectric constant lower than silicon dioxide (≈ 4) as interlayer insulators are nowadays necessary in modern microelectronic devices to guarantee high performance and low power consumption.[1] In order to reach lower and lower dielectric constants, the research moved to porous materials, particularly to Metal Organic-Frameworks (MOFs).[2] In this context, Metal Azolate Frameworks (MAFs)[3] are chemically and thermally more stable then classic systems based on carboxylic ligands, and so, suitable for this kind of applications. In order to investigate the performances of MAFs as low dielectric constant materials, we studied CuL∙2EtOH (L=5-(4-pyridyl)tetrazolate)[4]

, a 2-dimensional system. Susceptibility and dielectric constant, of both the solvated and evacuated systems, were measured with impedance spectroscopy on pellets and computed using Crystal17 code[5]. While high resolution x-ray diffraction experiments and Hansen&Coppens multipolar models[6] were used to rationalize the interactions in this material. Impedance spectroscopy analysis demonstrated that, CuL has an extremely low value of static dielectric constant, equal to 1.90 at 105 Hz. It was proved that the synergic combination of preferential orientation with the anisotropy of the dielectric tensor promoted the insulator character of this material when prepared as a pellet.

Further, the decoration of L with one fluorine atom (LF=5-(2-fluoro-4-pyridyl)tetrazolate) produced two new isostructural coordination polymer with coinage metal cations: AgLF and CuLF. Chemical behavior under pressure of both not-porous (AgLF, CuLF) and porous (CuL∙2EtOH) systems was investigated. In spite of being isostructural at ambient conditions, Cu(I) and Ag(I) coordination polymers behaved differently at high pressure. Indeed, an opposite attitude for metallophilic interactions was revealed and confirmed by topological analysis[7]. On the other hand, negative linear compressibility (NLC) was observed for CuL∙2EtOH, due to interactions between layers induced by compression, with a consequently increment of the network’s dimensionality.

[1] W. Volksen, R. D. Miller, G. Dubois, Chem. Rev. 2010, 110, 56–110. [2] M. Usman, S. Mendiratta, K. L. Lu, ChemElectroChem 2015, 2, 786–788.

[3] J. P. Zhang, Y. B. Zhang, J. Bin Lin, X. M. Chen, Chem. Rev. 2012, 112, 1001–1033.

[4] F. Wang, R. Yu, Q. S. Zhang, Z. G. Zhao, X. Y. Wu, Y. M. Xie, L. Qin, S. C. Chen, C. Z. Lu, J. Solid

State Chem. 2009, 182, 2555–2559.

[5] R. Dovesi, V. R. Saunders, C. Roetti, R. Orlando, C. M. Zicovich-Wilson, F. Pascale, B. Civalleri, K. Doll, N. M. Harrison, I. J. Bush, et al., 2018.

[6] P. Coppens, X-Ray Charge Densities and Chemical Bonding, Oxford University Press, New York,

1997.

21

FELLOWSHIP FOR ABROAD RESEARCH

NSD protein family: a new promising target for

epigenetic therapy of tumor diseases

Benny Danilo Belviso,a Yunpeng Shen,b Benedetta Carrozzini, a Masayo Morishita, b Eric di Luccio,b RoccoCaliandroa

a

Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Bari, Italy

b

Department of genetic engineering, Kyungpook National University, Daegu, South Korea danilo.belviso@ic.cnr.it

Epigenetics is considered a powerful weapon to fight cancer diseases, especially against the ones with poor prognostics and still incurable, such as multiple myeloma.[1] Differently from traditional chemioterapy, this therapeitic strategy is reversible, thus offering the opportunity for cancer cells to get back to physiological state. This is why proteins involved in epigenetics are today considered promising targets for cancer treatment. Among these proteins, nuclear receptor binding SET domain (NSD) proteins, a family of three histon lysine methyl transferases, are considered decisive for suppressing currently lethal cancer diseases.[2] The Institute of Crystallography and the Kyungpook National University are working together to provide structural information for NSDs, as a first step of a structure-based drug design of NSD inhibitors. By combaining Small-Angle X-ray Scattering (SAXS) and homology modeling, we obtained the first structural details regarding NSDs and new insights about NSDs stability and conformation. Based on this structural knowledge, peptido-mimetic potential NSD inhibitors have been selected by virtual screening. Moreover, an optimized protocol to express NSDs fused with T4L crystallization-chaperon has been succesfully optimized with the aim to increase crystallization chances of these crystallization-recalictrant family of proteins. Finally, the Schizosaccharomyces pombe Set7 protein, belonging to the histone-methyltransferase (HMT) family, has been characterized by X-diffraction at 2 Å resolution (PDB code 5h6z, Fig. 1).[3] Altogether, these results represent an important breakthrough in the structural study of this family of protein and pave the way for the development of NSD inhibitors.

Figure 1. Schizosaccharomyces pombe Set7 protein crystal structure

obtained at 2Å resolution (PDB code 5h6z) [1] M. Fardi, S. Solali, M.F. Haghe,Genes Dis. 2018, 5(4), 304

[2] M. Morishita, E. di Luccio, Biochim Biophys Acta, 2011, 1816(2), 158

[3] Y. Shen, D.E.H.F. Mevius, R. Caliandro, B. Carrozzini, Y. Roh, J. Kim, S. Kim, S.C. Ha, M. Morishita, E. di Luccio, Structure 2019, 27, 631

22

BEST GRADUATE THESIS AWARD

Engineering murine neuroglobin: structural and functional analysis of the

heme sliding mechanism

Ida Fredaa,b, Cécile Exertiera,b Linda Celeste Montemiglioa,b,c, Antonella Scaglionea,b,e, Gabriele Ceruttia, Giacomo Parisia,b,d, Carmelinda Savinoc, Beatrice Vallonea,b,c

a_{Dipartimento di Scienze Biochimiche “A. Rossi Fanelli”, Università di Roma “La Sapienza”, Rome, Italy} b

Istituto Pasteur - Fondazione Cenci Bolognetti, Rome, Italy,

c

Istituto di Biologia e Patologia Molecolare - CNR, Rome, Italy.

d

Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA

e

Neuroscience Initiative, CUNY Advanced Science Research Center, New York, NY, USA. ida.freda@uniroma1.it

Neuroglobin (Ngb) is a 17 kDa heme protein, predominantly expressed in the central and peripheral nervous system. It clearly seems to be involved in neuroprotection, most likely through a role in gas/redox sensing and radical scavenging, although its mechanism of action is still not fully clarified. Even though this protein displays the canonical globin fold, it only shares less than 21% of sequence identity with myoglobin [1]. In the absence of exogenous ligands, the heme iron atom in Ngb is hexacoordinated in ferrous and ferric form by two conserved histidines, His(F8)96 proximally and His(E7)64 distally, and this feature confers to the protein peculiar binding kinetics. Indeed, binding of diatomic gaseous ligands occurs upon rupture of the His64-Fe bond, and this latter event triggers the heme sliding inside a large internal cavity, as revealed by the structure of CO-bound Ngb [2]. This movement is accompanied by the reshaping of the cavity, by the motion of helices and loops, and by the conformational change of residues adjacent to the heme, such as Phe106 which is displaced to allow the heme sliding [3].

On the basis of these observations, artificial point mutants have been produced to pinpoint the major structural determinants of ligand binding regulation in murine neuroglobin. Among them, the mutant F106A was studied to probe the role of the heme sliding by analyzing the structural features and the binding kinetics of a Ngb variant with reduced hindrance at the heme proximal side [4].

[1] Burmester T, Weich B, Reinhardt S, Hankeln T. Nature. 2000, 407, 520-523.

[2] Dewilde S, Kiger L, Burmester T, Hankeln T, Baudin-Creuza V, Aerts T, Marden MC, Caubergs R, Moens L. J Biol Chem. 2001, 276, 38949.

[3] Vallone B, Nienhaus K, Matthes A, Brunori M, Nienhaus GU. Proc Natl Acad Sci USA. 2004, 101, 17351.

[4] Exertier C, Milazzo L, Freda I, Montemiglio LC, Scaglione A, Cerutti G, Parisi G, Anselmi M, Smulevich G, Savino C, Vallone B. Sci Rep. 2019, 9:5326.

23

COMMERCIAL PRESENTATIONS

Photon Counting with Mixed-mode Detectors

Vernon Smith,a Roger Dursta, Vernon Smitha, Joerg Kaercherb, Bruce Beckerb, Tobias Stuerzera a

Bruker AXS GmbH, Karlsruhe, Germany, bBruker AXS Inc, Madison, WI, USA, vernon.smith@bruker.com

Modern single-crystal X-ray diffraction relies entirely on two-dimensional pixel array detectors (PADs). Their underlying CMOS technology allows shutterless data collection which has widely eliminated experimental overhead time. Today, two different techniques are competing in the home laboratory market. HPADs have now been available for over ten years [1] and rely on being able to count individual X-ray events in the time-domain. The introduction of HPADS was a significant advance in detector technology, but several fundamental drawbacks have been extensively described in the scientific literature [2, 3].

More recently, detector developments at leading synchrotrons and at Bruker AXS have focussed attention on photon-counting using mixed-mode detection. Mixed-mode detection uses charge-integrating technology to count individual photon events in the space-domain. Mixed-mode detection retains all the benefits of the older HPAD technology but does not suffer from the same drawbacks. As a result, the reflection intensities are measured significantly more accurately [4].

Bruker AXS have introduced the first commercially available mixed-mode detector – the PHOTON III [5]. The PHOTON III series employs large monolithic sensors with no dead areas in genuine photon-counting detectors with no charge sharing or counting errors.

The technical background of mixed-mode detection will be introduced accompanied by a variety of crystallographic examples to highlight the features of the PHOTON III detectors.

Figure 1. PHOTON III Series of mixed-mode photon-counting detectors

[1] M. J. Renzi, M. W. Tate, A. Ercan, S. M. Gruner, E. Fontes, C. F. Powell, A. G. MacPhee, S. Narayanan, J. Wang and R. Cuenca, Review of Scientific Instruments , 2002, 73:3, 1621-1624.

[2] K. Mathieson, R. Bates, V. O’Shea, M.S. Passmore, M. Rahman, K.M. Smith, J. Watt, C. Whitehill,

Nuclear Instruments and Methods in Physics Research A. 2002 477, 191–197.

[3] A. Bergamaschi , R.Dinapoli, B.Henrich, I.Johnson, A.Mozzanica, X.Shi, B.Schmitt, Nuclear

Instruments and Methods in Physics Research A. 2011, 628, 238-241.

[4] F. Leonarski, S. Redford, A. Mozzanica, C. Lopez-Cuenca, E. Panepucci, K. Nass, D. Ozerov, L. Vera, V. Olieric, D. Buntschu, R. Schneider, G. Tinti, E. Froejdh, K. Diederichs, O. Bunk, B. Schmitt , M. Wang , Nature Methods, 2018, 15, 799-804.

24

Latest developments from Rigaku

Mark Benson

Rigaku Europe SE, Neu Isenburg, Germany. Mark.Benson@Rigaku.com

Performing data collections which are not only high quality but also efficient is a key requirement of many diffractometer users around the world, either to enable high throughput, or maximise data quality in a given time.

The new XtaLAB Synergy diffractometer line represent improvements in both hardware and software design. Advancements have been made not only in the microfocus sources but also in the goniometer and detector hardware. The sample environment has been completely redesigned allowing ample space for easier access or incorporation of specialist equipment. The combination of these enhancements leads to better data quality in shorter data collection times for both weakly and strongly diffracting crystals.

Ensuring the best possible use of the diffractometer hardware and the data it provides requires high performance software. The CrysAlisProsoftware package is under continual development in order to provide enhanced automation features, new options for sample screening, data collection and improvements to data processing algorithms.

25

Characterization of a few vanadate compounds using both the Aeris

benchtop and the Empyrean platform

Eugenio Casini,a Gwilherm Nénert,b a

Malvern PANalytical Italy, Via Cadore, 21, 20851 - Lissone, Italy

b

Malvern PANalytical, Lelyweg 1, 7602 EA Almelo, The Netherlands. eugenio.casini@malvernpanalytical.com

The relation between crystal structure and properties of mineral-related materials is the key for technological benefits. MalvernPanalytical is committed to provide state-of-the-art solutions for basic and advanced studies both in ambient and non-ambient conditions (temperature, pressure, humidity, etc.). The synthesis and characterization of two new vanadate related materials is presented. AgCaVO4 is a new material related to arcanite (-K2SO4). By means of laboratory

powder X-ray data, its crystal structure has been determined [1]. This compound exhibits a distorted arcanite structure, contrary what has been previously reported for AgBVO4 (B = Mg,

Cd) compounds. Furthermore we report a new larnite related vanadate NaSrVO4 exhibiting a

complex phase diagram as a function of temperature [2]. This compound is the first report for a AIBIIXVO4 chemistry exhibiting the larnite structure. This result hints that the larnite structure

can accommodate a richer chemistry that initially foreseen.

Figure 1. HT-XRD data collected on the NaSrVO4 sample.

[1] G. Nénert; Zeitschrift fuer Kristallographie,2017, 232(10), 669 [2] G. Nénert; O’Meara, P., Degen, T.; Acta. Cryst. A., 2016, 72, s62

26

The new Thermo Scientific Krios G4 Cryo-TEM and Falcon 4:

“Bringing leading technology into the standard lab and offering a road to

success for experienced and new cryo-EM user

s”.

Max Malettaa, Marc Storms, Kristian Wadel, Steve Reyntjens a

Materials and Structural Analysis, Analytical Instruments Group, Thermo Fisher Scientific Achtseweg Noord 5651 GG Eindhoven, The Netherlands.

Structural biologists have made great progress in unraveling the structures of individual proteins and protein complexes. Much of these recent results have been made using Single Particle Analysis (SPA), which has turned into a well-accepted and almost routine technique. Continuous efforts to make cryo-EM even more mature are taken by further improving its productivity (throughput) and ease-of-use.

During this talk, we will introduce the latest generation of the award-winning Krios platform including new direct electron detector which embarks experienced, as well as new users, on their continuing mission to become more productive and improve the image quality of their 3D reconstructions. Simultaneously, the adoption of cryo-EM is further facilitated through improving the system’s usability and installability.

27

MS1 - Crystallography out of Academia

Chairs: Alessia Bacchi (Univ. di Parma)

28

MS1 - KN1: Diffraction for industries, businesses and health

Miguel A. G. Aranda,a,b Angeles G. De la Torre,a Laura León-Reina,c Marta García-Matéd a_{Departamento de Química Inorgánica, Universidad de Málaga, Campus Teatinos S/N. 29071, Málaga,}

Spain. g_aranda@uma.es

b

ALBA synchrotron collaborator, Carrer de la Llum 2-26, E-08290 Barcelona, Spain

c

Servicios Centrales de Apoyo a la Investigación, Universidad de Málaga, 29071, Málaga, Spain

d

X-Ray Data Services, Pje Carlos Cano 7, 296200, Torremolinos, Málaga, Spain

Powder diffraction is widely used at, or requested by, industries. Even more, new regulations are including the use of powder diffraction and even its data treatment by the Rietveld method. Several examples will be provided.

I. The amount of respirable low-solubility dust particles in air in the workplace is undesirable and already subject to regulation(s). A key subgroup is respirable crystalline silica which if inhaled it increases the risk of developing serious silica-related diseases, including: (a) silicosis, (b) lung cancer; (c) chronic obstructive pulmonary disease; and (d) kidney disease [1]. OSHA (Occupational Safety and Health Administration of USA) Method ID-142 (2015) describes the collection of airborne respirable α-quartz and/or cristobalite in the breathing zone of personnel and the subsequent analysis by X-ray diffraction according to Method NIOSH-7500. In Spain there are related regulations: (1) MTA/MA-014/A11 by Insituto Nacional de Seguridad e Higiene en el Trabajo, INSHT, “Determinación de materia particulada (fracciones inhalable, torácica y respirable) en aire - método gravimétrico”; (2) MTA/MA-056/A06 by INSHT “Determinación de sílice libre cristalina (cuarzo, cristobalita, tridimita) en aire - Método del filtro de membrana / Difracción de rayos X”; and (3) Guía Técnica – Métodos de determinación de fracción respirable y sílice cristalina respirable” Departamento Técnico. Instituto Nacional de la Silicosis. Some details about our meticulous implementation will be provided but some specific details of our know-how will not be shared.

II. ASTM C1365 test method for cement Rietveld quantitative phase analysis validation procedure uses SRM 2686a reference material from NIST, which is a reference Portland clinker with reported elemental and mineralogical analyses. Laboratories and cement factories can implement ASTM C1365, by using the powder diffraction data of SRM 2686a collected with their X-ray equipments and employing their protocols but the output shall be within the ASTM C1365 limits. We were aware of problems for validating ASTM C1365 by several industries and we have thoroughly studied SRM 2686a using: (1) strictly monochromatic CuKα1 ‘flat

reflection geometry’; (2) strictly monochromatic MoKα1 ‘flat transmission geometry’; and (3)

synchrotron radiation ‘rotating capillary transmission geometry’. Our results [2] indicate that belite in SRM 2686a is composed of two polymorphs (- and α’H-) that must be included in the

analyses. The use of a unique phase for describing belite and inadequate peak shape modelling explain the problems found for implementing ASTM C1365. Polymorphism matters.

III. ALBA synchrotron and DRX unit of SCAI of University of Malaga have provided powder diffraction analyses for different industries and fields. Some examples will be sketched.

Acknowledgements. Partly supported by MinCIU research grants, BIA2014-57658 & BIA2017-82391-R Data accessibility. SRM 2686a powder diffraction data are deposited at Zenodo and they can be freely

downloaded (doi: 10.5281/zenodo.1318500). Many data are confidential (they are subjected to NDA). [1] https://www.osha.gov/dsg/topics/silicacrystalline/

29

MS1 - KN2: Crystalline form suitable for inhalation in drug discovery

Irene Bassanettia

a_{Chiesi Farmaceutici – Corp.Precl. R&D Analytics & Early Formulations Dept., Parma, Italy}

i.bassanetti@chiesi.com

Inhalatory drug administration is a promising alternative route for chronic treatment of pulmonary diseases as it minimizes systemic side effects: in fact, it allows to localize and target the delivery with minimum systemic exposure. A successful pulmonary administration requires a harmonic interaction between the API, the excipient, the inhaler device, and the patient. Three main inhalation systems are widely used for pulmonary drugs and are clinically equivalent: nebulizers and pressurized Metered Dose Inhalers (pMDIs) are based on solution/suspension formulations, while Dry Powder Inhalers (DPIs) generate aerosol directly from solid API mixed with solid excipients or carriers. Especially for the latter the complete solid state characterization of API is the key role for an efficient deposition in the lungs: packing, size, morphology, excipient compatibility and stability could affect the aerodynamic performance and the efficacy of the drug.[1] For the formers, instead, solid state properties are essential for API solubility and primarily bioavailability: polymorphism, solvate and salt formation can have a profound impact on solubility rate thus influencing both absorption and the pharmacokinetic. As a result, the crystallization screening (polymorphs, salts and co-crystals screening) should start in earlier phases of drug discovery during lead selection or lead optimization, as a part of the Screening Cascade of tests for the selection of Candidate Drugs (CD). Moreover, due to the type of delivery chosen many constraints are introduced. Solvents used must be safe (Class III); the counterions for salts are preferably limited to ones already known for inhalation; coformers must be selected not only following the crystal engineering laws but must be either inactive ingredients or selected co-drugs tolerated in inhalation and with a synergistic effect on the targeted disease[2].

In addition, also the particle engineering technologies should be considered in the choice of a lead form for developability. To reach low airways, to be absorbed, the crystalline drug should be micronized (1-5 µm) prior to blending, using a jet mill or similar device with the risk of change polymorphic form, melting or amorphous formation due to the heating evolved during the process. Then, the crystal size, habit, shape and surface of micronized material need to be fully controlled after blending to be sure the micronized material results compatible with the chosen excipients.

The challenges to face for selecting a CD are tough: here different case studies are shown to demonstrate how crystallography is essential also for researchers out of academia.

[1Patton, J. S., & Byron, P. R. (2007). Inhaling medicines: delivering drugs to the body through the lungs.

Nature Reviews Drug Discovery, 6(1), 67-74.

[2] Huang, L.F.&Tong, WQ. (2004). Impact of solid-state properties on developability assessment of drug candidates. Advanced Drug Delivery Reviews, 56(3), 321-334.

[3] Selby, M. D., de Koning, P. D., & Roberts, D. F. (2011). A perspective on synthetic and solid-form enablement of inhalation candidates. Future medicinal chemistry, 3(13), 1679-1701.

30

MS1 - O1: Determining the concentration of diamond powder deposited on

a textile yarn: a multitechnique approach

S. Ciattini1,L. Chelazzi1,

1

Center of Structural Crystallography (CRIST). University of Florence. Via della Lastruccia 3, 50019 Sesto Fiorenitno (Firenze), Italy, samuele.ciattini@unifi.it

The aim of our study was the development of an analytical method to determine the amount of diamond powder deposited on a textile yarn. This analytical need arises to certify the concentration of diamond itself in textile fabric. Due to the fact that diamond textile yarn had to be used to produce luxury and high fashion manufactures, the certification was an absolute need in the marketing of such products that are proposed with a remarkable price to the final users. The production line of the diamond wire was developed by a company of Prato (Tuscany, Italy) textile area.

The analytical issues could be pointed out as follow:

1) verification of the presence of the diamond powder on the final fabric and as consequence on the textile yarn,

2) determination of the linear concentration of diamond on the textile yarn,

3) verification of the homogeneity of the product sample, i.e. the concentration should be constant throughout the whole process production.

CRIST (Crystallography Center - Università di Firenze) is an academic facility with a wide range of available X-ray instrumentations, most of them dedicated to X-ray diffraction analysis[1]. Then, the first idea was to verify the presence of diamond in the final fabric through an X-ray diffraction analysis. But for the quantitive analisys a multi tecniques approach, like XRF-WD spectrometry, X-ray microtomografy[2] and of course XRD-PD, had to be used.

Figure 1. 3D reconstruction of a textile yarn used in micro tomography analysis with different transparency

References:

[1] Bruker-AXS, DIFFRACPlus TOPAS: TOPAS 4.2 Technical Reference, Bruker-AXS GmbH, Karlsruhe, Germany (2008)

[2] Feldkamp L.A., Davis L.C., Kress J.W. Practical cone-beam algorithm. J Opt Soc Am. A1:612-619, 1984

31

MS2 - In situ and in operando studies of systems

structural evolution

Chairs:

Javier Gonzales-Plata (Univ. de La Laguna)