Denis A. Rychkov

Crystallographic education in the 21st century

Methods and outcomes for teaching crystallography in graduate, post-graduate and secondary school environments are presented. This is an extended report based on the ideas presented in the MS92 Microsymposium at the IUCr 23rd Congress and General Assembly in Montreal.

A new polymorph of metacetamol

Metacetamol is a structural isomer of the widely used drug paracetamol and is being considered as a promising alternative to the latter because of its lower toxicity. Due to the importance of the well-known polymorphism of paracetamol, an investigation of the polymorphism of metacetamol was successfully undertaken. A new polymorph of metacetamol has been discovered and extensively characterised using a variety of analytical techniques (IR- and Raman spectroscopy, UV-visible optical spectroscopy, X-ray powder and single-crystal diffraction, TGA and DSC). A procedure for the reliable and reproducible preparation of the new polymorph is described. Its properties and crystal structure are compared with those of the previously known polymorph, as well as with those of paracetamol.

A new structure of a serotonin salt: Comparison and conformational analysis of all known serotonin complexes

Four serotonin salt structures (serotonin adipate, C10H13N2O(+)·C6H9O4(-), is a previously unknown structure) were analysed to understand the influence of the anion on serotonin conformation. Hydrogen bonding alone favours a flat conformation, whereas additional stacking interactions between ions may possibly account for the nonplanar conformation. Since molecular conformation, stability and biological activity are interrelated, one can consider influencing the chemical and biological properties of serotonin by selecting an appropriate counter-ion for salt formation.

Effect of pressure on two polymorphs of tolazamide: why no interconversion?

Two polymorphs of tolazamide, N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide, a sulfonylurea anti-diabetic drug, have different densities and molecular packings. Polymorph II converts into polymorph I in the solid state on heating or via recrystallization if solvent-assisted. The effect of pressure on the two forms and the possibility of a transformation to a denser form on compression have been studied. No phase transitions have been observed in either of the forms in a pentane–isopentane mixture (when no recrystallization is possible). Polymorph II recrystallized partly into a denser polymorph I in methanol at 0.1 GPa, but the transformation stopped at an early stage. Solid state DFT calculations of the two forms as well as conformational landscape investigation in the gas phase were used to rationalize this result. The anisotropic pressure-induced strain of the two polymorphs has been compared in relation to changes in the hydrogen bond geometry and the behavior of stacking interactions.

Structure-forming units of amino acid maleates. Case study of l-valinium hydrogen maleate

A new salt of L-valinium hydrogen maleate was used as an example to study structure-forming units in amino acid maleates. This compound was crystallized, its structure solved from single-crystal X-ray diffraction data, and the phase purity of the bulk powder sample confirmed by X-ray powder diffraction and FT-IR spectra. The stability of the new salt was analyzed using density functional theory and PIXEL calculations with focus on the C(2)2(12) structure-forming crystallographic motif. This motif was of particular interest as it is common for almost all maleates. The exceptionally high ability of maleic acid to form salts with various amino acids was rationalized.

Spin Selectivity in Chiral Linked Systems

This work has shown spin selectivity in electron transfer (ET) of diastereomers of (R,S)-naproxen-(S)-N-methylpyrrolidine and (R,S)-naproxen-(S)-tryptophan dyads. Photoinduced ET in these dyads is interesting because of the still unexplained phenomenon of stereoselectivity in the drug activity of enantiomers. The chemically induced dynamic nuclear polarization (CIDNP) enhancement coefficients of (R,S)-diastereomers are double those of the (S,S)-analogue. These facts are also interesting because spin effects are among the most sensitive, even to small changes in spin and molecular dynamics of paramagnetic particles. Therefore, CIDNP reflects the difference in magnetoresonance parameters (hyperfine interaction constants (HFIs), g-factor difference) and lifetimes of the paramagnetic forms of (R,S)- and (S,S)-diastereomers. The difference in HFI values for diastereomers has been confirmed by a comparison of CIDNP experimental enhancement coefficients with those calculated. Additionally, the dependence of the CIDNP enhancement coefficients on diastereomer concentration has been observed for the naproxen-N-methylpyrrolidine dyad. This has been explained by the participation of ET in homo-(R,S-R,S or S,S-S,S) and hetero-(R,S-S,S) dimers of dyads. In this case, the effectivity of ET, and consequently, CIDNP, is supposed to be different for (R,S)- and (S,S)-homodimers, heterodimers, and monomers. The possibility of dyad dimer formation has been demonstrated by using high-resolution X-ray and NMR spectroscopy techniques.

Teaching in a Secondary School: Crystal Growth and Basics of Crystallography

Nowadays, secondary education provides a broad variety of different compulsory courses giving a solid basis for further student’s progress at the university. However, there is an opinion that in this system we are losing the sense of adventures, discoveries and research. Now the main question is if we can efficiently combine compulsory subjects and open classrooms in order to support students in their self-realization needs and provoke interest in mundane school subjects. The educational course for pupils «Crystal Growth – from School Desk to Leading Scientific Research» began several years ago with close cooperation between Novosibirsk State University, the Institute of Solid State Chemistry and Mechanochemistry SB RAS and School #162 of Novosibirsk. The aim of the course is to provide further education in Chemistry and Crystallography via laboratory work and lectures, complementing the standard school program. We provide a targeted syllabus for students from 7 to 17 years old, covering related scientific topics starting from crystal symmetry to the basics of physical chemistry. Through close communication and interaction, pupils develop skills in growing crystals, paying particular attention to obtaining large single crystals of different substances. During the course, pupils crystallize more than 15 different substances using at least 5 different methods and their modifications. At the end of every year, the students are given the opportunity to carry out a personal project, calling on the new knowledge they have obtained from the course. Thus we can assume that an efficient program was developed and realized to support personal ideas and research for school students, based on compulsory subjects and modern experimental techniques. The work was supported by the grant of Dmitry Zimin Fund “Dynasty” “ ntertaining Science for pupils” NoDP-55/13, Development Program of University Student Association, NSU, App. No2012-PSO-225, City Hall grant for young scientists.

Serotonin in different compounds: crystallographic and computational insight

Biologically active substances are in the focus of pharmaceutical and chemical research. Serotonin, one of the most common neurotransmitters, is widely studied in relation to its effect on humans from cellular to neurological levels. Although serotonin plays a key role in some biological processes, its chemistry and crystallography are not sufficiently understood. The aim of the present study was to crystallize serotonin adipate and creatinine sulfate monohydrate, determine their crystal structures, and analyze them in a comparison with other previously known serotonin crystal structures. Special attention was paid to the interrelation between the molecular conformation and crystalline environment. This issue was addressed using crystallographic and computational chemistry (DFT-D, MD) approaches. In our research was shown that the crystal structure of the creatinine sulfate complex significantly differs from what was previously determined. The conformation of serotonin in the new structure differs from serotonin conformations in all other known complexes, as well as from the most stable conformation, predicted by the adiabatic conformational analysis using quantum chemical calculations (DFT, MP) in different phases. This work has explicitly shown the influence of different interactions on serotonin molecular conformation in the crystalline state, described from a crystallographic and theoretical point of view. It has been previously demonstrated that salt formation in the presence of different anions produces variation in pharmacological, therapeutic and physic-chemical properties. This study has shown that alterations of the anion affects the molecular geometry of the bioactive substance and invite further investigation to rationalize the geometry changes. The work was supported by the RFBR Grants No14-0331866, 13-03-92704, Russian Ministry of Science and Education and RAS, Siberian Supercomputer Center SB RAS Integration Grant No130, Edinburgh Compute and Data Facility

The experience of teaching solid-state chemistry in a secondary school. Example 1 – isomorphism of alums

Three years ago we started a special program in Secondary School No162 in Novosibirsk in order to increase the interest of pupils (grades 9-11) in natural sciences. This educational course titled “Crystal Growth – from School Desk to Leading Scientific Research” includes the fundamental of solid state chemistry and contains two parts: (i) lectures to introduce the pupils to the subject of solid state chemistry and crystallography and (ii) experimental work where pupils learn crystallisation techniques, study the physicochemical properties of the solid state and grow crystals of various substances. Throughout the programme we do not dwell on the complexity of crystallography but aim to show how to grow beautiful colored crystals with perfect shape. With this in mind, the main purpose of this program is to capture the interest of the pupils. It is important to present all information in a popular way and communicate with the pupils at their level; thats why all teachers on our course are students and postgraduate students from the department of solid state chemistry at Novosibirsk State University. At the end of the year we offer children the opportunity to perform a final research project and present their results at the school section of the International Scientific Student Conference (ISSC) held annually in Novosibirsk.

The experience of teaching solid state chemistry in a secondary school. Example 2 – growing crystals of pure metallic copper

The educational course for pupils «Crystal Growth – from School Desk to Leading Scientific Research¬ was started several years ago in close cooperation between Novosibirsk State University, the Institute of Solid State Chemistry and Mechanochemistry SB RAS and School #162 of Novosibirsk. The idea for the course is to provide further education in Chemistry and Crystallography via laboratory work and lectures, complementing the standard school programme. We provide a targeted syllabus for students from 5th form to 11th form (i.e. the last year of secondary school), covering many aspects of related science starting from crystal symmetry to the basics of physical chemistry. Through close communication and interaction, pupils develop skills in different methods of growing crystals, paying particular attention to obtaining large monocrystals of different substances. In terms of the course, pupils crystallize more than 15 different substances with at least 5 different methods and their modifications. At the end of every year, the students are given the opportunity to carry out a project, calling on the new knowledge they have obtained from the course. Such a work was done this year by Dmitry Chudakov – a 9 th