Head of the Department of physical and chemical research: Dr. of Chemistry Alexander B. Rozhenko Head of the Department
Dr. of Chemistry Alexander B. Rozhenko

The Department of Physical and Chemical Research (original name - Department of Molecular Structure and Spectroscopy) was founded in 1968 by Doctor of Chemistry, Professor Yu.P. Yegorov. From 1995 to 2016, the department was headed by Candidate of Chemical Sciences M.Y. Povolotsky. Currently, the head of the department is Dr. of Chemistry A.B. Rozhenko.

The main scientific directions of the department are the study of the molecular and electronic structure and reactivity of organic and organoelement compounds. For this purpose, the methods of X-ray diffraction studies (XRD), nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), high-performance liquid chromatography (HPLC) are used, and quantum-chemical calculations are also carried out. To perform elemental analysis of chemical compounds, the department includes an analytical laboratory, headed by N.Y. Kuznetsova.

In the Institute of Organic Chemistry of the NAS of Ukraine, NMR spectroscopy has traditionally always been and remains the main spectral method for studying chemical reaction products. The department operates two Varian Mercury+ NMR spectrometers. This allows the department's specialists to record and interpret one- and two-dimensional NMR spectra for synthesized organic and organoelement compounds at once on four different magnetically active 1H, 13C, 19F and 31P nuclei. The method is indispensable for monitoring the proceeding chemical reactions and kinetic studies, rapid identification of synthesis products and, finally, for establishing the degree of their purity. If necessary, qualified employees of the department record solid-state NMR spectra, as well as electron paramagnetic resonance (EPR) spectra in the corresponding Collective Use Centers of the NAS of Ukraine.

Since 2006, the Center for Collective Use «X-ray Single Crystal Diffractometry» operates as the part of the department. For X-ray diffraction studies of chemical compounds, the Bruker SMART APEX II single crystal X-ray diffractometer is used. Experienced specialists of the Center are able to determine the structure not only for crystalline samples, but sometimes even for compounds that are liquids under normal conditions. In addition to determining the molecular structure, the X-ray diffraction method allows studying such phenomena as polymorphism and phase transitions in crystals, to investigate the conformational features of compounds, as well as the subtle effects of their spatial and electronic structure.

Modern chemistry cannot be imagined without computer modeling. The employees of the department perform theoretical studies of the electronic and spatial structure, reactivity of organic and organoelement compounds, as well as mechanisms of chemical reactions at the modern level, using modern quantum-chemical methods. The use of modern molecular modeling software packages (TURBOMOLE, ORCA, GROMACS, etc.) allows you to conduct a wide range of theoretical studies. These are molecular mechanics/dynamics, docking, hybrid methods QM/MM (DFT/molecular mechanics) and, finally, precise quantum-chemical calculations of the spatial and electronic structure of molecules, intermolecular interactions, spectral properties and mechanisms of chemical reactions, in vacuum, in solutions and in crystals. IR spectroscopy methods are used to study the reactivity of organic and organoelement compounds and their ability to form complexes, as well as the kinetics of chemical processes in the flow mode. High-performance liquid chromatography allows studying the ability of supramolecular ligands to perform the functions of effective means for drug delivery.

In recent years, flow reactors for the safe generation of diazomethane and a flow photoreactor have been installed and actively used in the laboratories of the Department of Physico-chemical Research. The reactors are designed for the synthesis of building blocks for medicinal chemistry in multigram quantities.

Articles
  1. da Silva Mesquita, R.; Kyrylchuk, A.; Grafova, I.; Kliukovskyi, D.; Bezdudnyy, A.; Rozhenko, A.; Tadei, W. P.; Leskelä, M.; Grafov, A. Synthesis Molecular Docking Studies, and Larvicidal Activity Evaluation of New Fluorinated Neonicotinoids against Anopheles Darlingi Larvae PLoS One 2020, 15 (2), e0227811
  2. Blahun, O. P.; Rozhenko, A. B.; Rusanov, E.; Zhersh, S.; Tolmachev, A. A.; Volochnyuk, D. M.; Grygorenko, O. O Twisting and Turning the Sulfonamide Bond: A Synthetic, Quantum Chemical, and Crystallographic Study J. Org. Chem. 2020, 85 (8), 5288–5299
  3. Yesypenko, O. A.; Osipova, A. O.; Tribrat, O. O.; Kravchenko, S. O.; Usachov, O. M.; Dyakonenko, V. V.; Ryabitskii, A. B.; Pirozhenko, V. V.; Shishkina, S. V.; Rozhenko, A. B.; Kalchenko, V. I. Synthesis and Enantiorecognition Properties of Stereoisomeres of Inherently Chiral Propyloxy-Octyloxy-Calix[4]Arene Acetic Acids Tetrahedron 2021, 80, 131894
  4. Marchenko, A.; Koidan, G.; Hurieva, A.; Shvydenko, K.; Rozhenko, A. B.; Rusanov, E. B.; Kyrylchuk, A. A.; Kostyuk, A. Latent Nucleophilic Carbenes J. Org. Chem. 2022, 87 (1), 373–385
  5. Holovach, S.; Melnykov, K. P.; Skreminskiy, A.; Herasymchuk, M.; Tavlui, O.; Aloshyn, D.; Borysko, P.; Rozhenko, A. B.; Ryabukhin, S. V.; Volochnyuk, D. M.; Grygorenko, O. O. Effect of Gem ‐Difluorination on the Key Physicochemical Properties Relevant to Medicinal Chemistry: The Case of Functionalized Cycloalkanes Chem. – A Eur. J. 2022, 28 (19), e202200331
  6. Kvasha, D. A.; Deviatkin, A.; Poturai, A. S.; Nosik, P. S.; Kyrylchuk, A. A.; Suikov, S.; Rozhenko, A. B.; Volochnyuk, D. M.; Grygorenko, O. O. Metal-Free C–H Difluoromethylation of Imidazoles with the Ruppert–Prakash Reagent J. Org. Chem. 2023, 88 (1), 163–171
  7. Kalchenko, O. I.; Rozhenko, A. B.; Cherenok, S. O.; Selikhova, A. I.; Suikov, S. Y.; Kyrylchuk, A. A.; Kalchenko, V. I. Complexation of Water-Soluble Phosphorylated Calixarenes with Uracils. Stability Constants and DFT Study of the Supramolecular Complexes J. Incl. Phenom. Macrocycl. Chem. 2023, 103 (9–10), 369–383
  8. Koidan, G.; Hurieva, A. N.; Rozhenko, A. B.; Manthe, U.; Spengler, T.; Zahorulko, S.; Shvydenko, T.; Kostyuk, A. Latent Carbene in Diaminomethylation of Benzenes: Mechanism and Practical Application J. Org. Chem. 2023, 88 (11), 7233–7244
  9. Koidan, G.; Zahorulko, S.; Hurieva, A.; Shvydenko, T.; Rusanov, E. B.; Rozhenko, A. B.; Manthe, U.; Kostyuk, A. Straightforward Synthesis of Halopyridine Aldehydes via Diaminomethylation Chem. – A Eur. J. 2023, 29 (55), e202301675
  10. Pendiukh, V. V.; Yakovleva, H. V.; Stadniy, I. A.; Pashenko, A. E.; Rusanov, E. B.; Grabovaya, N. V.; Kolotilov, S. V.; Rozhenko, A. B.; Ryabukhin, S. V.; Volochnyuk, D. M. Practical Synthetic Method for Amino Acid-Derived Diazoketones Shelf-Stable Reagents for Organic Synthesis Org. Process Res. Dev. 2024, 28 (1), 165–176

Flow reactor for diazomethane generation

The reactor is shown in Figure 1. The reactor consists of three main units: pump unit A, reaction unit B and membrane separator C. Pump unit A is equipped with a controller that allows switching between pure solvent and substrate modes and built-in flow pressure regulators; with a reaction column with external cooling and backpressure regulators with precise adjustment of the operating mode and liquid pressure gauges. For additional safety, reaction unit B is closed with a removable polycarbonate housing. Membrane separator C is equipped with laminated PTFE membrane filters with a porosity of 1.0 microns. Diazomethane and substrate solutions are fed through rubber septa and a pressure regulator D into a cooled batch reactor E, equipped with a magnetic stirrer, thermometer and argon inlet with a pressure of 2 atm.

Appearance of a flow-through installation for the generation of diazomethane Fig. 1. Appearance of a flow-through installation for the generation of diazomethane

The pump unit A is assembled on the basis of syringe pumps 1, controlled via a touch screen 2 (Fig. 2). The design features of the unit allow for continuous supply of reagents without delays and additional calibration. Valves 3 are controlled via the same touch screen 2, they provide switching between reagent solutions and solvents for washing. The installation implements a three-channel system with independent control of the inlet pressure and monitoring using electronic pressure gauges 4, which perform an emergency stop if the threshold pressure exceeds the permissible value.

Pump unit of the reactor Fig. 2. Pump unit of the reactor

Reagents and solvents are supplied from glass bottles. (Fig. 3). Each bottle is equipped with a lid with two valves, where one valve is used to supply the solution, the other serves to enter the inert gas. In order to avoid “clogging” of the working space, the cooler 1, as well as bottles with reagents and solvents 2 are placed under the fume hood. The reagent streams enter the reaction column 2 through the mixer 1 (Fig. 2). For better mixing, the decomposition of methylnitrosourea (MNU) is carried out in a borosilicate glass tube filled with polypropylene beads and cooled to 4 °C with water from an external thermostat. The total volume of the reaction unit is 50 ml, which, according to the results of the experiment, is sufficient to ensure complete decomposition of MNU. From the outlet of the reaction unit, the two-phase mixture enters the membrane separator 3, where the stream is separated into aqueous waste and an organic solution of CH2N2 (Fig. 4). Both streams pass through the pressure control unit. Backpressure regulators 1 allow you to optimize the pressure gradient on the separator membrane, which provides more efficient phase separation. Precise adjustment of excess pressures on each stream in the range from 0 to 2 atm (manometers 3) completely eliminates factors that can affect phase separation, such as the composition and concentration of solutions, temperature and ratio of input streams. This setting allows you to use the reactor for a wider range of reactions with a choice of a diverse set of solvents. The target solution is fed through tube 4 for further use (Fig. 5).

Cooling unit and reagent supply Fig. 3. Cooling unit (1) and reagent supply (2)
Reaction block with membrane separator Fig. 4. Reaction block with membrane separator
Pressure control unit Fig. 5. Pressure control unit

Flow photoreactor UOSlab® FlowReactor UF365/450

In 2020, within the framework of the implementation of the NFDU project 0120U104008, the semi-industrial photochemical reactor UOSlab® FlowReactor UF365/450 (Scheme 2) was purchased, installed and put into operation. It is designed to carry out photochemical processes in solutions with the additional possibility of using gases as reagents and for the safe production of products of such reactions in multigram quantities. This device is the most modern equipment of this type in Ukraine. It consists of a photochemical unit equipped with a pump unit and control components, and an external thermostat that controls the temperature inside the reaction spiral. In addition, an additional external thermostat is provided for cooling the LED unit, which is used in this photoreactor as a irradiation source. The undoubted advantage of this scheme over other similar devices is that the intense irradiation of LEDs at a certain moment acts only on a small amount of substrate solution for a sufficiently long time, necessary for the solution to pass through the transparent tubes of the device. This ensures a high degree of conversion, safety and continuity of the process, which is so important for photochemical processes on a semi-industrial scale. In addition, it allows for reliable and convenient control of the process temperature, the choice of its flow rate and the overall productivity of the reactor. Owing to the block diagram, this photoreactor is suitable for easy replacement of the light source with a similar block generating light with a different wavelength.

Principle diagram of a photoreactor Scheme 2. Principle diagram of a photoreactor
Structure of photoreactor

The appearance of the UOSlab® FlowReactor UF365/450 flow photoreactor is shown in Figure 1. It consists of three main components: reaction block A, in which the substrate solution is irradiated with light of the required wavelength; pump block B, controlled by an external controller and equipped with an additional module for metered gas supply; and high-precision circulation thermostat C, which provides temperature control of the reaction zone. All control of the external and internal components of the reactor is carried out via a sensor controller D. The system is equipped with a back pressure regulator. Temperature measurement is carried out at the outlet of the photoreaction block. For additional safety, the front transparent panel of the reactor is covered with a film that absorbs radiation.

External view and main components of the assembled photoreactor UOSlab® FlowReactor UF365/450 Figure. 1. External view and main components of the assembled photoreactor UOSlab® FlowReactor UF365/450: A: reaction module; B: pumping unit; C: high-precision circulation thermostat TC-85\250 UOSlab®; D: touch controller.

Pump block B includes syringe pumps (1) (Fig. 2), controlled by the controller via the touch screen D. The design features of the block allow for continuous reagent flow without time delay and the need for calibration. The tap, controlled via the screen D, provides switching between reagent solutions and washing solvents. The block implements a single-channel system with independent control and pressure control in the flow via an electronic pressure gauge (4) for emergency stop when the threshold pressure is exceeded to avoid possible emergency situations. The pump block is also equipped with a back pressure regulator (5) and a high-precision gas dispenser (6) with the possibility of metered addition of gaseous reagents to the substrate solution.

Photoreaction block Figure. 2. Photoreaction block 1: syringe pumps; 2: block for life and control of LED lamps; 3: taps for mixing between reagent dispensers and clean dispensers for washing the installation; 4: electronic pressure gauge; 5: regulator of the gate vice; 6: gas-like dispenser.

The photoreaction unit is shown in Figure 3. In the lower part there is a double polypropylene spiral (7), the lower turns of which are hidden in the housing connected to the thermostat. The upper turns are under a layer of special glass and placed on a heat exchange plate. In the upper part there is an LED panel (8), which provides intensive irradiation of the spiral. The panel includes two blocks, each of the blocks is separately connected to its own control unit (Figure 2, 2), which allows you to vary the radiation power of the LEDs in a wide range. The LED unit is equipped with a cooling system for the LEDs and temperature control of the reaction solution. The control system, in turn, provides for emergency shutdown of the LEDs both in case of overheating and in case of overcooling of the latter (overcooling is dangerous, primarily due to the appearance of unwanted condensate on the electronic boards of the LED unit). The LED panel is designed to be quickly replaced with a similar panel with a different wavelength. A viewing window is provided for visual control of the process. For safety reasons, when the cover of the photoreaction module is opened, the LED panels are automatically turned off.

Light block in open view Figure. 3. Light block in open view: 7 – double polypropylene spiral for breaking the substrate; 8 – light-emitting diode panel