Publications

54. Remke, S. C., T. H. Bürgin, L. Ludvíková, D. Heger, O. S. Wenger, U. von Gunten, and S. Canonica (2022), Photochemical oxidation of phenols and anilines mediated by phenoxyl radicals in aqueous solution, Water Research, 118095, doi: https://doi.org/10.1016/j.watres.2022.118095.

53. Závacká, K., V. Neděla, E. Tihlaříková, P. Šabacká, J. Maxa, and D. Heger (2021), ESEM Methodology for the Study of Ice Samples at Environmentally Relevant Subzero Temperatures: “Subzero ESEM”, Microscopy and Microanalysis, 1-14, doi: 10.1017/S1431927621013854.

52. Vesely, L., B. Susrisweta, and D. Heger (2021), Making good's buffers good for freezing: The acidity changes and their elimination via mixing with sodium phosphate, Int J Pharm, 593, 120128, doi: 10.1016/j.ijpharm.2020.120128.

• Protons are the smallest chemical entities and thus also the fastest reacting compounds. Their concentrations, measured in solutions by pH, therefore embody a very important indicator and strongly influence the stability of all the compounds present, including biochemical ones, such as proteins. Acidity is not well defined in the frozen state; however, protons influence the compounds in that state too. As freezing and lyophilization are extensively performed on the laboratory and industrial scales, we intend to characterize the frozen systems in their access to protons. In this article, we examined three Good’s buffers to reveal the freezing-induced basification and neutralized the process by adding a phosphate buffer. The output lies in a useful guideline for freezing with these buffers.

51. Vetrakova, L., V. Nedela, J. Runstuk, E. Tihlarikova, D. Heger, and E. Shalaev (2020), Dynamical in-situ observation of the lyophilization and vacuum-drying processes of a model biopharmaceutical system by an environmental scanning electron microscope, International journal of pharmaceutics, 119448, doi: 10.1016/j.ijpharm.2020.119448.

• The article characterizes the sublimation residua of bovine serum albumin (BSA), a good model of other proteins, in relation to variously frozen samples. The residua embody a freeze-concentrated solution on which we examined the structures of freeze-dried and vacuum-dried pharmaceutical solutions via an ESEM. Compared to the common practice, where only the morphology of the final dry product is inspected, we monitored the entire drying process. We showed that the morphology and mechanical stability of a lyophile markedly depend on the freezing method, namely, the freezing rate and directionality, even when the drying conditions are identical. Based on the obtained results, we hypothesised that the freezing directionality and rate embody the key parameters to determine the resulting lyophile morphology. Unexpectedly, and contrary to the underlying assumptions proposed in previous SEM studies of freeze-dried materials, we demonstrated that the morphology can be significantly altered during the ice sublimation as compared to the frozen state, even at temperatures well below the collapse temperature (Tc). Therefore, studying a final freeze-dried material might not suffice to yield relevant data on the morphology of the ice crystals formed during the freezing step.

50. Sršeň, Š., J. Sita, P. Slavíček, V. Ladányi, and D. Heger (2020), Limits of the Nuclear Ensemble Method for Electronic Spectra Simulations: Temperature Dependence of the (E)-Azobenzene Spectrum, Journal of Chemical Theory and Computation, 16(10), 6428-6438, doi: 10.1021/acs.jctc.0c00579.

• The article discusses a very unusual and unexpected thermal behaviour of the spectrum of (E)-azobenzene (trans-azobenzene). In a previous publication, we showed that the compound is problematic to keep pure, as it isomerizes readily under the slightest exposure to light. The compound therefore has to be handled in a dark environment, and this task was performed by Vít Ladányi, who also reproducibly acquired the spectra of pure (E)-azobenzene at a range of temperatures. When subtracted from one another, the spectra exhibited “vibration-like structures” and changes in the relative intensities for the individual absorption bands (Fig. 5). At the final stage, we were unsure about how to explain the observations and utilized gladly the assistance by Petr Slavíček, who helped us with the calculations.

49. Ondrušková, G., L. Veselý, J. Zezula, J. Bachler, T. Loerting, and D. Heger (2020), Using Excimeric Fluorescence to Study How the Cooling Rate Determines the Behavior of Naphthalenes in Freeze-Concentrated Solutions: Vitrification and Crystallization, The Journal of Physical Chemistry B, 124(46), 10556-10566, doi: 10.1021/acs.jpcb.0c07817.

• The fast and slow cooling of aqueous solutions of organic compounds pose the question of how much the cooling rate can change the resulting state. In this paper we use the fluorescence of naphthalene and methylnaphthalene to reveal that the answer reads a lot: Slow cooling allows the compounds to crystallize, while fast cooling does so to a much lesser extent, as is inferable intuitively. We nevertheless reached somewhat farther, establishing that the concentrated organics mixed with residual water can form a glass which appears plastic in fast cooling but not in slow cooling.

48. Leresche, F., L. Ludvikova, D. Heger, U. von Gunten, and S. Canonica (2020), Quenching of an Aniline Radical Cation by Dissolved Organic Matter and Phenols: A Laser Flash Photolysis Study, Environ Sci Technol, 54(23), 15057-15065, doi: 10.1021/acs.est.0c05230.

• Reactivity in natural waters is complex and thus difficult to describe. This line of projects, carefully designed by Silvio Canonica from Switz EAWAG, aims to describe the photo-induced redox reactivity. We provide here the time- resolved kinetics, together with the equipment and knowledge required for the interpretation.

47. Vetráková, Ľ., V. Neděla, J. Runštuk, and D. Heger (2019), The morphology of ice and liquid brine in an environmental scanning electron microscope: a study of the freezing methods, The Cryosphere, 13(9), 2385-2405, doi: 10.5194/tc-13-2385-2019.

46. Leresche, F., L. Ludvikova, D. Heger, P. Klan, U. von Gunten, and S. Canonica (2019), Laser flash photolysis study of the photoinduced oxidation of 4-(dimethylamino)benzonitrile (DMABN), Photochem Photobiol Sci, 18(2), 534-545, doi: 10.1039/c8pp00519b.

45. Kim, K., J. Ju, B. Kim, H. Y. Chung, L. u. Vetráková, D. Heger, A. Saiz-Lopez, W. Choi, and J. Kim (2019), Nitrite-Induced Activation of Iodate into Molecular Iodine in Frozen Solution, Environmental Science & Technology, 53(9), 4892-4900, doi: 10.1021/acs.est.8b06638.

44. Imrichova, K., L. Vesely, T. M. Gasser, T. Loerting, V. Nedela, and D. Heger (2019), Vitrification and increase of basicity in between ice Ih crystals in rapidly frozen dilute NaCl aqueous solutions, J Chem Phys, 151(1), 014503, doi: 10.1063/1.5100852.

• Freezing the solution of common salt (NaCl) we found interesting phenomena: fast cooling makes part of the freeze concentrated solution vitrified and acidity is shifting during the processes.

43. Heger, D., A. J. Eugene, S. R. Parkin, and M. I. Guzman (2019), Crystal structure of zymonic acid and a redetermination of its precursor, pyruvic acid, Acta Crystallographica Section E Crystallographic Communications, 75(6), 858-862, doi: 10.1107/s2056989019007072.

42. Choi, Y., H.-I. Yoon, C. Lee, L. u. Vetráková, D. Heger, K. Kim, and J. Kim (2018), Activation of Periodate by Freezing for the Degradation of Aqueous Organic Pollutants, Environmental Science & Technology, 52(9), 5378-5385, doi: 10.1021/acs.est.8b00281.

41. Leresche, F., Ludvikova, L., Heger, D., Klán, P., von Gunten, U., and Canonica, S.: Laser flash photolysis study of the photoinduced oxidation of 4-(dimethylamino)benzonitrile (DMABN), Photochemical & Photobiological Sciences, 10.1039/C8PP00519B, 2018.

• In this project, let by Silvio Canonica, we helped with the laser flash photolysis and kinetic analysis. It is shown, that direct and triplet sensitized photolysis both leads to oxidized form of aromatic amine which reacts further on.

40. Ondrušková, G., Krausko, J., Stern, J. N., Hauptmann, A., Loerting, T., and Heger, D.: Distinct Speciation of Naphthalene Vapor Deposited on Ice Surfaces at 253 or 77 K: Formation of Submicrometer-Sized Crystals or an Amorphous Layer, The Journal of Physical Chemistry C, 122, 11945-11953, 10.1021/acs.jpcc.8b03972, 2018.

• By fluorescence analysis of naphthalene we found amorphous layer and very small crystals on the ice surfaces upon the conditions of vapour deposition at 77 and 253 K, respectively. I think this finding is of great importance, as it shows, that besides the dissolved organic matter the crystallites should be considered for the atmospheric relevance.

39. V. Ladanyi, P. Dvorak, J. Al Anshori, L. Vetrakova, J. Wirz and D. Heger, Azobenzene photoisomerization quantum yields in methanol redetermined, Photochemical & Photobiological Sciences, 2017, 16, 1757-1761.

38. L. Vetrakova, V. Ladanyi, J. Al Anshori, P. Dvorak, J. Wirz and D. Heger, The absorption spectrum of cis-azobenzene, Photochemical & Photobiological Sciences, 2017, 16, 1749-1756.

• Azobenzene is a very elemental molecule; we synthesized it in the basic organic labs. First described in 1834, with its cis isomer characterized in 1937, azobenzene has found multiple applications, most notably as a molecular switch and an actinometer (a substance to measure the amount of light incident on the sample). We were, however, surprised to identify major inconsistency when using two actinometers: azobenzene and ferrioxalate. The absorption spectra of azobenzene’s individual forms turned out to be mutually contaminated; we therefore separated them via careful chemical treatment and "smart" mathematical minimization. The quantum yields then had to be redetermined accordingly.

37. Ľ. Vetráková, V. Vykoukal and D. Heger, Comparing the acidities of aqueous, frozen, and freeze-dried phosphate buwers: Is there a “pH memory” ewect?, International Journal of Pharmaceutics, 2017, 530, 316-325.

• We demonstrate in this paper that the pH jump occurs predominantly within the freezing step and can be masked by the subsequent sublimation in the lyophilization process. Thus, the pH change should be assesed at both stages of the sample stabilization (after freezing and after freeze-drying).

36. Ju, J.; Kim, J.; Vetráková, Ľ.; Seo, J.; Heger, D.; Lee, C.; Yoon, H.-I.; Kim, K.; Kim, J. Journal of Hazardous Materials 2017, 329, 330.

35. Fiala, T.; Ludvíková, L.; Heger, D.; Švec, J.; Slanina, T.; Vetráková, L. u.; Babiak, M.; Nečas, M.; Kulhánek, P.; Klán, P.; Sindelar, V. J. Am. Chem. Soc. 2017, 139, 2597.

34. Yang, X.; Neděla, V.; Runštuk, J.; Ondrušková, G.; Krausko, J.; Vetráková, Ľ.; Heger, D. Atmos. Chem. Phys. 2017, 17, 6291.

• We have investigated frost flowers grown from salty water (Radio broadcast, Press release).

33. Ludvikova, L.; Fris, P.; Heger, D.; Sebej, P.; Wirz, J.; Klan, P. Photochemistry of Rose Bengal in Water and Acetonitrile: A Comprehensive Kinetic Analysis. Physical Chemistry Chemical Physics 2016, , 18, 16266.

32. Krausková, Ľ.; Procházková, J.; Klašková, M.; Filipová, L.; Chaloupková, R.; Malý, S.; Damborský, J.; Heger, D. Suppression of Protein Inactivation During Freezing by Minimizing Ph Changes Using Ionic Cryoprotectants. International Journal of Pharmaceutics 2016, 509, 41-49.

31. Krausko, J.; Ondrušková, G.; Heger, D., Comment on “Photolysis of Polycyclic Aromatic Hydrocarbons on Water and Ice Surfaces” and on “Nonchromophoric Organic Matter Suppresses Polycyclic Aromatic Hydrocarbon Photolysis in Ice and at Ice Surfaces”. The Journal of Physical Chemistry A 2015, 119 (43), 10761-10763.

30. Bownik, I.; Šebej, P.; Literák, J.; Heger, D.; Šimek, Z.; Givens, R. S.; Klán, P., 4-Hydroxyphenacyl Ammonium Salts: A Photoremovable Protecting Group for Amines in Aqueous Solutions. The Journal of Organic Chemistry 2015, 80 (19), 9713-9721.

29. Krausko, J.; Malongwe, J. K. E.; Bičanová, G.; Klán, P.; Nachtigallová, D.; Heger, D. Spectroscopic Properties of Naphthalene on the Surface of Ice Grains Revisited: A Combined Experimental–Computational Approach. The Journal of Physical Chemistry A 2015, 119, 8565-8578.

28. Krausko, J.; Runštuk, J.; Neděla, V.; Klán, P.; Heger, D., Observation of a Brine Layer on an Ice Surface with an Environmental Scanning Electron Microscope at Higher Pressures and Temperatures. Langmuir 2014, 30, 5441-5447.

27. Kania, R.; Malongwe, J. K. E.; Nachtigallová, D.; Krausko, J.; Gladich, I.; Roeselová, M.; Heger, D.; Klán, P., Spectroscopic Properties of Benzene at the Air–Ice Interface: A Combined Experimental–Computational Approach. The Journal of Physical Chemistry A 2014, 118, 7535-7547.

26. Solomek, T.; Heger, D.; Ngoy, B. P.; Givens, R. S.; Klan, P. The Pivotal Role of Oxyallyl Diradicals in Photo-Favorskii Rearrangements: Transient Spectroscopic and Computational Studies. J. Am. Chem. Soc. 2013, 135, 15209-15215.

25. Kammath, V. B.; Solomek, T.; Ngoy, B. P.; Heger, D.; Klan, P.; Rubina, M.; Givens, R. S. A Photo-Favorskii Ring Contraction Reaction: The Ewect of Ring Size. Journal of Organic Chemistry 2013, 78, 1718-1729.

24. Kammath, V.B., et al., A Photo-Favorskii Ring Contraction Reaction: The Ewect of Ring Size. The Journal of Organic Chemistry, 2012.

23. Klicova, L., et al., Adiabatic Triplet State Tautomerization of p-Hydroxyacetophenone in Aqueous Solution. Journal of Physical Chemistry A, 2012. 116(11): p. 2935-2944.

22. Walsh, Z., et al., Polymerisation and surface modification of methacrylate monoliths in polyimide channels and polyimide coated capillaries using 660 nm light emitting diodes. Journal of Chromatography A, 2011. 1218(20): p. 2954-2962.

21. Veetil, A.T., et al., Photochemistry of S-Phenacyl Xanthates. Journal of Organic Chemistry, 2011. 76(20): p. 8232-8242.

20. Roubal, Z., et al. The design of high-impedance and high-voltage input amplifier for measurement of electropotentials on solidliquid phase boundary. 2011. Marrakesh.

19. Heger, D., et al., Self-Organization of 1-Methylnaphthalene on the Surface of Artificial Snow Grains: A Combined ExperimentalComputational Approach. Journal of Physical Chemistry A, 2011. 115(41): p. 11412-11422.

18. Givens, R.S., et al., p-Hydroxyphenacyl photoremovable protecting groups - Robust photochemistry despite substituent diversity. Canadian Journal of Chemistry-Revue Canadienne De Chimie, 2011. 89(3): p. 364-384.

17. Kammari, L., et al., Orthogonal Photocleavage of a Monochromophoric Linker. Journal of the American Chemical Society, 2010. 132(33): p. 11431-11433.

16. Stensrud, K., et al., Competing Pathways in the Photo-Favorskii Rearrangement and Release of Esters: Studies on Fluorinated pHydroxyphenacyl-Caged GABA and Glutamate Phototriggers. Journal of Organic Chemistry, 2009. 74(15): p. 5219-5227.

15. Khan, M.S.A., et al., Remarkable Salt Ewect on Stability of Supramolecular Complex between Modified Cueurbit[6]uril and Methylviologen in Aqueous Media. Journal of Physical Chemistry B, 2009. 113(32): p. 11054-11057.

14. Walsh, Z., et al., Photoinitiated polymerisation of monolithic stationary phases in polyimide coated capillaries using visible region LEDs. Chemical Communications, 2008(48): p. 6504-6506.

13. Stensrud, K.F., et al., Fluorinated photoremovable protecting groups: the influence of fluoro substituents on the photo-Favorskii rearrangement. Photochemical & Photobiological Sciences, 2008. 7(5): p. 614-624.

12. Givens, R.S., et al., The photo-Favorskii reaction of p-hydroxyphenacyl compounds is initiated by water-assisted, adiabatic extrusion of a triplet biradical. Journal of the American Chemical Society, 2008. 130(11): p. 3307-3309.

11. Heger, D. and P. Klan, Interactions of organic molecules at grain boundaries in ice: A solvatochromic analysis. Journal of Photochemistry and Photobiology a-Chemistry, 2007. 187(2-3): p. 275-284.

10. Born, R., et al., Photochromism of phenoxynaphthacenequinones: diabatic or adiabatic phenyl group transfer? Photochemical & Photobiological Sciences, 2007. 6(5): p. 552-559.

9. Plistil, L., et al., Photochemistry of 2-alkoxymethyl-5-methylphenacyl chloride and benzoate. Journal of Organic Chemistry, 2006. 71(21): p. 8050-8058.

8. Heger, D., J. Klanova, and P. Klan, Enhanced protonation of cresol red in acidic aqueous solutions caused by freezing. Journal of Physical Chemistry B, 2006. 110(3): p. 1277-1287.

7. Heger, D., J. Jirkovsky, and P. Klan, Aggregation of methylene blue in frozen aqueous solutions studied by absorption spectroscopy. Journal of Physical Chemistry A, 2005. 109(30): p. 6702-6709.

6. Zabadal, M., et al., Intramolecular triplet-triplet energy transfer in short flexible bichromophoric amino acids, dipeptides and carboxylic acid diester. Collection of Czechoslovak Chemical Communications, 2004. 69(4): p. 776-796.

5. Zabadal, M., et al., N-(1-Naphthylacetyl)glycine phenacyl ester and phenacyl (1-naphthylacetoxy)acetate. Acta Crystallographica Section C-Crystal Structure Communications, 2003. 59: p. O77-O79.

4. Literak, J., et al., Photochemistry of alkyl aryl ketones on alumina, silica-gel and water ice surfaces. Journal of Photochemistry and Photobiology a-Chemistry, 2003. 154(2-3): p. 155-159.

3. Klanova, J., et al., Comparison of the ewects of UV, H2O2/UV and gamma- irradiation processes on frozen and liquid water solutions of monochlorophenols. Photochemical & Photobiological Sciences, 2003. 2(10): p. 1023-1031.

2. Klan, P., et al., Temperature-sensitive photochemical aromatic substitution on 4-nitroanisole. Photochemical & Photobiological Sciences, 2002. 1(12): p. 1012-1016.

1. Klan, P., M. Zabadal, and D. Heger, 2,5-dimethylphenacyl as a new photoreleasable protecting group for carboxylic acids. Organic Letters, 2000. 2(11): p. 1569-1571.

Reviews

2. Bartels-Rausch, T.; ., et al., A review of air–ice chemical and physical interactions (AICI): liquids, quasi-liquids, and solids in snow. Atmos. Chem. Phys. 2014, 14, 1587-1633.

1. McNeill, V.F., et al., Organics in environmental ices: sources, chemistry, and impacts. Atmos. Chem. Phys., 2012. 12: p. 9653-9678.

Book chapter

2. Heger, D., Govindarajan, R., Lu, E., Ewing, S., Lay-Fortenbery, A., Yuan, X., . . . Shalaev, E. (2023). Beyond pH: Acid/Base Relationships in Frozen and Freeze-Dried Pharmaceuticals. In F. Jameel (Ed.), Principles and Practices of Lyophilization in Product Development and Manufacturing (pp. 39-61). Cham: Springer International Publishing.

• This review documents that looking back may bring new interpretations and ideas.

1. Klán, P. and D. Heger (2021). Spectroscopy and photochemistry of organic compounds in ice. Photochemistry: Volume 48, The Royal Society of Chemistry. 48: 423-444.