Pub Date : 2025-07-01DOI: 10.1107/S2052252525004968
Richard Dronskowski
Combining improved diffraction methods, modeling approaches and advanced computations allows for a detailed understanding of atomic thermal motions in crystals. Thus, the Topical Review by Hoser & Madsen [(2025). IUCrJ12, 421–434] covers the Debye–Waller factor, the importance of anisotropic displacement parameters, and the interplay of experiment and theory to accurately capture collective atomic vibrations in molecular crystals.
{"title":"Everything you always wanted to know about the Debye–Waller factor but were afraid to ask","authors":"Richard Dronskowski","doi":"10.1107/S2052252525004968","DOIUrl":"10.1107/S2052252525004968","url":null,"abstract":"<div><div>Combining improved diffraction methods, modeling approaches and advanced computations allows for a detailed understanding of atomic thermal motions in crystals. Thus, the Topical Review by Hoser & Madsen [(2025). <em>IUCrJ</em><strong>12</strong>, 421–434] covers the Debye–Waller factor, the importance of anisotropic displacement parameters, and the interplay of experiment and theory to accurately capture collective atomic vibrations in molecular crystals.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 4","pages":"Pages 417-418"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1107/S2052252525003355
Andrej Hlinčík , Tadeáš Fülöp , Peter Herich , Jozef Kožíšek , Karol Lušpai , Lukáš Bučinský
The refinement flexibility of the Hansen–Coppens multipole model is tested on DFT calculated structure factors for the tetrakis(μ-acetato)diaquadicopper model system. The Cu scattering factor performs the best of all the options tried for most of the monitored parameters despite the Cu2+ nature of the complex studied. The Hansen–Coppens model performs similarly well when comparing deviations among computational chemistry methods.
In this study, the flexibility of the multipole Hansen–Coppens (HC) model refinement is investigated on calculated structure factors from a DFT reference for the tetrakis(μ-acetato)diaquadicopper model system (CCDC reference 1811668). The effect of the resolution [sin(θ)/λ], the Cu scattering factor, the inclusion of anisotropic displacement parameters and the positions of the atoms in the refinement are considered in terms of statistical error analysis, residual and deformation density maps, Atoms In Molecules parameters, d-orbital populations, and others. The choice of the neutral Cu scattering factor in the HC refinement is found to give the most satisfactory results for most of the monitored parameters, despite the formal Cu2+ nature of copper in the studied complex. In order to put the difference between the HC model and the reference DFT (BLYP functional) results on the right scale, several computational chemistry methods (B3LYP, Hartree–Fock, Møller–Plesset perturbation theory and Coupled Clusters Singles and Doubles) were compared with the chosen DFT reference. Differences in the magnitudes of the structure factors and AIM parameters are presented, including considerations of relativistic effects and periodic boundary conditions, i.e. a comparison of a molecular crystal calculation versus an isolated molecule in the crystal.
{"title":"On the flexibility of the multipole model refinement. A DFT benchmark study of the tetrakis(μ-acetato)diaquadicopper model system","authors":"Andrej Hlinčík , Tadeáš Fülöp , Peter Herich , Jozef Kožíšek , Karol Lušpai , Lukáš Bučinský","doi":"10.1107/S2052252525003355","DOIUrl":"10.1107/S2052252525003355","url":null,"abstract":"<div><div>The refinement flexibility of the Hansen–Coppens multipole model is tested on DFT calculated structure factors for the tetrakis(μ-acetato)diaquadicopper model system. The Cu scattering factor performs the best of all the options tried for most of the monitored parameters despite the Cu<sup>2+</sup> nature of the complex studied. The Hansen–Coppens model performs similarly well when comparing deviations among computational chemistry methods.</div></div><div><div>In this study, the flexibility of the multipole Hansen–Coppens (HC) model refinement is investigated on calculated structure factors from a DFT reference for the tetrakis(μ-acetato)diaquadicopper model system (CCDC reference 1811668). The effect of the resolution [sin(θ)/λ], the Cu scattering factor, the inclusion of anisotropic displacement parameters and the positions of the atoms in the refinement are considered in terms of statistical error analysis, residual and deformation density maps, Atoms In Molecules parameters, <em>d</em>-orbital populations, and others. The choice of the neutral Cu scattering factor in the HC refinement is found to give the most satisfactory results for most of the monitored parameters, despite the formal Cu<sup>2+</sup> nature of copper in the studied complex. In order to put the difference between the HC model and the reference DFT (BLYP functional) results on the right scale, several computational chemistry methods (B3LYP, Hartree–Fock, Møller–Plesset perturbation theory and Coupled Clusters Singles and Doubles) were compared with the chosen DFT reference. Differences in the magnitudes of the structure factors and AIM parameters are presented, including considerations of relativistic effects and periodic boundary conditions, <em>i.e.</em> a comparison of a molecular crystal calculation versus an isolated molecule in the crystal.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 4","pages":"Pages 444-461"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1107/S2052252525005196
Johannes Elferich , Marek Kaminek , Lingli Kong , Adolfo Odriozola , Wanda Kukulski , Benoît Zuber , Nikolaus Grigorieff
Vitreous sectioning (CEMOVIS) is an alternative to FIB milling for generating thin samples suitable for cryo-EM imaging. We show that CEMOVIS samples preserve the high-resolution structural details of macromolecular complexes such as the 60S ribosome, despite the visible macroscopic damage visible in the samples.
Cryo-electron microscopy can be used to image cells and tissue at high resolution. To ensure electron transparency, the sample thickness must not exceed 500 nm. Focused-ion-beam (FIB) milling has become the standard method for preparing thin samples (lamellae); however, the material removed by the milling process is lost, the imageable area is usually limited to a few square micrometres and the surface layers sustain damage from the ion beam. We have examined cryo-electron microscopy of vitreous sections (CEMOVIS), a technique based on cutting thin sections with a knife, as an alternative to FIB milling. Vitreous sections also sustain damage, including compression, shearing and cracks. However, samples can be sectioned in series, producing many orders of magnitude more imageable area compared to lamellae, making CEMOVIS an alternative to FIB milling with distinct advantages. Using two-dimensional template matching on images of vitreous sections of Saccharomyces cerevisiae cells, we reconstructed the 60S ribosomal subunit at near-atomic resolution, demonstrating that, in many regions of the sections, the molecular structure of these subunits is largely intact, comparable to FIB-milled lamellae.
{"title":"In situ high-resolution cryo-EM reconstructions from CEMOVIS","authors":"Johannes Elferich , Marek Kaminek , Lingli Kong , Adolfo Odriozola , Wanda Kukulski , Benoît Zuber , Nikolaus Grigorieff","doi":"10.1107/S2052252525005196","DOIUrl":"10.1107/S2052252525005196","url":null,"abstract":"<div><div>Vitreous sectioning (CEMOVIS) is an alternative to FIB milling for generating thin samples suitable for cryo-EM imaging. We show that CEMOVIS samples preserve the high-resolution structural details of macromolecular complexes such as the 60S ribosome, despite the visible macroscopic damage visible in the samples.</div></div><div><div>Cryo-electron microscopy can be used to image cells and tissue at high resolution. To ensure electron transparency, the sample thickness must not exceed 500 nm. Focused-ion-beam (FIB) milling has become the standard method for preparing thin samples (lamellae); however, the material removed by the milling process is lost, the imageable area is usually limited to a few square micrometres and the surface layers sustain damage from the ion beam. We have examined <em>c</em>ryo-<em>e</em>lectron <em>m</em>icroscopy <em>o</em>f <em>vi</em>treous <em>s</em>ections (CEMOVIS), a technique based on cutting thin sections with a knife, as an alternative to FIB milling. Vitreous sections also sustain damage, including compression, shearing and cracks. However, samples can be sectioned in series, producing many orders of magnitude more imageable area compared to lamellae, making CEMOVIS an alternative to FIB milling with distinct advantages. Using two-dimensional template matching on images of vitreous sections of <em>Saccharomyces cerevisiae</em> cells, we reconstructed the 60S ribosomal subunit at near-atomic resolution, demonstrating that, in many regions of the sections, the molecular structure of these subunits is largely intact, comparable to FIB-milled lamellae.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 4","pages":"Pages 502-510"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1107/S2052252525005706
Akinobu Niozu
Crystallization is a fundamental non-equilibrium process in materials science, yet its early transient states remain difficult to probe experimentally. Möller et al. [(2025). IUCrJ12, 462–471] use femtosecond X-ray scattering and X-ray cross-correlation analysis to reveal the structural evolution of defect-containing crystals forming in a supercooled noble-gas liquid.
{"title":"Femtosecond X-rays illuminate disordered states during the early stages of crystallization","authors":"Akinobu Niozu","doi":"10.1107/S2052252525005706","DOIUrl":"10.1107/S2052252525005706","url":null,"abstract":"<div><div>Crystallization is a fundamental non-equilibrium process in materials science, yet its early transient states remain difficult to probe experimentally. Möller <em>et al.</em> [(2025). <em>IUCrJ</em><strong>12</strong>, 462–471] use femtosecond X-ray scattering and X-ray cross-correlation analysis to reveal the structural evolution of defect-containing crystals forming in a supercooled noble-gas liquid.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 4","pages":"Pages 419-420"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1107/S2052252525004543
Birger Dittrich , Rok Breznikar , Gianluca Santarossa , Pamela Whitfield , Henrik Moebitz
Single-crystal X-ray structures measured at around 20 K to high resolution were refined with structure-specific restraints from quantum chemical molecule-in-cluster and full-periodic computations, which permits benchmarking levels of theory of varying sophistication. Restraints can then ‘augment’ low-quality crystal structures, with other possible applications.
There is a need for fast, efficient and accurate solid-state structure optimization for imprecise crystal structures (‘augmentation’) for subsequent property prediction in the pharmaceutical industry. Crystal structures from single-crystal X-ray, 3D electron or powder diffraction are widely available but require augmentation to the same quality level for comparative studies. Properties can be best calculated when the level of theory is alike and the accuracy, as well as the precision, are high. Moreover, the size of molecules and the complexity of structures encountered in pharmaceutical research are increasing. Efficient procedures are thus required that can also treat structures with disorder and several molecules in the asymmetric unit of the unit cell. Hence, we investigated whether ‘molecule-in-cluster’ (MIC) computations [Dittrich et al. (2020). CrystEngComm22, 7420–7431] can reach the accuracy of full-periodic (FP) computations. Selected quantum mechanical methods are assessed. The evaluation criterion is how well the structures of 22 very low temperature high-quality structures are reproduced. Computational efficiency is also considered. A novel approach to evaluating the accuracy of quantum mechanical predictions is enforcing computed structure-specific restraints in crystallographic least-squares refinements. To complement this approach, root mean square Cartesian displacements of computed and experimental structures were also compared. Analysis shows that (a) MIC DFT-D computations in a quantum mechanics/molecular mechanics (QM:MM) framework provide improved restraints and coordinates over earlier MIC GFN2-xTB computations, (b) increasing QM basis-set size in MIC QM:MM does not systematically improve computations, and (c) the choice of DFT functional is less important than the choice of the basis set. Overall, MIC computations are an accurate and computationally efficient tool for solid-state structure optimization that can match FP computations to augment experimental structures.
制药行业需要对不精确的晶体结构（“增强”）进行快速、高效和准确的固态结构优化，以便进行后续的性能预测。单晶x射线、三维电子或粉末衍射的晶体结构广泛可用，但需要提高到相同的质量水平以进行比较研究。当理论水平相当，准确度和精密度都很高时，可以最好地计算出性质。此外，在药物研究中遇到的分子的大小和结构的复杂性也在增加。因此，需要有效的程序来处理无序结构和单位细胞的不对称单元中的几个分子。因此，我们研究了“分子簇”（MIC）计算是否[Dittrich et al.(2020)]。CrystEngComm 22, 7420-7431]可以达到全周期（FP）计算的精度。评估选定的量子力学方法。评价标准是22个极低温高质量结构的结构再现程度。计算效率也被考虑在内。一种评估量子力学预测准确性的新方法是在晶体学最小二乘改进中强制执行计算结构特异性约束。为了补充这种方法，还比较了计算结构和实验结构的均方根笛卡尔位移。分析表明：(a)在量子力学/分子力学（QM:MM）框架下的MIC DFT- d计算比早期的MIC GFN2-xTB计算提供了更好的约束和坐标，(b)在MIC QM:MM中增加QM基集的大小并没有系统地改善计算，(c) DFT泛函的选择不如基集的选择重要。总体而言，MIC计算是一种精确且计算效率高的固态结构优化工具，可以与FP计算相匹配，以增强实验结构。
{"title":"Benchmarking quantum chemical methods with X-ray structures via structure-specific restraints","authors":"Birger Dittrich , Rok Breznikar , Gianluca Santarossa , Pamela Whitfield , Henrik Moebitz","doi":"10.1107/S2052252525004543","DOIUrl":"10.1107/S2052252525004543","url":null,"abstract":"<div><div>Single-crystal X-ray structures measured at around 20 K to high resolution were refined with structure-specific restraints from quantum chemical molecule-in-cluster and full-periodic computations, which permits benchmarking levels of theory of varying sophistication. Restraints can then ‘augment’ low-quality crystal structures, with other possible applications.</div></div><div><div>There is a need for fast, efficient and accurate solid-state structure optimization for imprecise crystal structures (‘augmentation’) for subsequent property prediction in the pharmaceutical industry. Crystal structures from single-crystal X-ray, 3D electron or powder diffraction are widely available but require augmentation to the same quality level for comparative studies. Properties can be best calculated when the level of theory is alike and the accuracy, as well as the precision, are high. Moreover, the size of molecules and the complexity of structures encountered in pharmaceutical research are increasing. Efficient procedures are thus required that can also treat structures with disorder and several molecules in the asymmetric unit of the unit cell. Hence, we investigated whether ‘molecule-in-cluster’ (MIC) computations [Dittrich <em>et al.</em> (2020). <em>CrystEngComm</em><strong>22</strong>, 7420–7431] can reach the accuracy of full-periodic (FP) computations. Selected quantum mechanical methods are assessed. The evaluation criterion is how well the structures of 22 very low temperature high-quality structures are reproduced. Computational efficiency is also considered. A novel approach to evaluating the accuracy of quantum mechanical predictions is enforcing computed structure-specific restraints in crystallographic least-squares refinements. To complement this approach, root mean square Cartesian displacements of computed and experimental structures were also compared. Analysis shows that (<em>a</em>) MIC DFT-D computations in a quantum mechanics/molecular mechanics (QM:MM) framework provide improved restraints and coordinates over earlier MIC GFN2-xTB computations, (<em>b</em>) increasing QM basis-set size in MIC QM:MM does not systematically improve computations, and (<em>c</em>) the choice of DFT functional is less important than the choice of the basis set. Overall, MIC computations are an accurate and computationally efficient tool for solid-state structure optimization that can match FP computations to augment experimental structures.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 4","pages":"Pages 472-487"},"PeriodicalIF":3.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1107/S2052252525002660
Lewis J. Williams , Amy J. Thompson , Philipp Dijkstal , Martin Appleby , Greta Assmann , Florian S. N. Dworkowski , Nicole Hiller , Chia-Ying Huang , Tom Mason , Samuel Perrett , Eduard Prat , Didier Voulot , Bill Pedrini , John H. Beale , Michael A. Hough , Jonathan A. R. Worrall , Robin L. Owen
Varied pulse-duration and pulse-intensity serial femtosecond crystallography data do not show significant signs of radiation damage under typical experimental conditions.
Serial femtosecond crystallography (SFX) exploits extremely brief X-ray free-electron laser pulses to obtain diffraction data before destruction of the crystal. However, during the pulse X-ray-induced site-specific radiation damage can occur, leading to electronic state and/or structural changes. Here, we present a systematic exploration of the effect of single-pulse duration and energy (and consequently different dose rates) on site-specific radiation damage under typical SFX room-temperature experimental conditions. For the first time in SFX we directly measured the photon pulse duration, varying from less than 10 fs to more than 50 fs, and used three pulse energies to probe in-pulse damage in two radiation-sensitive proteins: the iron-heme peroxidase DtpAa and the disulfide-rich thaumatin. While difference-map features arising from radiation damage are observed, they do not lead to significant change in refined atomic coordinates or key bond lengths. Our work thus provides experimental verification that average atomic coordinates are not significantly perturbed by radiation damage in typical SFX experiments.
{"title":"Damage before destruction? X-ray-induced changes in single-pulse serial femtosecond crystallography","authors":"Lewis J. Williams , Amy J. Thompson , Philipp Dijkstal , Martin Appleby , Greta Assmann , Florian S. N. Dworkowski , Nicole Hiller , Chia-Ying Huang , Tom Mason , Samuel Perrett , Eduard Prat , Didier Voulot , Bill Pedrini , John H. Beale , Michael A. Hough , Jonathan A. R. Worrall , Robin L. Owen","doi":"10.1107/S2052252525002660","DOIUrl":"10.1107/S2052252525002660","url":null,"abstract":"<div><div>Varied pulse-duration and pulse-intensity serial femtosecond crystallography data do not show significant signs of radiation damage under typical experimental conditions.</div></div><div><div>Serial femtosecond crystallography (SFX) exploits extremely brief X-ray free-electron laser pulses to obtain diffraction data before destruction of the crystal. However, during the pulse X-ray-induced site-specific radiation damage can occur, leading to electronic state and/or structural changes. Here, we present a systematic exploration of the effect of single-pulse duration and energy (and consequently different dose rates) on site-specific radiation damage under typical SFX room-temperature experimental conditions. For the first time in SFX we directly measured the photon pulse duration, varying from less than 10 fs to more than 50 fs, and used three pulse energies to probe in-pulse damage in two radiation-sensitive proteins: the iron-heme peroxidase DtpAa and the disulfide-rich thaumatin. While difference-map features arising from radiation damage are observed, they do not lead to significant change in refined atomic coordinates or key bond lengths. Our work thus provides experimental verification that average atomic coordinates are not significantly perturbed by radiation damage in typical SFX experiments.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 3","pages":"Pages 358-371"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1107/S2052252525003653
Dominik Oberthür
Microcrystals are transforming structural biology by enabling high-resolution structures and time-resolved insights from samples once deemed too small. This commentary highlights recent advances in microfocus X-ray and MicroED methods, emphasizing their growing role as powerful and complementary tools in modern macromolecular crystallography.
{"title":"Microcrystals in structural biology: small samples, big insights","authors":"Dominik Oberthür","doi":"10.1107/S2052252525003653","DOIUrl":"10.1107/S2052252525003653","url":null,"abstract":"<div><div>Microcrystals are transforming structural biology by enabling high-resolution structures and time-resolved insights from samples once deemed too small. This commentary highlights recent advances in microfocus X-ray and MicroED methods, emphasizing their growing role as powerful and complementary tools in modern macromolecular crystallography.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 3","pages":"Pages 259-261"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1107/S2052252525002210
Szymon Grabowski , Klaudia Nowakowska , Helena Butkiewicz , Anna Hoser , Aleksandra Wesełucha-Birczyńska , Tomasz Seidler , Paulina Moskal , Marlena Gryl
This study reveals how additives and microwave radiation influence the crystallization of new tyramine polymorphs and their cocrystallization with barbital. The findings provide insights into polymorph stability and offer potential applications in molecular encapsulation and optical materials.
Polymorphism – the ability of a compound to exist in multiple crystalline forms – needs to be carefully considered in the design of functional materials, particularly in the context of cocrystallization. Tyramine, a biogenic amine, is a promising candidate for polymorph exploration due to its conformational flexibility and ability to form salts. In this study, we investigate the crystallization of tyramine polymorphs using additives and microwave-assisted techniques. Our findings reveal the formation of a new tyramine polymorph and two distinct salts, highlighting the impact of microwave radiation and additive-driven crystallization on polymorph stability and molecular encapsulation. The study demonstrates that the triclinic tyramine polymorph (T2) is thermodynamically more stable due to its lower electronic energy, whereas the monoclinic form (T1) features slightly stronger intermolecular interactions. Over time, in solution, crystals of barbital–tyramine salts (C1 and C2) begin to form, providing an opportunity to assess structural evolution. Optical properties calculations show significant maximum linear birefringence values (0.164 and 0.255) for two polymorphs of tyramine, whereas for C1, this value decreases to 0.095.
{"title":"Additive-driven microwave crystallization of tyramine polymorphs and salts: a quantum crystallography perspective","authors":"Szymon Grabowski , Klaudia Nowakowska , Helena Butkiewicz , Anna Hoser , Aleksandra Wesełucha-Birczyńska , Tomasz Seidler , Paulina Moskal , Marlena Gryl","doi":"10.1107/S2052252525002210","DOIUrl":"10.1107/S2052252525002210","url":null,"abstract":"<div><div>This study reveals how additives and microwave radiation influence the crystallization of new tyramine polymorphs and their cocrystallization with barbital. The findings provide insights into polymorph stability and offer potential applications in molecular encapsulation and optical materials.</div></div><div><div>Polymorphism – the ability of a compound to exist in multiple crystalline forms – needs to be carefully considered in the design of functional materials, particularly in the context of cocrystallization. Tyramine, a biogenic amine, is a promising candidate for polymorph exploration due to its conformational flexibility and ability to form salts. In this study, we investigate the crystallization of tyramine polymorphs using additives and microwave-assisted techniques. Our findings reveal the formation of a new tyramine polymorph and two distinct salts, highlighting the impact of microwave radiation and additive-driven crystallization on polymorph stability and molecular encapsulation. The study demonstrates that the triclinic tyramine polymorph (T2) is thermodynamically more stable due to its lower electronic energy, whereas the monoclinic form (T1) features slightly stronger intermolecular interactions. Over time, in solution, crystals of barbital–tyramine salts (C1 and C2) begin to form, providing an opportunity to assess structural evolution. Optical properties calculations show significant maximum linear birefringence values (0.164 and 0.255) for two polymorphs of tyramine, whereas for C1, this value decreases to 0.095.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 3","pages":"Pages 403-416"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1107/S205225252500288X
John A. Indergaard , Kashfia Mahmood , Leo Gabriel , Gary Zhong , Adam Lastovka , Matthew J. McLeod , Robert E. Thorne
Methods and instrumentation for reaction initiation via mixing followed by rapid cooling allow sample-efficient time-resolved crystallographic studies with sub-10 ms time resolution. The instrumentation is robust, amenable to diverse samples, cost-effective and enables the remote collection of time-resolved X-ray data using standard sample supports and high-throughput cryocrystallography beamlines.
Time-resolved X-ray crystallography has great promise to illuminate structure–function relations and key steps of enzymatic reactions with atomic resolution. The dominant methods for chemically-initiated reactions require complex instrumentation at the X-ray beamline, significant effort to operate and maintain this instrumentation, and enormous numbers (∼105–109) of crystals per time point. We describe instrumentation and methods that enable high-throughput time-resolved study of biomolecular systems using standard crystallography sample supports and mail-in X-ray data collection at standard high-throughput cryocrystallography synchrotron beamlines. The instrumentation allows rapid reaction initiation by mixing of crystals and substrate/ligand solution, rapid capture of structural states via thermal quenching with no pre-cooling perturbations, and yields time resolutions in the single-millisecond range, comparable to the best achieved by any non-photo-initiated method in both crystallography and cryo-electron microscopy. Our approach to reaction initiation has the advantages of simplicity, robustness, low cost, adaptability to diverse ligand solutions and small minimum volume requirements, making it well suited to routine laboratory use and to high-throughput screening. We report the detailed characterization of instrument performance, present structures of binding of N-acetylglucosamine to lysozyme at time points from 8 ms to 2 s determined using only one crystal per time point, and discuss additional improvements that will push time resolution toward 1 ms.
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Pub Date : 2025-05-01DOI: 10.1107/S2052252525003604
Ashwin Chari
Recent advances in protein design and protein structure prediction have questioned whether experimental structural biology still has a role to play in research today. The article by Panjikar and Weiss [(2025). IUCrJ, 12, 307–321] partially answers this question and alludes to a role still to be played by structural biology. Several properties of peptide bonds, likely important for function, are described that are absent in protein design and predicted protein structures, and that have largely been overlooked by the structural biology community.
{"title":"Peptide bonds strike back","authors":"Ashwin Chari","doi":"10.1107/S2052252525003604","DOIUrl":"10.1107/S2052252525003604","url":null,"abstract":"<div><div>Recent advances in protein design and protein structure prediction have questioned whether experimental structural biology still has a role to play in research today. The article by Panjikar and Weiss [(2025). <em>IUCrJ</em>, <strong>12</strong>, 307–321] partially answers this question and alludes to a role still to be played by structural biology. Several properties of peptide bonds, likely important for function, are described that are absent in protein design and predicted protein structures, and that have largely been overlooked by the structural biology community.</div></div>","PeriodicalId":14775,"journal":{"name":"IUCrJ","volume":"12 3","pages":"Pages 257-258"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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