Strong H-bonds Research Articles

Synthesis, crystal structure, Hirshfeld surface analysis and bioactivity of the Cu mixed-ligand complex with 4-hydroxybenzoic acid and monoehtanolamine

The new coordination compound [Cu(PHBA) 2 (MEA) 2 ] (MC) (PHBA = p-hydroxybenzoic acid, MEA=monoethanolamine) has been obtained at 28 °C by the reaction in ethanol solution of PHBA, MEA and freshly prepared copper hydroxide. The structure of MC was determined by the single crystal X-ray diffraction. The complex molecules are located on inversion centers. Two PHBA and two MEA molecules are coordinated by metal ions in mono- and bidentate fashions leading to formation of polyhedrons in the form of distorted octahedrons. Molecular conformation is stabilized by strong intramolecular H-bonds between hydroxyl group of MEA and oxygen atom of PHBA. Complex molecules are packed into 2-D supramolecular substructure by intermolecular H-bonds which are further associated into 3-D network through π⋯π interactions. The Hirschfeld surface analysis indicates that the most important contributions to the crystal structure are from H⋯H (about 54%), H⋯O/O⋯H (around 26%) and C⋯H/H⋯C (11.8%) interactions. Tests of a MC impact on the development of plants in example of cotton attested that prepared compound distinctly accelerates growth in all phases of the plant development and increases productivity up to 35%.

Morphology and Intramolecular Interactions in P(VDF-TrFE) Electrospun Nanofibers Doped with Disperse Orange 3 Dye: A Joint Infrared Spectroscopy and Electron Microscopy Study.

In this study, we describe a host–guest system consisting of a push–pull dye, the 4-amino-4′-nitroazobenzene (Disperse Orange 3, DO3), mixed with the copolymer poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] as a potential candidate for nonlinear optics (NLO) applications. We developed electrospun nanofibers of the polymer/dye blend, showing a highly anisotropic molecular structure, where DO3 molecules are mostly oriented parallel to the polymer chain, running in the fiber axis direction. The technique opens a way for obtaining non-centrosymmetric ordering of the NLO chromophore without requiring further poling. The supramolecular architecture is deeply investigated through infrared vibrational spectroscopy, which allows detecting a new phase involving DO3 molecules linked together by strong directional H-bonds. Electron microscopies highlight peculiar nanofiber morphologies with a preferred localization of DO3 at the surface layers.

Photo-curing preparation of biobased underwater adhesives with hydrophobic chain-ring interlace structure for protecting adhesion

Adhesives with long-lasting and reversible adhesion to various underwater surfaces have a wide range of potential applications. However, the development of adhesives for underwater applications is challenging because the surface hydration layer weakens the intermolecular interactions such as hydrogen bonds (H-bonds). Herein, a simple and effective UV-curing strategy was proposed for the preparation of a strong, reusable, and durable biobased underwater adhesive with the combination of fatty acid chains and isobornyl rings as hydrophobic protection for H-bonds interactions. Specifically, a palm oil (PO)-derived monomer, PO fatty acid-ethyl acrylamide (POFA-EA), was chosen owing to its unique amphipathic structure, wherein the amide groups formed strong H-bonds with substrates and the long fatty acid chains served as hydrophobic protection layers. The ring structure of isobornyl acrylate (IBOA) which was used as a comonomer further enhanced the hydrophobic protection. The hydrophobic protection mechanism was confirmed by molecular dynamic simulation combined with experimental verification. The prepared poly(POFA-EA–IBOA) underwater adhesives exhibited a good energy dissipation efficiency (66.4%), and thus, it could reduce the damage caused by adhesive deformation. The adhesives can adhere to a metal surface underwater for up to 15 days and be reused for more than 50 times. This study provides a new hydrophobic protection strategy for the preparation of inexpensive, tough, reusable, and long-lasting underwater adhesives from renewable feedstocks.

Water Dynamics and Structure of Highly Concentrated LiCl Solutions Investigated Using Ultrafast Infrared Spectroscopy.

In highly concentrated salt solutions, the water hydrogen bond (H-bond) network is completely disrupted by the presence of ions. Water is forced to restructure as dictated by the water-ion and ion-ion interactions. Using ultrafast polarization-selective pump-probe (PSPP) spectroscopy measurements of the OD stretch of dilute HOD, we demonstrate that the limited water-water H-bonding present in concentrated lithium chloride solutions (up to four waters per ion pair) is, on average, stronger than that occurring in bulk water. Furthermore, information on the orientational dynamics and the angular restriction of water H-bonded to both water oxygens and chloride anions was obtained through analysis of the frequency-dependent anisotropy decays. It was found that, when the salt concentration increased, the water showed increasing restriction and slowing at frequencies correlated with strong H-bonding. The angular restriction of the water molecules and strengthening of water-water H-bonds are due to the formation of a water-ion network not present in bulk water and dilute salt solutions. The structural evolution of the ionic medium was also observed through spectral diffusion of the OD stretch using 2D IR spectroscopy. Compared to bulk water, there is significant slowing of the biexponential spectral diffusion dynamics. The slowest component of the spectral diffusion (13 ps) is virtually identical to the time for complete reorientation of HOD measured with the PSPP experiments. This result suggests that the slowest component of the spectral diffusion reflects rearrangement of water molecules in the water-ion network.

Molecular dynamics investigation of non-ionic deep eutectic solvents

All-atom molecular dynamics simulations have been employed to study deep eutectic solvents (DESs) consisting of thymol or naphthol as hydrogen bond donor (HBD) and menthol as hydrogen bond acceptor (HBA). Radial and spatial distribution functions demonstrate the presence of specific interactions between the components in both systems. The highest percentage of strong H-bond was found in the pair having the phenolic systems as HBD and menthol as HBA. The number of hydrogen bonds formed between various components decreases with an increase in temperature. Self diffusivity of the non-ionic DESs is higher than that of ionic DESs. Liquid – vapor interfaces of all the systems are enriched with HBAs.

Hydrogen Bond-Enhanced Nanoaggregation and Antisolvatochromic Fluorescence for Protein-Recognition by Si-Coumarins.

Silicon-substituted coumarin (SiC) was established as a substantial family of both intramolecular and intermolecular hydrogen bond (H-bond) enhanced fluorescent probes for sensitively tracking proteins in vivo through the assemble and disassemble of its nanoaggregates. The intramolecular H-bond in SiC has led to significant aggregation, antisolvatochromism, and strong fluorescence with bathochromically shifted spectra into far-red or near-infrared (NIR) regions in polar, protic environments. Without further furnishing with organic linkers, the compact skeleton of SiC bearing H-bond has ensured sensitively and selectively sensing the targeting proteins with the protic reaction pockets through efficient disassemble of the aggregates. In the existence of strong intermolecular H-bonds with the target protein pocket, SiC resolved as high as >250-fold fluorescence enhancement. Selectively tracking proteins, including human serum albumin, human carbonic anhydrase (hCAII), avidin, SNAP-tag protein, and translocator protein, has confirmed SiC a versatile skeleton for sensitively monitoring proteins in complicated biological systems.

Excitation of rhodamine 800 in aqueous media: a theoretical investigation.

The main goal of this work was to obtain a calculated absorption spectrum of rhodamine 800 in an aqueous solution, which most accurately reproduces the experimental one. To achieve this result, I used the hybrid functionals supported by Gaussian 16 software package. In this case, the basis set (6-31++G(d,p)) and the solvent model (IEFPCM) were not varied. The B3PW91 functional gave the best agreement with the experimental absorption spectrum of the dye in an aqueous medium. B3P86, B971, B972, B98, X3LYP, APF, HSE06, and N12SX functionals also give good absorption energy coincidence. The B3PW91/6-31++G(d,p)/IEFPCM theory level chosen in this way made it possible to calculate the various characteristics of rhodamine 800 in the ground and excited states. An important result of this work was the establishment of the vibronic nature of the short-wavelength smaller maximum of the absorption spectrum. The influence of the strong H-bond of the exocyclic nitrogen atom with the water molecule on the dye excitation was analyzed.

Synthesis and bader analyzed cobalt-phthalocyanine modified solar UV-blind β-Ga2O3 quadrilateral nanorods photocatalysts for wide-visible-light driven H2 evolution

In this work, an efficient wide solar light-driven photocatalyst based on solar UV-blind β-Ga2O3 quadrilateral nanorods (β-GOR) has been modified with cobalt phthalocyanine (CoPc). Guided by density functional theory (DFT) calculations and experimental results, H-bond strengthened interfacial connection was established to purchase wide range of solar radiations and applied as an efficient photocatalysts for H2 evolution from water. The optimized 3CoPc/β-GOR nanocomposite unveiled an unprecedented in the quantum efficiency (0.38%) at 660 nm excitation wavelength with outstanding structural stability compare to the pristine solar UV-blind β-GOR (0%). The much extended photoactivities are accredited to the formation of strong H-bond between CoPc and β-GOR, that accelerated charge transformation as confirmed from Bader charge/work function analysis, activation of O2, wide visible-light absorption, as well as joint DFT and experimental results. We believe that this system will also work for other metal phthalocyanines such as ZnPc, NiPc and HPc together with β-GOR towards next-generation efficient photocatalysts with wide-visible light response.

Structural investigation and Hirshfeld surface analysis of two polymorphs of 2-(4-Methylbenzamido)-5-(4-fluoro-3-phenoxyphenyl)-1,3,4-thiadiazoles

In this report, the crystal structure of a new polymorphic form of 2-(4-Methylbenzamido)-5-(4-fluoro-3-phenoxyphenyl)-1,3,4-thiadiazole have been investigated and compared with the previously reported form. Crystallization experiments from a non-polar solvent resulted in the formation of a newly obtained polymorph of this substituted 1,3,4 thiadiazole compound. Structural differences and similarities in both the polymorphic forms were explored in terms of supramolecular building blocks present in the crystal packing and their influences on the supramolecular construct are investigated in terms of the nature and energetics of the associated interactions. In addition, Hirshfeld surface analysis and calculations on the enrichment ratio were carried out for both the forms to isolate the various types of interatomic contacts and differentiate their contribution towards the molecular assembly, as obtained from 2D fingerprint plots. Also, the interaction energies were computed for the new polymorph and compared with the reported form. The studies render quantitative insights into the role of strong H-bonds and weak intermolecular interactions acting cooperatively in the crystal. In addition, the role of both electrostatic and dispersion energies contributes to the overall stability in the crystal packing.

Comparison of Proton Acceptor and Proton Donor Properties of H2O and H2O2 in Organic Crystals of Drug-like Compounds: Peroxosolvates vs. Crystallohydrates.

Two new peroxosolvates of drug-like compounds were synthesized and studied by a combination of X-ray crystallographic, Raman spectroscopic methods, and periodic DFT computations. The enthalpies of H-bonds formed by hydrogen peroxide (H2O2) as a donor and an acceptor of protons were compared with the enthalpies of analogous H-bonds formed by water (H2O) in isomorphic (isostructural) hydrates. The enthalpies of H-bonds formed by H2O2 as a proton donor turned out to be higher than the values of the corresponding H-bonds formed by H2O. In the case of H2O2 as a proton acceptor in H-bonds, the ratio appeared reversed. The neutral O∙∙∙H-O/O∙∙∙H-N bonds formed by the lone electron pair of the oxygen atom of water were the strongest H-bonds in the considered crystals. In the paper, it was found out that the low-frequency Raman spectra of isomorphous crystalline hydrate and peroxosolvate of N-(5-Nitro-2-furfurylidene)-1-aminohydantoin are similar. As for the isostructural hydrate and peroxosolvate of the salt of protonated 2-amino-nicotinic acid and maleic acid monoanion, the Raman spectra are different.

Elucidating the theoretical evolution of the IR spectral density and the potential energy surfaces of hydrogen bonded complexes: A quantum Dynamical study

Concerted potentials are proposed herein for the description of vibrational modes in hydrogen bonded systems to consistently determine the evolution of the infrared absorption spectrum from weak to strong hydrogen bonds. A double well potential constructed using two crossed Morse curves is particularly employed to describe the high stretching mode whereas the H-bond Bridge is designated using harmonic potential. Within the circumstances of the strong anharmonic coupling theory, a strenuous coupling between the high frequency (ω∘) and the H-bond Bridge (ω∘∘) modes is introduced. We consider in this work theoretical IR spectral density of the high frequency stretching mode of hydrogen bonds of the type X-H…Y within the frame of the linear response theory. For this purpose, several experimental correlations are introduced, namely the two angular frequencies ω∘(R) and ω∘∘(R), the barrier height V∘(R), the distance D(R) between the minima and the distance X-H, re (R), which are correlated to the R = RX−Y distance between the two bulks X and Y. The relaxation of the fast mode is incorporated using the theory rationalized by Rosh and Ratner. Fourier transform of the autocorrelation function of the dipole moment operator of the fast mode is employed to determine the IR spectral density. The evolution of the infrared absorption spectrum as well as the evolution of the energy surface potential from weak to strong H-bonds are demonstrated. Realistic evolution of the spectral density is found when weak anharmonic coupling parameters between the fast and slow modes are used. Altogether, our findings highlight the importance of the usage of crossed Morse potentials sampling in the quantum dynamics simulations of the IR spectral density of hydrogen bonded systems with different strengths.

Computational insight into networking H-bonds in open and cyclic forms of galactose

In this work, the intramolecular H-bonds in galactose were studied using DFT at the B3LYP/6–311++G (d,p) levels of theory, atoms in molecules (AIM), and natural bond orbital (NBO). AIM and NBO analysis revealed a cooperative network of trifurcated, bifurcated, and normal H-bonds for the conjugate bases of open galactse (O-Gal). While for the conjugate base of the cyclic form of galactose, we identified bifurcated and normal H-bonds, which may highlight a crucial feature of the biological activity of a whole class of natural sugars. The O-H…O bonds are categorized as mostly electrostatic, strong H-bonds and more favorable, whereas for multiple interactions involving C=O...H, C-H…O and C-H…H-C (dihydrogen bonding) interactions are categorized as weak H-bonds bonds in the conjugate base of considered sugar. The theoretical results indicated that based on acidity values (ΔHacid), galactose in open form (O-Gal) is more acidic than cyclic form (Gal).The acidity value for galactose in open and cyclic forms exhibit significantly lower values (i.e., stronger acid) compared to the reported acidity value for α-/ß- anomers of D-glucopyranose and simple alcohols because their conjugate bases are more stabilized through intramolecular H-bonds like trifurcated and bifurcated, which are studied in details using AIM and NBO analysis.

Quantifying the effects of cooperative hydrogen bonds between vicinal diols on polymer dynamics.

Transient cross-links such as hydrogen bonds (H-bonds) are a central concept for creating polymers with mechanical functionalities, including toughness and self-healing properties. While conventional strong H-bonding groups are based on rigid and planar molecular motifs with multidentate intermolecular interactions, we recently discovered that a structurally simple and flexible vicinal diol (VDO) could serve as a robust yet dynamic cross-link with multiple intermolecular H-bonds between hydroxy groups. In this work, we investigated the effects of cooperativity of H-bonds in VDOs on polymer dynamics. We synthesized model polybutadienes with either VDO or monool (MO) side groups by a radical-mediated thiol-ene click reaction. The oscillatory shear rheology data were analyzed by using the sticky Rouse model. The characteristic time of a single modified segment (δτ0) was significantly longer for the VDO-modified polymers than for the MO-modified polymers, even when they had the same number density of hydroxy groups. The increase in δτ0 with increasing degree of modification was much more drastic for the VDO-modified polymers than for the MO-modified polymers. Moreover, the characteristic time of an unmodified Rouse segment (τ0) was found to increase upon increasing the number of VDOs in the chain, while it was unchanged against the number of MOs. These observations highlight the cooperative effects of placing two hydroxy groups in a close vicinal arrangement. The multiplicity of H-bonds and the structural flexibility of VDOs led to efficient retardation of the chain dynamics.

Cistus incanus’un Bazı Biyoaktif Moleküllerinin SARS CoV-2 ye Karşı Moleküler Doking Analizi

Coronavirus disease affects all the world with the pandemic way that we are still living. The fight against the disease continues with vaccination all over the world. Considering the protection time and the difficulties in attaining the vaccine, in order to be successful in fighting against the disease, we need drugs that enable to kill or hinder replication of the viruses. In drug studies, after analyzing the effect of phytochemicals on the viruses, isolated phytochemical is modified in order to synthesize a more effective molecule. It is not possible to analyze the anti-viral activity of each isolated molecule by in-vitro methods, and in-silico methods can help to overcome this problem. Cistus incanus is a plant whose anti-viral activity has been confirmed by previous trials on many viruses. In this study, the interaction of myricetin 3-O-hexoside, myricitrin, quercitrin and kaempferol 3-O-rutinocide which were detected in the Cistus incanus, were analyzed by molecular docking methods with papain-like protease and main protease crystal. Strong H-bonds were detected between the investigated molecules and papain-like protease and main protease.

The Grotthuss mechanism for bifunctional proton transfer in poly(benzimidazole).

Poly(benzimidazole) (PBI) has received considerable attention as an effective high-temperature polymer electrolyte membrane for fuel cells. In this work, the Grotthuss mechanism for bifunctional proton transfer in PBI membranes was studied using density functional theory and transition state theory. This study focused on the reaction paths and kinetics for bifunctional proton transfer scenarios in neutral ([PBI]2), single (H+[PBI]2) and double-protonated (H2+[PBI]2) dimers. The theoretical results showed that the energy barriers and strength for H-bonds are sensitive to the local dielectric environment. For [PBI]2 with ε = 1, the uphill potential energy curve is attributed to extraordinarily strong ion-pair H-bonds in the transition structure, regarded as a ‘dipolar energy trap’. For ε = 23, the ion-pair charges are partially neutralized, leading to a reduction in the electrostatic attraction in the transition structure. The dipolar energy trap appears to prohibit interconversion between the precursor, transition and proton-transferred structures, which rules out the possibility for [PBI]2 to be involved in the Grotthuss mechanism. For H+[PBI]2 and H2+[PBI]2 with ε = 1, the interconversion involves a low energy barrier, and the increase in the energy barrier for ε = 23 can be attributed to an increase in the strength of the protonated H-bonds in the transition structure: the local dielectric environment enhances the donor–acceptor interaction of the protonated H-bonds. Analysis of the rate constants confirmed that the quantum effect is not negligible for the N–H+ … N H-bond especially at low temperatures. Agreement between the theoretical and experimental data leads to the conclusion that the concerted bifunctional proton transfer in H2+[PBI]2 in a high local dielectric environment is ‘the rate-determining scenario’. Therefore, a low local dielectric environment can be one of the required conditions for effective proton conduction in acid-doped PBI membranes. These theoretical results provide insights into the Grotthuss mechanism, which can be used as guidelines for understanding the fundamentals of proton transfers in other bifunctional H-bond systems.

A 3D supramolecular assembly based on a {AsW12} cluster and in-situ ligand modified metal-organic complexes for photocatalytic properties and electrocatalytic sensing for detection of hydrogen peroxide

A Keggin-type arsenotungstate supramolecular assembly modified with metal-organic complexes, {Zn(dpb)2}2{AsWVI11WV O40}·4H2O (1) (dpb ​= ​2,6-di(2-pyridine)-4,4′-bipyridine), have been synthesized under hydrothermal condition and fully characterized by routine method. In compound 1, each {AsW12O40} cluster is attached to eight Zn(dpb)2 complexes, which are further attracted by four Keggin analogues, forming a tightly packed three-dimensional supramolecular network through strong H-bonds and π-π interactions. It is worth noting that the dpb ligand in the complex {Zn(dpb)2} is produced from the ptz and dpp precursor via under hydrothermal conditions for the first time and its possible assembly path is discussed. The stacking pattern of compound 1 can be simplified to 4,8-connected network with topology {410·610·88}{45·6}2. Compound 1 modified glassy carbon electrode (1-GCE) exhibits significant electrocatalytic reduction activity and outstanding sensing performance for H2O2 with low detection limit (0.43 ​μM) and wide linear range (1.28 μM-2.23 ​mM). Meanwhile, it has high efficiency photocatalytic degradation performance for refractory dyes under ultraviolet irradiation.

Theoretical insights into the gas/heterogeneous phase reactions of hydroxyl radicals with chlorophenols: Mechanism, kinetic and toxicity assessment

Emission of 2-chlorophenols (2-CPs) can cause serious air pollution and health problems. Here, the reaction kinetics and products of key radicals in 2-CPs photo-oxidation are explored in both gaseous and heterogeneous reactions. Quantum chemical calculations show that •OH-addition pathways are more preferable than H-abstraction pathways in gas phase, while that is opposite in heterogeneous phase. At 298 K, the overall rate coefficients of the title reactions in gas and heterogeneous phases are 3.48 × 10−13 and 2.37 × 10−13 cm3 molecule−1 s−1 with half-lives of 55.3 h and 81.2 h, respectively. The strong H-bonds between linear Si3O2(OH)8 and 2-CPs change the energy barriers of initial •OH-addition and H-abstraction reactions, resulting in the competition between heterogeneous reactions and gas phase reactions. The products in heterogeneous reactions are chloroquinone and HONO, which can cause atmospheric acid deposition and eco-toxicity. In gas phase, self-cyclization of alkoxy radical (RO•) leads to formation of •HO2 and highly‑oxygenated molecules, which cause formation of secondary organic aerosol. It is emphasized that oxidation of 2-CPs by •OH leads to formation of more toxic products for aquatic organisms. Therefore, more attention should be focused on the products originated from •OH-initiated reactions of (2-)CPs in gaseous and heterogeneous reactions.

Pharmaceutical organic salt: Disordered crystal structure of levofloxacin with γ-resorcylic acid

This study reports an organic salt prepared from an antibacterial drug, levofloxacin and antioxidant γ-resorcylic acid. A simple preparation method leads to a crystal with disordered structure. The idea is to prepare an organic salt comprising of pharmaceutically acceptable acidic and basic components. The salt is characterised by IR, solid state NMR, and single crystal XRD. Crystal data for C25H26N3O8F: triclinic, space group P-1 (no. 2), a = 7.0037(8) Å, b = 12.764(3) Å, c = 13.909(3) Å, α = 104.821(4)°, β = 92.039(4)°, γ = 95.334(4)°, V = 1194.6(4) Å3, Z = 2, T = 296(2) K, μ(MoKα) = 0.113 mm-1, Dcalc = 1.433 g/cm3, 16879 reflections measured (5.048° ≤ 2Θ ≤ 54.186°), 5139 unique (Rint = 0.0663, Rsigma = 0.0975) which were used in all calculations. The final R1 was 0.1121 (I>2σ(I)) and wR2 was 0.2505 (all data). SC-XRD analysis shows that the crystal packing is stabilized by strong H-bonding of type N-H···O and comparatively weak interactions of type C-H···O, C-H···π and off-set π···π stacking.

Supramolecular polyurea hydrogels with anti-swelling capacity, reversible thermochromic properties, and tunable water content and mechanical performance

Supramolecular polyurea (PU) hydrogels with combined anti-swelling capacity, thermochromic properties, and tunable water content and mechanical performance were obtained by immersing phase separated PU films with hydrophilic soft segments in water till swelling equilibrium. The multiple H-bonds within hard-segment domains are critical to the swelling and mechanical properties, which were rationally designed by using simultaneously two aliphatic diisocyanates with different symmetry and varying molar ratio. Consequently, the hydrogels exhibit a wide range of equilibrium water content (57–80%), elastic modulus (22–476 kPa), breaking strength (33–1720 kPa), and elongation at break (160–1460%). The hydrogels also exhibit fast recovery during cyclic loading-unloading. The incorporation of strong quadruple H-bonds into hard-segment domains endowed the hydrogels with stable anti-swelling capacity. Additionally, the hydrogels changed from transparent to opaque reversibly upon heating and cooling, originating from the phase transition of soft segments. The developed supramolecular PU hydrogels show promising potentials in many fields like smart windows.

Structures of a Phosphoryl Derivative of 4-Allyl-2,4-dihydro-3H-1,2,4-triazole-3-thione: An Illustrative Example of Conformational Polymorphism

Two polymorphic forms of a conformationally flexible molecule, 5-[(Diphenylphosphoryl)methyl]-4-(prop-2-en-1-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione, were obtained by crystallization and characterized by X-ray diffraction analysis and differential scanning calorimetry. The relative stability of polymorphic forms was estimated with DFT calculations of crystal structures and isolated molecules. It turns out, that in the first more dense polymorph with higher cohesion energy and crystal lattice energy, the molecule adopts an energetically unfavorable conformation, and forms dimers with lower H-bond strength, as compared to the second polymorph. On the other hand, in the second polymorph, the molecule adopts almost the lowest-energy conformation and forms infinite chains via strong H-bonds. The first form that seems to be more thermodynamically stable at room temperature transforms into the second form via two endothermic phase transitions; the apparent irreversibility of the transition is due to high energy difference between the molecular conformations in crystals.