Polymorphs Of Glycine Research Articles

Insights into the Crystallization and Structural Evolution of Glycine Dihydrate by In Situ Solid‐State NMR Spectroscopy

AbstractIn situ solid‐state NMR spectroscopy is exploited to monitor the structural evolution of a glycine/water glass phase formed on flash cooling an aqueous solution of glycine, with a range of modern solid‐state NMR methods applied to elucidate structural properties of the solid phases present. The glycine/water glass is shown to crystallize into an intermediate phase, which then transforms to the β polymorph of glycine. Our in situ NMR results fully corroborate the identity of the intermediate crystalline phase as glycine dihydrate, which was first proposed only very recently.

Insights into the Crystallization and Structural Evolution of Glycine Dihydrate by In Situ Solid-State NMR Spectroscopy.

In situ solid-state NMR spectroscopy is exploited to monitor the structural evolution of a glycine/water glass phase formed on flash cooling an aqueous solution of glycine, with a range of modern solid-state NMR methods applied to elucidate structural properties of the solid phases present. The glycine/water glass is shown to crystallize into an intermediate phase, which then transforms to the β polymorph of glycine. Our in situ NMR results fully corroborate the identity of the intermediate crystalline phase as glycine dihydrate, which was first proposed only very recently.

Crystallization Behavior of Glycine Molecules with Electrolytic Dissociation on Charged Silica Gel Particles

AbstractThe surface charge of metal oxides in the solution phase may be a driving force for crystallization. Composite particles were prepared using the principle of heterogeneous nucleation on a metal surface with varying charge density. The electrical properties of the silica gel particles in an electrolyte solution were controlled by the pH, and the zero charge point and charge density of the silica gel particles were determined by titration. The morphology of the glycine particles on the silica gel surface depended on the electrical properties of the silica gel particle, resulting in alteration of the glycine polymorph. Powder X‐ray diffraction showed that γ‐glycine was present at low pH, and α‐glycine, at high pH. The polymorphism arose from the abundance ratio of the solute ions and the solution structure.

Does the choice of the crystal structure influence the results of the periodic DFT calculations? A case of glycine alpha polymorph GIPAW NMR parameters computations.

Glycine is a common amino acid with relatively complex chemistry in solid state. Although several polymorphs (α, β, δ, γ, ε) of crystalline glycine are known, for NMR spectroscopy the most important is a polymorph, which is used as a standard for calibration of spectrometer performance and therefore it is intensively studied by both experimental methods and theoretical computation. The great scientific interest in a glycine results in a large number of crystallographic information files (CIFs) deposited in Cambridge Structural Database (CSD). The aim of this study was to evaluate the influence of the chosen crystal structure of α glycine obtained in different crystallographic experimental conditions (temperature, pressure and source of radiation of α glycine) on the results of periodic DFT calculation. For this purpose the total of 136 GIPAW calculations of α glycine NMR parameters were performed, preceded by the four approaches ("SP", "only H", "full", "full+cell") of structure preparation. The analysis of the results of those computations performed on the representative group of 34 structures obtained at various experimental conditions revealed that though the structures were generally characterized by good accuracy (R < 0.05 for most of them) the results of the periodic DFT calculations performed using the unoptimized structures differed significantly. The values of the standard deviations of the studied NMR parameters were in most cases decreasing with the number of optimized parameters. The most accurate results (of the calculations) were in most cases obtained using the structures with solely hydrogen atoms positions optimized. © 2018 Wiley Periodicals, Inc.

Effects of inorganic additives on polymorphs of glycine in microdroplets

Sodium chloride plays an important role in the selectivity of glycine polymorphs and results in an increased nucleation percentage in microdroplets.

Controlling the crystal polymorph by exploiting the time dependence of nucleation rates.

Most substances can crystallise into two or more different crystal lattices called polymorphs. Despite this, there are no systems in which we can quantitatively predict the probability of one competing polymorph forming instead of the other. We address this problem using large scale (hundreds of events) studies of the competing nucleation of the alpha and gamma polymorphs of glycine. In situ Raman spectroscopy is used to identify the polymorph of each crystal. We find that the nucleation kinetics of the two polymorphs is very different. Nucleation of the alpha polymorph starts off slowly but accelerates, while nucleation of the gamma polymorph starts off fast but then slows. We exploit this difference to increase the purity with which we obtain the gamma polymorph by a factor of ten. The statistics of the nucleation of crystals is analogous to that of human mortality, and using a result from medical statistics, we show that conventional nucleation data can say nothing about what, if any, are the correlations between competing nucleation processes. Thus we can show that with data of our form it is impossible to disentangle the competing nucleation processes. We also find that the growth rate and the shape of a crystal depend on it when nucleated. This is new evidence that nucleation and growth are linked.

Computer simulation and experimental self-assembly of irradiated glycine amino acid under magnetic fields: Its possible significance in prebiotic chemistry

Ionizing radiation may have played a relevant role in chemical reactions for prebiotic biomolecule formation on ancient Earth. Environmental conditions such as the presence of water and magnetic fields were possibly relevant in the formation of organic compounds such as amino acids. ATR-FTIR, Raman, EPR and X-ray spectroscopies provide valuable information about molecular organization of different glycine polymorphs under static magnetic fields. γ-glycine polymorph formation increases in irradiated samples interacting with static magnetic fields. The increase in γ-glycine polymorph agrees with the computer simulations. The AM1 semi-empirical simulations show a change in the catalyst behavior and dipole moment values in α and γ-glycine interaction with the static magnetic field. The simulated crystal lattice energy in α-glycine is also affected by the free radicals under the magnetic field, which decreases its stability. Therefore, solid α and γ-glycine containing free radicals under static magnetic fields might have affected the prebiotic scenario on ancient Earth by causing the oligomerization of glycine in prebiotic reactions.

Modeling of glycine solubility in aqueous HCl–MgCl2 system and its application in phase transition of glycine by changing media and supersaturation

The solubility of glycine in HCl and HCl–MgCl2 solutions was measured from 283.15 to 343.15K and found to increase with temperature and increase linearly with the concentration of HCl. The MSE model integrated in the OLI platform was modified by regressing the experimental and literature solubility data through the adjustment of the middle-range interaction parameters. After parameterization, the model can accurately calculate the solubility with the average absolute deviation lower than 3.5% and thus be able to predict supersaturation of glycine. Crystallization of different polymorphs of glycine in water, HCl, NaOH, MgCl2, and HCl–MgCl2 aqueous solutions was performed. The effects of medium, temperature, supersaturation, and time on the crystallization were investigated. It was found that only in the HCl solution the formation of single α-glycine phase was achieved under all the investigated temperature and holding time. α-glycine or its mixture with γ-glycine or C4H18N2O4·HCl was produced in systems other than HCl solution depending on the conditions.

Synthesis and characterization of γ-glycine – a nonlinear optical single crystal for optoelectronic and photonic applications

Abstract A single crystal of gamma-glycine (GG), a polymorph of glycine, was synthesized by crystallization. The single crystal of GG was grown from an aqueous solution. The morphology of GG was studied in order to assess its growth facets. The good quality single crystals were subjected to X-ray diffraction studies to reveal their structure. The FT-IR spectral analysis was carried out to confirm the presence of expected functional groups. The UV-Vis analysis was done for GG single crystals to determine the optical transparency and band gap. Simultaneous TG-DTA analysis was employed to understand the thermal and physicochemical stability of the title compound. The mechanical stability and laser stability of GG single crystal were studied using Vickers microhardness test and laser induced damage threshold on different planes of the crystal to reveal its anisotropic nature. The dielectric measurement was carried out as a function of frequency and the results were discussed. The existence of second harmonic generation (SHG) of the title compound was confirmed by Kurtz-Perry powder technique. The SHG effective nonlinearity and particle size dependence of GG powder sample were compared with a standard reference material: potassium dihydrogen phosphate (KDP).

Supersaturation dependence of glycine polymorphism using laser-induced nucleation, sonocrystallization and nucleation by mechanical shock.

The nucleation of glycine from aqueous supersaturated solution has been studied using non-photochemical laser-induced nucleation (NPLIN), ultrasound (sonocrystallization), and mechanical shock of sample vials. It was found that at higher supersaturation, samples were more susceptible to nucleation and produced more of the γ-glycine polymorph. The results are described in terms of a mechanism common to all three nucleation methods, involving the induction of cavitation events and pressure shockwaves. The switch in preference from α- to γ-glycine was observed to occur over a narrower range of supersaturation values for NPLIN. We attribute this to induction of cavitation events with higher energies, which result in higher localized pressures and supersaturations. Experiments on NPLIN using circularly versus linearly polarized light showed no evidence for binary polarization switching control of glycine polymorphism.

Does the γ Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution

We advance the quantitative study of nucleation by combining the study of hundreds of samples, with statistical tests for reproducibility, and for well-defined nucleation rates. Unlike in most previous work, we find that in the samples that nucleate after the first hour of our experiment the equilibrium glycine polymorph predominates over the alpha form.

Non-Topotactic Phase Transformations in Single Crystals of β-Glycine

The metastable β polymorph of glycine exhibits a single-crystal-to-single-crystal transformation (SCSCT) to either the α or γ phase with retention of the crystal habit of the parent β phase. X-ray diffraction and optical microscopy reveal that of 51 single crystals of the β parent phase, 24 form single domain crystals of α or γ with a single orientation matrix, confirming an SCSCT. The remaining 27 β parent crystals transform to crystals with a few domains of either α and/or γ, each domain arising from a single nucleation event. In three cases the β → α and β → γ transformations occurred within the same glycine single crystal. In all cases, regardless of the number of domains, the transformation occurred with retention of the original habit of the parent phase. Both β → α and β → γ transformations proceed in a non-topotactic manner, as evident from the random orientations of the daughter phases in the crystallographic reference frame of the parent β phase. The transformation rates, as measured by advancem...

Crystal structure prediction from first principles: The crystal structures of glycine

Here we present the results of our unbiased searches of glycine polymorphs obtained using the genetic algorithms search implemented in MGAC, modified genetic algorithm for crystals, coupled with the local optimization and energy evaluation provided by Quantum Espresso. We demonstrate that it is possible to predict the crystal structures of a biomedical molecule using solely first principles calculations. We were able to find all the ambient pressure stable glycine polymorphs, which are found in the same energetic ordering as observed experimentally and the agreement between the experimental and predicted structures is of such accuracy that the two are visually almost indistinguishable.

Attainment of unstable β nucleation of glycine in presence of l-tyrosine and its analytical interpretation—A combined approach

The ability of l-tyrosine molecules to act as a template and to facilitate the nucleation of unstable β polymorph in the solution has been revealed through in-situ nucleation study. This nucleation of β occurs along with the existing α nucleation at the critical concentration of additive in the solution. The presence of l-tyrosine molecules lowers the inherent barrier that exists for β nucleation in the solution. No nucleation of γ was observed over the entire range of concentrations studied. The molecular recognition capability and stereo selective inhibitory action of the added l-tyrosine molecules towards glycine molecule have been successfully revealed in terms of habit modification observed in the nucleated polymorphs. In the case of α polymorph, l-tyrosine induces a change in the morphology along the enantiopolar −b direction while in the case of β polymorph, habit modification from needle to plate like structure is observed. With the increase in time span, solution mediated phase transformation from β to α polymorph has been observed in the solution. Analytically the nucleation parameters of α and β polymorphs were estimated based on Classical Nucleation Theory. Form of crystallization of the nucleated polymorphs of glycine was confirmed by a powder x-ray diffraction analysis.

Optical trapping assembling of clusters and nanoparticles in solution by CW and femtosecond lasers

Laser trapping of molecular systems in solution is classified into three cases: JUST TRAPPING, EXTENDED TRAPPING, and NUCLEATION and GROWTH. The nucleation in amino acid solutions depends on where the 1064-nm CW trapping laser is focused, and crystallization and liquid–liquid phase separation are induced by laser trapping at the solution/air surface and the solution/glass interface, respectively. Laser trapping crystallization is achieved even in unsaturated solution, on which unique controls of crystallization are made possible. Crystal size is arbitrarily controlled by tuning laser power for a plate-like anhydrous crystal of l-phenylalanine. The α- or γ-crystal polymorph of glycine is selectively prepared by changing laser power and polarization. Further efficient trapping of nanoparticles and their following ejection induced by femtosecond laser pulses are introduced as unique trapping phenomena and finally future perspective is presented.

Impact of malonic acid on the segregation of glycine polymorphs – Analytical assisted molecular approach

Proton dissociation assisted negative polarity of malonic acid molecules admist glycine zwitterions leads to orgination of γ nucleation in the solution. Alteration in the nucleation behaviour and segregation of glycine polymorphs in the presence of malonic acid over a wide range of concentrations has been investigated both by experimental and analytical approaches. Complete changeover in the nucleation behaviour from 100% α to 100% γ is observed at the critical concentration of the additive. Shifting in the overall charge environment of the system towards cationic in the presence of malonic acid favours the nucleation of γ through induced charge compensation in the solution. Tuning of merohedral twinning in γ nucleation by the additive concentration has been well revealed in the present work. CNT based analytical approach employed elucidates well the experimental observations through the estimated interfacial energy, volume excess free energy, critical radius, activation energy barrier and nucleation rates of α and γ polymorphs. Structural affirmation of the nucleated polymorphs was carried out by powder x‐ray diffraction.

Nanocrystal formation and polymorphism of glycine

We obtained α-/β-glycine nanocrystals, examined their surface structures and found the solubility ratio of β-form/α-form changes as size decreases.

Change in glycine polymorphs induced by minute-bubble injection during antisolvent crystallisation

In this study, to develop a crystallisation technique that enables the control of polymorphism under constant temperature, we studied the antisolvent crystallisation of glycine using the gas–liquid interfaces around N2 minute-bubbles as new crystallisation fields where nucleation progresses predominantly. At the minute gas–liquid interfaces, local supersaturation increases due to the accumulation of glycine and antisolvent caused by the negative surface potential of the minute-bubbles. Thus, the nucleation rate is faster and the production of metastable/unstable polymorph is accelerated. At a solution temperature of 303K, the saturated glycine solution and methanol as an antisolvent were mixed by the two different addition orders as follows: Gly solution/MeOH system, methanol was added into a saturated glycine solution; MeOH/Gly solution system, a saturated glycine solution was added into methanol. While mixing methanol with the saturated glycine solution, N2 minute-bubbles with an average diameter of 10μm were continuously supplied to the mixed solution using a self-supporting bubble generator and a glycine polymorph was produced. In both systems, the generation rate of supersaturation in the bulk solution (rC/CS) was varied in the range of 1.2–71.3min−1 by controlling the addition rate of methanol or the saturated glycine solution. For comparison, antisolvent crystallisation free of minute-bubbles was performed. Consequently, N2 minute-bubble injection enabled the selective crystallisation of the metastable α-form or unstable β-form at lower rC/CS and decreased the rC/CS necessary for α-form or β-form production by approximately 1/2 during antisolvent crystallisation.

Ultrasound assisted nucleation and growth characteristics of glycine polymorphs – A combined experimental and analytical approach

For the first time, the effect of ultrasound in the diagnostic frequency range of 1–10MHz on the nucleation and growth characteristics of glycine has been explored. The investigation employing the ultrasonic interferometer was carried out at a constant insonation time over a wide range of relative supersaturation from σ=−0.09 to 0.76 in the solution. Ultrasound promotes only α nucleation and completely inhibits both the β and γ nucleation in the system. The propagation of ultrasound assisted mass transport facilitates nucleation even at very low supersaturation levels in the solution. The presence of ultrasound exhibits a profound effect on nucleation and growth characteristics in terms of decrease in induction period, increase in nucleation rate and decrease in crystal size than its absence in the solution. With an increase in the frequency of ultrasound, a further decrease in induction period, increase in nucleation rate and decrease in the size of the crystal is noticed even at the same relative supersaturation levels. The increase in the nucleation rate explains the combined dominating effects of both the ultrasound frequency and the supersaturation in the solution. Analytically, the nucleation parameters of the nucleated polymorph have been deduced at different ultrasonic frequencies based on the classical nucleation theory and correlations with the experimental results have been obtained. Structural affirmation of the nucleated polymorph has been ascertained by powder X-ray diffraction.

Attainment of unstable β nucleation of glycine through novel swift cooling crystallization process

The sudden cooling of mother liquor from high temperature to a temperature below the ambient through the recently introduced swift cooling crystallization process yielded the β nucleation of glycine even in the absence of anti-solvents and additives. Experiments were continued at different supersaturation and stirring levels. The nucleation matrix resulted out of these 135 experiments revealed that, even at lower supersaturation and lower stirring rates, the unstable β nucleation could be achieved. This attained result contrasts the existing reports in which β nucleation is achieved only at higher supersaturation levels. The intermediate supersaturation and stirring levels facilitate both the β and α nucleation through solution mediated phase transformation while the higher supersaturation and stirring levels facilitate only the α nucleation of glycine in the system. The swift cooling method adopted declines the energy barrier that inherently exists for β and enables its nucleation in the system. Analytically the nucleation parameters of β and α polymorphs were estimated based on Classical Nucleation Theory. Form of crystallization of the nucleated polymorphs of glycine was confirmed by powder x-ray diffraction analysis.