Polymorphism and Migratory Chiral Resolution of the Free Base of Venlafaxine. A Remarkable Topotactical Solid State Transition from a Racemate to a Racemic Conglomerate

Eupen, J.T.H. van; Elffrink, W. W. J.; Keltjens, Rolf; Bennema, P.; Gelder, René de; Smits, J.M.; Eck, Ernst R. H. van; Kentgens, A.P.M.; Deij, M.A.; Meekes, Hugo; Vlieg, E.

doi:10.1021/cg700831z

Cited by 30 publications

(42 citation statements)

References 24 publications

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“…Restructuring will occur once the product has formed, where the excess energy can be applied in accommodating the local environment for the newly-formed molecule. These restructuring processes are central to many fields and environments, e.g., ice layers on dust particles in the atmosphere and enantiomer separation 2 . In all cases, understanding the restructuring mechanism will shed light on the nature of the entire system 3 .…”

Section: Molecular Solidsmentioning

confidence: 99%

“…In the present paper, we focus specifically on the formation and evolution of interstellar ices, which is important for questions dealing with star and planet formation and ultimately with the origin of life, specifically concerning the delivery of molecules -like H 2 O, CO 2 and organic molecules -to habitable planets. Molecules that are present in ices on dust particles can become trapped during accretion from dust to planet, or may be transported by comets to existing planets.…”

Section: Molecular Solidsmentioning

confidence: 99%

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Long-timescale simulations of diffusion in molecular solids

Karssemeijer

Pedersen

Jónsson

et al. 2012

Phys. Chem. Chem. Phys.

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Kinetic processes play a crucial role in the formation and evolution of molecular layers. In this perspective we argue that adaptive kinetic Monte Carlo is a powerful simulation technique for determining key kinetic processes in molecular solids. The applicability of the method is demonstrated by simulating the diffusion of a CO admolecule on a water ice surface, which is an important process for the formation of organic compounds on interstellar dust grains. CO diffusion is found to follow Arrhenius behavior and the corresponding effective activation energy for diffusion is determined to be 50 ± 1 meV. A coarse graining algorithm is applied which greatly enhances the efficiency of the simulations at low temperatures, down to 10 K, without altering the underlying physical processes. Eventually, we argue that a combination of both on-and off-lattice kinetic Monte Carlo techniques is a good way for simulating large-scale processes in molecular solids over long time spans.

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Section: Molecular Solidsmentioning

confidence: 99%

Section: Molecular Solidsmentioning

confidence: 99%

Long-timescale simulations of diffusion in molecular solids

Karssemeijer

Pedersen

Jónsson

et al. 2012

Phys. Chem. Chem. Phys.

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“…[23][24][25][26] These multi-epitaxies between enantiomers create bi-dimensional racemic compounds which, for reasons not yet understood, do not expand in the third dimension. Actually there is no conceptual limit between these repetitive epitaxies and the corresponding racemic co-crystal (Figure 13.10).…”

Section: Example 3: a Hybrid Salt-co-crystalmentioning

confidence: 99%

Limits of the Co-crystal Concept and Beyond

Coquerel

2011

Pharmaceutical Salts and Co-Crystals

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In this chapter, views of co-crystals are broadened. Indeed, any classification has its limits and, clearly, the thermodynamics of heterogeneous equilibria can help to replace the concept of the co-crystal in a more general perspective. Co-crystals are nothing other than intermediate compounds. Nevertheless, the concept suffers from intrinsic uncertainties due to the numerous situations in which they can occur such as the continuum between solvate and co-crystals, hybrid salt-co-crystals, multi-epitaxy and so on. It is even possible to find the same partners with simultaneously salt-like and co-crystal-like relationships in a given crystal structure. Therefore, rather than creating questionable terms and maintaining endless semantic debates with poor added value, the scientific community should concentrate more on the three long lasting problems related to intermediate compounds listed below: 1. Prediction of intermediate compounds: indeed, apart from statistical trends (e.g. racemic compounds as detailed in this chapter), there is no way to predict the existence of an intermediate compound with acceptable reliability. 2. Prediction of the attributes of these intermediate compounds: to date the connection between structures and properties is very weak despite the evident interest. 3. How to design a process to obtain those intermediate phases with a good yield and minimum side products? Moreover these processes should fulfil the specifications for the final products such as crystallinity, crystal size distribution, morphology, and so on. These questions are really meaningful from an industrial perspective and for advancing knowledge in the organic solid state.

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“…Statistical analyses demonstrated only about 5 to 10% of the racemates form conglomerates, and aspartic acid falls into the remaining 90% category of a racemic forming system as evidenced by (i) the seeding experiment, and (ii) the solubility test . Several interesting cases such as ( R , S )‐2‐chloromandelic acid, free base of venlafaxine, and disulfide‐based iodoplumbate, whose solid state transition depending on the crystallization conditions can take place either from a racemic compound to a racemic conglomerate or vice versa …”

Section: Introductionmentioning

confidence: 99%

“…2 Several interesting cases such as (R,S)-2-chloromandelic acid, free base of venlafaxine, and disulfide-based iodoplumbate, whose solid state transition depending on the crystallization conditions can take place either from a racemic compound to a racemic conglomerate or vice versa. [3][4][5] Intriguingly, when aspartic acid was crystallized from solutions inside porous media, racemic conglomerate crystals of d-and l-aspartic acid were always produced. 6 Recently, we have also discovered the unusual molecular association of aspartic acid enantiomers in water forming a "racemic conglomerate solution" (CS).…”

Section: Introductionmentioning

confidence: 99%

Propagation of Biochirality: Crossovers and Nonclassical Crystallization Kinetics of Aspartic Acid in Water

et al. 2013

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All experimental procedures discussed could be treated as a screening tool for probing the existence of molecular association among the chiral molecules and the solvent system. The molecular association phases of a racemic conglomerate solution (CS) and a racemic compound solution (RCS), and the templating effect of aspartic acid solid surface were observed to minimize the chance of redissolving racemic conglomerate and racemic compound aspartic acid in water and reforming an RCS in crossovers experiments. Only 1 %wt% of l-aspartic acid was adequate enough to induce a transformation from a racemic compound aspartic acid to a racemic conglomerate aspartic acid. This would make the propagation of biochirality more feasible and sound. However, tetrapeptide, (l-aspartic acid)4 , failed to induce enantioseparation as templates purely by crystallization. Nonclassical crystallization theory was needed to take into account the existence of a CS. Fundamental parameters of the crystallization kinetics such as the induction time, interfacial energy, Gibbs energetic barrier, nucleation rate, and critical size of stable nuclei of: (i) racemic compound aspartic acid, (ii) racemic compound aspartic acid seeded with 1 %wt% l-aspartic acid, (iii) racemic conglomerate aspartic acid, and (iv) l-aspartic acid were evaluated and compared with different initial supersaturation ratios. Morphological studies of crystals grown from the crystallization kinetics were also carried out.

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Polymorphism and Migratory Chiral Resolution of the Free Base of Venlafaxine. A Remarkable Topotactical Solid State Transition from a Racemate to a Racemic Conglomerate

Cited by 30 publications

References 24 publications

Long-timescale simulations of diffusion in molecular solids

Long-timescale simulations of diffusion in molecular solids

Limits of the Co-crystal Concept and Beyond

Propagation of Biochirality: Crossovers and Nonclassical Crystallization Kinetics of Aspartic Acid in Water

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