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Pseudopolymorphism: Concentration dependence

3. Results and discussion

3.2 Pseudopolymorphism: Concentration dependence

In our experiment, it is too difficult to trap the monomer, so liquid-like cluster is the

trapped target which is spontaneous aggregation of L-Phe molecule and D2O solvent due to

concentration fluctuation. Size and amount of liquid-like cluster strongly depends on solution

concentration, and it becomes more with concentration increase. We confirmed that the

spontaneous crystallization at room temperature always provides the monohydrate crystal, 2.2

and 2.7 × 10-2 wt% are unsaturated and supersaturated solution, and the probabilities of

anhydrous and monohydrate crystal formation at room temperature in different concentrations.

After laser irradiation, either supersaturation or saturation even in unsaturation were observed

monohydrate and anhydrous crystal formation in all sample within 30 minutes depending on

the solution concentration, respectively. I summarized all the experiment results in Fig. 3.7. The

Fig. 3.7 Probability of plate-like crystal formation (blue line) and spontaneous crystallization (red line) depending on concentration.

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probabilities of anhydrous and monohydrate crystal formation are calculated by the number of

the crystal form prepared firstly after starting laser irradiation, and the irradiation was often

turned off immediately after the crystal generation. Compared with spontaneous crystallization,

our crystallization time is much shorter. It confirmed that all the crystals were induced by laser,

and they were not spontaneous one even in supersaturation. The probability of anhydrous

crystal formation became clearly high at the low concentration, it indicates anhydrous crystal

formation is dominant in the solution. At high concentration, laser induced spontaneous

crystallization occurred easily in the solution, but anhydrous crystal was still observed at 2.7 ×

10-2 wt%. These results are much different from results in H2O, which indicates the

pseudopolymorphism ware induced in different process again.

Under supersaturation, it shows laser enhanced spontaneous crystallization of

monohydrate crystal always takes place in the solution, but one anhydrous crystal was still

formed in 2.7 ×10-2 wt%. It means some competition may occur between monohydrate and

anhydrous crystal formation, and also illustrates the ability of polymorph controlling and

dehydration induced by laser as described later. As shown in Fig 3.8, initial solution of 2.9 ×

10-2 wt% is full of liquid-like clusters and these liquid-like clusters are efficiently trapped by

laser leads to the aggregate of liquid-like cluster in the focal spot like stage (i). Through the

liquid nucleation, it goes to the stage (ii) where aggregate of liquid-like clusters is transformed

to assembly of liquid-like clusters. In the stage (ii), assembly of liquid-like clusters starts to

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become well-ordered, higher concentration and less solvent molecules. Assembly of liquid-like

clusters which is trapped at focal spot enlarge the trapping potential and enhance trapping force,

and then make high concentration propagating to the outside of focal spot and entering stage (iii). Here, we propose “laser pinning effect.” The alignment of molecules in the focal spot is

reflecting to the polarization of laser, and the effect decrease with the distance from the focal

spot. The alignment pinned by laser in the focal spot is not suitable for monohydrate crystal

formation. As a result, monohydrate crystal always form not at the focal spot, but monohydrate

crystal formation is achieved when molecular alignment become disordered far away from focal

spot. On the other hand, molecules pinned by laser in the focal volume perform the large-linked

molecules or clusters which is the precursor of anhydrous crystal. As local concentration is

Fig. 3.8 Crystallization process of two crystal pseudopolymorphism under different solution concentration.

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increased by laser trapping, the distance between L-Phe molecules becomes closer and the

intermolecular interactions between L-Phe molecules becomes prominent. As a result, L-Phe

molecules themselves directly linked with each other through relatively strong hydrogen bonds,

and it causes local dehydration where strong interaction excluded the solvent, leading to

anhydrous crystal formation. As described in section 2.4, dehydration in H2O is induced by

laser heating which is enough to exceed the transition point 37°C. It is quite different

mechanism between these two, which one is due to temperature elevation and another is

because of intermolecular interaction. In the case of PNIPAM, phase transition is induced when

critical temperature 34°C is achieved. Tsuboi et al. reported laser-induced reversible volume

phase transition of PNIPAM in D2O.59 PNIPAM gel is in a swollen hydrate phase below a

critical temperature, and in a collapsed dehydrate phase above the temperature. Photon pressure

accelerates the dynamic of phase transition, and shift the transition point to lower temperature.

At the focal point, where the photon pressure is exerted, dehydration is promoted, based on

which they suggest that laser-induced shrinkage. This is quite similar with L-Phe, where phase

transition can be regarded as crystal pseudopolymorphism transformation, so we suggest that

laser can exclude the heavy water away from the focal spot, leading to anhydrous crystal

formation. From another viewpoint, this may be another reason that monohydrate crystals were

always generated not at the focal spot.

Under unsaturation (1.7 × 10-2 wt%), there are no L-Phe liquid-like clusters in the initial

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solution, but sometimes L-Phe liquid-like clusters are trapped at the focal spot due to

concentration fluctuation and laser reveals liquid-like clusters where monomer is changed down

the motion at the focal spot and formed local high concentration area (Fig. 3.8, stage (i)).

Through the liquid-nucleation like of supersaturation, assembly of L-Phe liquid-like cluster is

induced by laser and grew up. It is worth to mention that the size and formation rate of assembly

is much smaller and slower than that in supersaturation. It is not large enough to generate

monohydrate crystal at 1.7 × 10-2 wt%, so there is no monohydrate crystal formation as shown

in Fig. 3.8. On the other hand, anhydrous crystal formation still can be triggered by laser

irradiation, where the assembly of large-linked molecules are excluded the heavy water at the

focal spot. We conclude that “laser trapping-induced dehydration”

At the middle concentration, liquid-like clusters are less than supersaturation but higher

than unsaturation in the initial solution, and the expending rate of assembly of liquid-like

clusters are also between 1.7 × 10-2 wt% and 2.9 × 10-2 wt%. Through the same process as

shown in Fig. 3.8, monohydrate and anhydrous crystal are generated in the solution,

respectively. There is sharp decreasing of probability of anhydrous crystal formation in this

concentration range. As we could predict, strong competition between these two crystal

formations should happen in this sharp decreasing area. In the case of polarization dependence,

there is also the biggest difference between three kinds of polarization and the sharp decreasing at the middle concentration. The detail dynamic and mechanism is discussed as follow.

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