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Is Second Harmonic Generation a reliable tool for studying solid-solid phase transition and structural
purity?
S. Clevers, V. Dupray, Florent Simon, G. Coquerel
To cite this version:
S. Clevers, V. Dupray, Florent Simon, G. Coquerel. Is Second Harmonic Generation a reliable tool for studying solid-solid phase transition and structural purity?. XXXVIII èmes JEEP, Mar 2012, Rouen, France. �hal-01942447�
Simon Clevers a , Valérie Dupray a , Florent Simon a and Gérard Coquerel a
a Unité de Croissance Cristalline et de Modélisation Moléculaire, SMS, UPRES EA. 3233, Université de ROUEN, Rue Lucien Tesnière – F-76821 Mont Saint-Aignan Cedex,
[email protected]
Is Second Harmonic Generation a reliable tool for studying solid-solid phase transition and structural purity?
Introduction
Aim of this study : To evaluate the potential of SHG signal measurements to detect the phase transitions by comparison with other usual techniques such as Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction (XRPD). Two samples are studied : a commercial MHBA (normally constituted of the stable form) and a pure metastable product obtained by recrystallization in acetone.
Comparison with Differential Scanning Calorimetry
- In two cases : Average onset fusion peak ≈ 201.7 C
-Recrystallized MHBA DSC scans exhibit a weak exothermic event around 167 C (at 10K/min) attributed to the crystallization of the metastable (Pna2 1 ) form into the stable form (P2 1 /c).
- DSC curves of commercial MHBA exhibit no heat exchange corresponding to a phase transition. In the case of commercial product, this technique can not detect the phase transition.
Exo U p
Commercial MHBA
-0,50 0,00 0,50 1,00 1,50
110 120 130 140 150 160 170 180 190 200 210 220
Relative Heat Flow (mW/g)
Temperature ( C)
1K/min
2K/min
5K/min
10K/min
Comparison with X-Ray Powder Diffraction
Commercial MHBA
- XRPD confirms that :
• the 2 polymorphic forms are present in commercial MHBA.
• the structural impurity highlighted by SHG corresponds to the metastable form.
- Non centrosymmetric peak reference disappears between 142 C and 152 C
16 16,2 16,4 16,6 16,8 17 17,2 17,4 17,6 17,8 18
Relative X-R ay intensity
2θ
172 C
162 C
152 C
142 C
20 C (before Heating) 20 C (After Heating)
Centrosymmetric peaks reference
Non Centrosymmetric peak reference
0 500 1000 1500 2000 2500 3000 3500
20 35 50 65 80 95 110 125 140 155 170 185 200
SHG Intensity (% of KDP SHG Intensity)
Temperature ( C)
Recrystallized MHBA
0 10 20 30 40 50 60
20 35 50 65 80 95 110 125 140 155 170 185 200
SHG Intensity (% of KDP SHG Intensity)
Temperature ( C)
Commercial MHBA
- Exhibits SHG signal
- SHG intensity decreases
progressively with the temperature - 90% of the signal is lost between
100 C and 160 C.
- The SHG signal disappears completely at 170 C. (mean heating rate 2K/min)
- Results similar to the recrystallized product results: Inconsistent with the centrosymmetric space group
assignment.
- The commercial compound exhibits a low SHG signal (55 times less intense than the recrystallized product).
Thermo-SHG
Principle of SHG:
A laser beam is sent on the sample at the fundamental frequency ω
ðIf the sample is non centrosymmetric a SHG signal is detected at twice the fundamental frequency.
ðAccording to the Kurtz and Perry method 1 the signal is compared to a reference signal. In our case, samples were compared to KDP.
Second Harmonic Generation (SHG):
SHG is an optical process which can be used to detect the non-centrosymmetry of crystalline compounds 1,2 (powder form). In order to study phase transitions, a device has been developed to perform SHG measurements versus temperature. The case of 3-hydroxybenzoic acid is considered.
A known irreversible phase transition from the non- centrosymmetric metastable form (SHG Positive) to the centrosymmetric stable form (SHG negative) occurs at circa 160 C 3 .
3-Hydroxybenzoic acid (MHBA) exhibits two polymorphic forms :
O HO
OH
A stable form P2 1 /c (Centrosymmetric space group)
3 6 9 12 15 18 21 24 27 30
Relative X-ray intensity
2θ ( )
SHG negative
3 6 9 12 15 18 21 24 27 30
Relative X-ray intensity
2θ ( )
A metastable form Pna2 1 (Non centrosymmetric space
group)
SHG positive
The SHG device can be used to track this phase transition.
λ, ω
λ/2, 2ω Apparatus :
λ/2 Waveplate
P P
Heating/cooling stage
Spectrometer
Optical fiber probe Nd:Yag
LASER
Sample
Energy adjustment device
computer
ðThe powder sample is placed in an heating/cooling stage (computer controlled).
ðThe SHG signal is measured versus temperature using a spectrometer.
Results:
-SHG allow the monitoring of the polymorphic transition of MHBA from its metastable to its stable form
- SHG can probe the stuctural purity of the sample and track the conversion of a small amount of metastable form.
ð The commercial sample contains a SHG positive compound = small amount of metastable noncentrosymmetric form
SHG and XRPD are complementary techniques
Conclusion
Understanding the possible relationship between the lattice thermal expansion (highlighted by a peak shift in TR-XRPD) and the SHG signal and determine more accurately the temperature of the solid-solid phase transition.
(1) J.P. Dougherty and S.K. Kurtz, J.Appl Crystallogr, vol. 9, no. 2, pp. 145–158, (1976). (2) A. Galland, V.Dupray, B.Berton, S.Morin-Grognet, M.Sanselme, H.Atmani and G.Coquerel, Cryst Growth & Des, vol. 9, no. 6, pp. 2713–2718, (2009).
(3) F. L. Nordström and Å.C. Rasmuson, European J.Pharm Sci, vol. 28, no. 5, pp. 377–384, (2006).
Further Work
-0,50 -0,30 -0,10 0,10 0,30 0,50 0,70
110 120 130 140 150 160 170 180 190 200 210 220
Relative Heat Flow (mW/g)
Temperature ( C)
1K/min
2K/min
5K/min
10K/min
