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文献报告
秦亚楠
20121125
参考文献
Influence of Ultrasound on the Nucleation of Polymorphs of
p-Aminobenzoic Acid
Sandra Gracin, Marketta Uusi-Penttila, and Åke C. Rasmuson*
Department of Chemical Engineering and Technology,
Royal Institute of Technology, S-10044 Stockholm, Sweden
Received February 12, 2005; Revised Manuscript Received May 24, 2005
背景及主要研究内容
针状
<25⁰C
棱柱状
α-form
二聚体
β-form
低S，水，
乙酸乙酯
易于
成核
四元环
>25⁰C
研究不同超声方案对其成核的影响
背景及主要研究内容
P = ({dT}/{dt})mcp
the duration of
each pulse,
Δtson
I = P/A
overall sonication
exposure (OSE),
the pulse
repetition period,
PRP
the percentage of
Maximum intensity
（% MI）
超声
实验部分
实验部分
MSZW
induction
time
Teq= 40, 38, 36,32, 30, and 20 °C
constant cooling rate of 1 °C/min,
one without sonication and the other applying sonication
sonication scheme (1/9-80)
started as the cooling began and was
stopped after nucleation had occurred
Eight series of induction time experiments were performed
to examine how the intensity of sonication, the temperature,
and the supersaturation level influence induction time and the
polymorphic form that crystallizes
实验部分
PRP
%MI
the temperature Tson , chosen with respect to the desired supersaturation
and always at least a few degrees above the expected metastable zone limit
实验部分
Results
Nucleation Temperature
（1）超声存在，出晶温度
增大，即介稳区变窄
（2）超声存在，结果更具
重复性
（3）超声存在，平衡温度
20⁰C，α + β ；其余
均是α
α+β
Results
Induction Time
 only the β –form appears
 The shortest induction time was
6 minutes，corresponding to
the highest average ultrasound
Intensity
 the induction time without
ultrasound is 25-360 min for the
α -form and 240-1140 min for the
β -form at the same temperature
and supersaturation
 the induction time quite clearly
decreases with increasing
average sonication intensity
Results
 the supersaturation is higher
than in series 1-3, and the
measured induction times were
much shorter
 crystallized form is always α.
 the β-form is obtained at lower
supersaturation and the α-form
is obtained at higher
supersaturation
 the induction time decreases as
the average intensity increases
Results
• In series 5, the induction time
decreases quite strongly with
increasing average sonication
intensity from 25 to 2.5 min.
• the polymorphic form that
crystallizes shifts from the β-form
at lower intensity to the α-form at
higher intensity
• in series 6 the induction time is
longer and less dependent on the
sonication intensity
• In series 6 the crystallized form is
always β
Results
• In series 7, the induction times are
fairly long but clearly decrease with
increasing average sonication
intensity.
• in series 7, β-form is obtained.
• at moderate supersaturation, the
sonication leads to that the β-form
can be produced even above the
transition temperature
• in series 8, at low intensity, the βform is obtained, and at high
intensity, the α-form is produced
• The threshold supersaturation for
production of the β-form, tends to
decrease with increasing temperature.
Discussion
 Ultrasonic treatment at all levels of intensity of the present work significantly
shortens the induction time for nucleation of both polymorphic forms
 the induction time in general decreases with increasing ultrasound intensity,
that the influence of ultrasound is more pronounced at low supersaturation,
and that the detailed format of the supply of the ultrasonic energy is less
important
 sonication clearly favors the formation of the β-form
 When the supersaturation is close to the threshold, the intensity of the applied
ultrasound may influence the polymorphic form that crystallizes, and in these
cases a lower intensity promotes the appearance of the β-form
Discussion
 Depending on the solvent, it is well-known that carboxylic acids tend to
form centrosymmetric dimers in solution
 We believe that the kinetic preference for formation of the α-polymorph
even below the transition temperature is due to the presence in the solution
of such centrosymmetric dimer precursors
 In dilute benzoic acid solutions, higher pressures and higher temperatures
weaken the hydrogen bonds of the dimers and hence favor the dissociation
of the hydrogen-bonded carboxylic acid dimers
 In addition, there are several studies on the influence of ultrasound on
acetic acid dimerization, where it has been found that the absorbed
ultrasonic energy generates a shift in the dimer-monomer distribution in
favor of the chain complex dimers and free monomers according to the
scheme presented in Figure 8
Discussion
Discussion
 We assume that the same may apply to PABA. Hence, an interesting
possible explanation to that fact that sonication preferentially promotes
the crystallization of the β-form is that sonication reduces the
centrosymmetric carboxylic acid dimerization in solution, possibly as a
result of the high pressure and temperatures at the collapse of the
cavities in accordance with the hot spot theory.
 Another interesting aspect is the report that polarized laser light
promotes the crystallization of the thermodynamically more stable but
kinetically less favorable γ-polymorph of glycine.
 The γ -polymorph structure consists of helical chains of roughly parallel
head-to-tail glycine molecules. Without polarized laser light the γ polymorph of glycine whose structure consists of hydrogen-bonded
double layers, whose basic unit is a hydrogen-bonded dimer (two
antiparallel glycine molecules) will nucleate
Discussion
 It is suggested that the influence of the polarized laser light is due to
partial alignment of solute molecules because of an interaction
between the solute molecules and the laser-induced electric field.
 In addition, it has been found that gas-phase samples of PABA that are
subjected to laser radiation show the disruption of centrosymmetric
hydrogen-bonded Dimers
 On the other hand, there are significant electrical field gradients during
the collapse of a bubble, and these are strong enough to cause bond
breakage and chemical activity.
 Hence, the preferential crystallization of the β-polymorph of PABA can
perhaps also be explained as being the result of the disruption of PABA
dimers by the ultrasound-induced electric field.
Conclusions
 In the present study, it is shown that sonication significantly reduces the
induction time for nucleation of PABA crystallized in aqueous solutions.
 In addition, it is shown that sonication changes the relationship between the
nucleation kinetics of the α-form and the β-form in favor of the latter.
 Below the transition temperature at 25 °C, the crystallization of the β polymorph becomes faster and more reproducible when ultrasound is
applied.
 The induction time decreases with increasing sonication intensity
 By application of ultrasound, the β –polymorph can also be crystallized
above the transition temperature, as long as the supersaturation is not too
high.
 Close to the critical supersaturation threshold, there is a threshold in
sonication intensity, above which pure β -form is not obtained.
 Overall there is an influence of the sonication average intensity, but there is
no evidence that the more detailed format by which the ultrasound energy is
supplied has an influence.
Conclusions
 There are several reports in the literature showing that sonication may
reduce the induction time for nucleation. However, to our knowledge this
is the first time in solution crystallization that it has been shown that
ultrasound may have an influence such that one polymorph in particular
is promoted.
 Our hypothesis is that this effect is due to an influence on the solute
structuring in the solutions the clustering that precedes the nucleation of
the two polymorphs. The α-form structure is based on centrosymmetric
carboxylic acid dimers. It is believed that the tendency to form dimers in
the solution explains why there is a strong preference for the formation
of the α-polymorph in an ordinary crystallization.
 When ultrasound is applied, it is known from the literature that this
dimerization tends to decrease, and it is our hypothesis that this is the
explanation for the increased opportunity for the β-form to appear when
the crystallizing solution is exposed to ultrasound.
Thank You!