别嘌醇随温度变化Temperature Dependent Terahertz Spectroscopy of Allopurinol

Temperature Dependent Terahertz Spectroscopy of AllopurinolQian Song &Pengyu Han &X.-C.Zhang &Cunlin Zhang &Yuejin ZhaoReceived:28December 2008/Accepted:18February 2009/Published online:5March 2009#Springer Science +Business Media,LLC 2009Abstract We report terahertz (THz)characterization of allopurinol over a broad frequency range of 0.2THz to 20THz at different temperatures.The combined use of THz time domain spectroscopy and Fourier transform infrared spectroscopy provides complete coverage of the whole terahertz range.The results show that allopurinol has many prominent absorption signatures within terahertz range,which are determined by the structure and properties of the sample.The absorption spectra from room temperature to below liquid nitrogen temperatures are obtained.The observed blue shifts of the absorption fingerprints at low temperatures are analyzed by Bose-Einstein distribution.Keywords Terahertz spectroscopy .Allopurinol .Fourier transform infrared spectroscopy .Temperature dependent1IntroductionFourier transform infrared spectroscopy (FTIR)has a wide variety of applications in the study of material science.This has been,in part,due to the commercial availability of FTIR instruments with high resolution and signal-to-noise ratios (SNR)[1].FTIR provides specific information about chemical bonding and molecular structures,making it a useful tool for analyzing both organic and inorganic materials [2,3].However,FTIR spectroscopy is most useful in high frequency (mid-infrared),and has low SNR at lower frequencies.The advent of THz time domain spectroscopy (TDS)makes it possible to cover the lower frequency (0.1to 3THz)with very high SNR.In recent years,terahertz spectroscopyJ Infrared Milli Terahz Waves (2009)30:461–467DOI 10.1007/s10762-009-9477-7Q.Song :Y .Zhao (*)Department of Optical Engineering,Beijing Institute of Technology,Beijing,China 100081e-mail:yjzhao@Q.Song :P.Han :X.-C.ZhangCenter for terahertz research,Rensselaer Polytechnic Institute,Troy,NY 12180,USA C.ZhangDepartment of Physics,Capital Normal University,Beijing,China 100037technology has been employed to investigate a variety of materials from solids to gases aided by the improvements in THz emitters and detectors[4–10].Allopurinol is one of the purines that are the building blocks of DNA.Investigation of THz spectra of purines is of fundamental importance in various fields of research,allowing further understanding of the vibrations of DNA and relevant biological reactions and activities in the THz range.In addition,the knowledge of low energy states is crucial for the interpretation of the effect of THz radiation on biological systems.In this paper,we report experimental investigation of allopurinol in the THz range using both FTIR and THz-TDS.Moreover,THz-TDS of allopurinol from room temperature to below liquid nitrogen temperature is performed to have a detailed understanding of its structural properties and collective motions of molecules.2Experimental methodology2.1THz-TDSA typical THz-TDS system was employed to characterize the allopurinol sample.A femtosecond laser with~100fs pulse duration,800mW average power and780nm centre wavelength was employed.THz radiation was generated by part of the laser beam from the surface of an InAs crystal.The detector was a1mm-thick ZnTe crystal.The peak SNR was above1000:1.To eliminate the effect of the water absorption lines in this spectral region,pure nitrogen was used to purge the entire THz path.For the low temperature experiments,a Janis closed cycle refrigerator system(CCR)was used to cool down the sample and control the temperature.The CCR systems provide a convenient means of cooling samples to temperatures below10K,and can be used to perform a wide variety of optical and electrical experiments between~8K and325K(475K optional).CCR systems require no liquid helium or liquid nitrogen as a source of cooling.Instead,a closed loop of helium gas is compressed and expanded,based on the Gifford-McMahon(G-M)thermodynamic cycle.During the expansion phase of each cycle,heat is removed from the cold finger,on which the sample is mounted.A heater and thermometer are installed on the cold finger and are used to precisely control the sample temperature.The temperature was first set to the lowest value,and then raised step by step.The allopurinol under test was commercially available powder,which was mixed with polyethylene with a weight ratio of1:5.To get accurate absorbance,we must make sure that the polyethylene in the sample and the reference has the same weight,so electronic scale with high precision was employed to measure them.The mixture was compressed mechanically(with5 tons pressure)into pellets with a thickness1.5mm.The diameter of the sample is13mm.All samples were measured in transmission mode.THz transmission through a pellet made of only polyethylene was used as reference.We obtained the absorbance of the sample by using Eq.1.ðÞð1ÞA¼Àlog I s=I rIn the equation,I s is the intensity of terahertz radiation that passed through a sample,I r is the intensity of terahertz that has pass through the reference.2.2FTIRA Bruker66V/S FTIR spectrometer was used to study allopurinol in the2-20THz range.FTIR covers different frequency range from the THz-TDS system used in this study and gives complementary information.The FTIR spectrometer employed a Mercury lamp source,a multi-layer mylar beam splitter (T222),and a far-infrared Deuterated triglycine sulfate (DTGS)detector.The spectra were recorded with a resolution of 4cm -1and were averaged 30times.A metal mirror was used as the reference for the reflection measurements.The incident angle was about 6degrees.The aperture was set to 6mm which determine the beam spot size.The diameter of the samples is 19mm,much larger than source beam size to ensure accurate measurement.If the complex refractive index of the sample is N =n +ik ,the amplitude reflectivity r and power reflectivity R are expressed as r ¼ffiffiffiffiffiffiffiffiffiffiffiRe Ài q p ,where θis the phase shift defined in terms of the Fresnel reflection coefficient.ffiffiffiR p and θare correlated according to the Kramers-Kronig (K-K)transform equation.The real part of complex refractive index (N )stands for dispersion,the imaginary part of N stands for absorption.The following equations can be derived:[11]n ¼1ÀR ðÞ.1þR À2ffiffiffiR p cos q ð2Þk ¼2ffiffiffiR p sin q .1þR À2ffiffiffiR p cos qð3ÞTo verify the results obtained from reflection measurement and K-K transform,wemeasured the transmission spectroscopy of the samples as well.For transmission experiment,the 1.5-mm-thick pellet sample was too thick to get a reasonable SNR.The sample powder was dissolved in the acetone first,then the volatile solution was deposited onto a polyethylene film,where a thin alloputinol layer was formed.The thin film sample prepared this way was used for the transmission measurement.3Results and discussionFigure 1shows THz transmission spectra of the allopurinol pellet sample at different temperatures in the 0.2THz -2.4THz frequency range.Two distinct features that are around 0.7THz and 2.2THz can be observed,in agreement with previous measurements.[12]The curves are shifted in amplitude for clarity.At low temperatures,the overall transmission generally increases and thus the broadband background absorption decreases.As temperature is decreased,the reduced homogeneous broadening also results in considerably narrower absorption lines.More interestingly,a blue shift of the absorption peak is observed following the decrease of temperatures.At room temperature,the low frequency resonant peak is about 0.69THz which shifts to 0.705THz at 40K.The relatively high frequency peak at 2.16THz shifts to 2.23THz when the sample is cooled to 40K.Table 1lists the resonance modes of allopurinol at different temperatures.The similarity and consistency in the overall peak shifting indicates that the allopurinol does not undergo a phase transition change upon cooling.One possible explanation about this phenomenon is that when the temperature drops,the crystal cell volume reduces.As a consequence,the decrease of intermolecular separation leads to the increasing of the derivative of potential versus normal coordinate that determines the vibration modes of the crystal.Thus the blue shifts occur.Moreover,if all the contributions to the frequency shift are attributed to phonons,the temperature dependence of the vibrational modes is expected to follow the Bose –Einstein distribution.[13]The frequency shift can be described by [14]v T ðÞ¼v o ÀAT ce T C =T À1ÀÁð4Þ0.30.60.91.21.51.82.10.00.51.01.52.02.53.0 40.3K 82.4K 158.6K 294.8KA b s o r b a n c e (a .u .)Frequency (THz)AllopurinolFig.1THz absorption spectra of allopurinol in the low frequency range.Curves from bottom to top were taken at different temper-atures:294.5K (black curve),158.6K (blue curve),82.4K (green curve),40.3K (red curve).Absorption coefficient spectra are vertically offset for clarity and the lines are guides for the eye.Table 1Temperature dependent frequency modes of allopurinol observed by TDS.Temperature(K)Frequency (THz)Frequency (THz)400.705 2.23820.698 2.2211580.696 2.2022950.692.16501001502002503002.152.162.172.182.192.202.212.222.232.24P h o n o n m o d e s (T H z )Sample temperature (K)Fig.2Temperature dependence of the resonance frequencies near 2.3THz.Solid circles are experimental data,and the red curve is the calculated fit using the empirical expression given in Eq.4.24681012141618200.00.10.20.30.40.5A b s o r b a n c e (a .u .)Frequency (THz)AllopurinolFig.3Absorbance of allopurinol thin film obtained in transmission mode using FTIR.24681012141618200.00.20.40.60.81.01.2 1.01.21.41.61.82.02.2E x t i n c t i o n c o e f f i c i e n t (a .u .)Frequency (THz)kAllopurinolnR e f r a c t i v e i n d e x (a .u .)Fig.4The refractive index (n)and extinction coefficient (k)of allopurinol obtained in reflection mode using FTIR.Table 2Observed THz frequency modes of allopurinol by both TDS and FTIR.Sample TDS (THz)TDS &FTIR FTIR (THz)Allopurinol0.7052.233.095.629.7815.9718.07where n0is the center frequency of the vibration mode at0K and A is a constant.T C is the characteristic temperature related to the energy of the mode.Figure2shows both the experimental and fitted results of the phonon peak centered at2.23THz.The fitting parameters are listed in the inset.Good agreement is observed.Figures3and4show the obtained FTIR spectra in transmission mode and reflection mode respectively.Five more resonant peaks are obtained in the range of3THz~20THz, as can be seen in Table2.The small peak around4THz in the transmission mode figure is regarded as an artifact due to Mie scattering.The peaks below5THz are thought to originate from inter-molecular vibration and the peaks above5THz are attributed to the intra-molecular vibration.In the reflection mode,the refractive index and the extinction coefficients were obtained through K-K transform.THz beam is scattered more strongly by the particles of the samples in transmission,thus the reflection spectrum has an advantage of mitigating Mie scattering which makes signatures less distinct and induces baseline tilt. The resonances obtained from reflection mode match well with those obtained from transmission mode.This confirms the credibility and accuracy of these FTIR measure-ments.Density functional theory(DFT)needs to be applied if the origins of the absorption signatures of allopurinol are to be understood[15].Moreover,the feature at2.2THz is observed from both FTIR and THz measurement that validates the accuracy of both methods.Table2lists the frequencies of all observed vibrational modes of allopurinol from 0.2to20THz.4ConclusionIn summary,we have characterized allopurinol and obtained all resonant absorption signatures in the frequency range of0.2THz to20THz.These absorption resonances are useful for understanding the structures and the vibrational motion of moleculars of allopurinol.Furthermore,we have measured the THz transmission spectra of allopurinol at low temperatures by using THz-TDS from0.2~2.4THz.The observed blue shifts of the peak absorption frequencies at low temperatures are explained by structure-induced lattice potential change.The frequency shift of phonon modes near2.23THz is fitted by Bose–Einstein equation.Acknowledgement We are grateful to the technical support from Dr.Yunqing Chen,Nick Karpowicz, Jingle Liu and Jianxun Liu.References1.A.Salari,and R.E.Young,Application of attenuated total reflectance FTIR spectroscopy to the analysisof mixtures of pharmaceutical polymorphs.Int.J.Pharm.163,157–166(1998).2.P.F.Taday,I.V.Bradley,and D.D.Arnone,Terahertz Pulse Spectroscopy of Biological Materials:L-Glutamic Acid.J.Biol.Phys.29,109–115(2003).3.C.J.Strachan,T.Rades,D.A.Newnham,K.C.Gordon,J.A.Zeitler,M.Pepper,and P.F.Taday,Usingterahertz pulsed spectroscopy to study crystallinity of pharmaceutical materials.Chem.Phys.Lett.390, 20–24(2004).4.R.Huber,A.Brodschelm,F.Tauser,and A.Leitenstorfer,Generation and field-resolved detection offemtosecond electromagnetic pulses tunable up to41THz.Appl.Phys.Lett76,3191(2000).5.Q.Wu,and X.-C.Zhang,7terahertz broadband GaP electro-optic sensor.Appl.Phys.Lett70,1784(1997).6.K.Liu,J.Xu,and X.-C.Zhang,GaSe crystals for broadband terahertz wave detection.Appl.Phys.Lett85,863(2004).7.A.M.Sinyukov,and L.M.Hayden,Generation and detection of terahertz radiation with multilayeredelectro-optic polymer films.Opt.Lett.27,55–57(2002).8.L.M.Hayden et al.,New materials for optical rectification and electrooptic sampling of ultrashort pulsesin the terahertz regime.J.Polym.Sci.:Part B:Polym.Phys41,2492(2003).9.A.M.Sinyukov,and L.M.Hayden,Efficient Electrooptic Polymers for THz Applications.J.Phys.Chem.B108,8515(2004).10.A.M.Sinyukov,M.R.Leahy,and L.M.Hayden,Resonance enhanced THz generation in electro-opticpolymers near the absorption maximum.Appl.Phys.Lett85,5827(2004).11.H.B.Liu and X.-C.Zhang,Terahertz Spectroscopy for Explosive,Pharmaceutical,and BiologicalSensing Applications,Springer;pp251-323.(2007).12.Y.Chen,H.Liu,K.Liu,X.-C.Zhang,THz Spectroscopic Investigation of selected Purines and AminoAcids",IRMMW-THZ200513.L.Vina,S.Logothetidis,and M.Cardona,Temperature dependence of the dielectric function ofgermanium.Phys.Rev.B30,1979(1984).14.Y.C.Shen,P.C.Upadhya,E.H.Linfield,and A.G.Davies,Temperature-dependent low-frequencyvibrational spectra of purine and adenine.Appl.Phys.Lett82,2350(2003).15.D.G.Allis,D.A.Prokhorova,and T.M.Korter,Solid-state modeling of the terahertz spectrum of thehigh explosive HMX.J Phys Chem.A110,1951–1959(2006).。