Strong piezoelectricity in [H-b-(2-pyridyl)-Ala- OH][BF4] and [H-b-(2-pyridyl)-Ala-OH][ClO4] – new amino acid based hybrid crystals†

New amino acid based [H-b-(2-pyridyl)-Ala-OH][ClO4] and [H-b-(2-pyridyl)-Ala-OH][BF4] crystals were synthesized and their structure and functional piezoelectric properties were investigated in detail. The former crystallizes in the piezoelectric P212121 space group whereas the latter belongs to the polar P1 space group. Piezoelectric force microscopy (PFM) measurements revealed that the piezoelectric coefficient, d15eff, of the [H-b-(2-pyridyl)-Ala-OH][BF4] crystal is more than twice that in the widely used transducer material lithium niobate, LiNbO3. The crystal structures of both [H-b-(2-pyridyl)-Ala-OH] derivatives are characterized by interand intramolecular hydrogen bond networks that are responsible for a high piezoresponse. The existence of intramolecular hydrogen bonding was confirmed by means of IR measurements. The thermogravimetric (TGA) technique was applied to study the thermal behavior of the title crystals. The piezoelectric properties are discussed in the context of the crystallographic structure and the microstructure of these crystals.


Introduction
Crystalline materials without a centre of inversion are known to exhibit piezoelectric properties (except for the 432 space group). Due to the direct piezoelectric effect, these materials, when subjected to mechanical stress, generate an electric charge proportional to that stress and due to the converse piezoelectric effect they generate mechanical stress when an electric field is applied. This property is widely used in many applications including acoustic transducers, piezomotors or sensors and actuators. 1 An important class of piezoelectrics are ferroelectrics, which exhibit piezoelectric constants significantly higher than those found in nature such as minerals or some bio-organic materials (e.g. lamellar-bone, collagen). In this context ferroelectric organic materials are becoming increasingly important because of their potential applications in the areas of microelectronics and micromechanical systems, such as field effect transistors and non-volatile memories. 2,3 Organic compounds are cheaper and their structure can be easily controlled through chemistry as compared to inorganic ferroelectrics/ piezoelectrics. The past decade has experienced significant progress in the search for new organic ferroelectrics useful for microelectronics. 1,4,5 It appears that highly organized molecular dipole assemblies frequently exhibit piezoelectricity due to the presence of polar bonds and natural asymmetry, which is characteristic of many organic biomaterials (proteins, peptides, amino acids and polysaccharides). Furthermore some biomolecules with bias-induced conformational states also possess true ferroelectric properties. 6 One of the most interesting materials for nanoelectronic applications is the alanine derivative, L-phenylalanyl-L-phenylalanine. This material easily self-assembles into tube-like structures. 7 This process that takes place in this dipeptide as well as in L-leucyl-L-leucine, L-leucyl-L-phenylalanine and L-phenylalanyl-Lleucine was studied in detail by  and by Gazit's group. 7,[11][12][13][14] Later on, Kholkin et al. 15 demonstrated that peptide nanotubes (PNTs) are strongly piezoelectric with the orientation of polarization along the tube axis. Recent success in the growth of mm-sized microtubes has allowed study of not only quasistatic piezoelectric properties but also resonance phenomena. 16 Currently, it seems to be appropriate to widen the current research into organic-inorganic materials, such as amino acid and simple inorganic acid (HClO 4 , HBF 4 , etc.) derivatives. Synthesis of such a class of compounds allows us to create an almost unlimited number of new salts with potentially high piezoelectric properties. 17 Moreover, due to the presence of the chiral carbon atom of amino acids (the only exception is glycine) such a material exhibits nonlinear optical (NLO) properties. [18][19][20] The study of single crystals will allow us to correlate their structure, microstructure and functional piezoelectric properties.

Experimental
Hybrid crystals were prepared by reaction of H-b-(2-pyridyl)-Ala-OH ((S)-2-amino-3-pyridin-2-yl-propionic acid, Bachem) with either tetrafluoroboric acid (50%, POCh) or perchloric acid (60%, POCh) in water solution. The solutions were then dried under ambient conditions and yielded small, colorless, needle-shaped crystals in both cases. The PFM measurements were performed using a commercial AFM (Ntegra Prima, NT-MDT) equipped with an external function generator and a lock-in amplifier (see ref. 22 for more details). We used doped Si cantilevers with spring constants in the range of 0.35-6.1 N m À1 driven by an AC voltage of 5 V peakto-peak at a frequency of 100 kHz.
Optical microscope observations were carried out by means of a Zeiss Axioplan 2 optical microscope equipped with a Zeiss AxioCam ICc.
Crystal data, data collection and structure refinement details are summarized in Table 1. Experiments were carried out at 298 K with Mo Ka radiation using an Xcalibur, Sapphire1, long nozzle diffractometer. Data were collected in o-scan mode with Do = 1.01 using the CrysAlisCCD programme. 23 CrysAlisPRO was used for data processing. 24 Empirical absorption correction was performed using spherical harmonics, implemented in CrysAlisPRO. The structure was solved by direct methods and refined by the full-matrix least-squares method against F 2 by means of SHELXL2014/7. 25 H atoms were treated by a mixture of independent and constrained refinement. The donor H atoms from NH 3 as well as NH groups have been refined with constraints because of their proximity to librating perchlorate and BF 4 À ions. Rigid body constraints were applied to disordered  There are two protonation sites in the counterion: the amine group and the nitrogen from the pyridine ring. The first site is verified by the distance between the a-carbon and the amine nitrogen atom C(2)-N(1) of 1.481(4) Å that is characteristic of a single bond and indicates that the amine group is protonated. The latter one is validated through the C(5)-N(2)-C(4) angle of 122.61 in the pyridine ring that points to protonation of the ring nitrogen N(2). Additionally, the C-O bonds of the carboxylate group are double with lengths less than 1.252(4) Å that support the appropriate location of protonation centers. The carboxyl group is bent towards the pyridinium ring (the C(3)-C(2)-C(1)-O(6) dihedral angle is equal to À59.7(1)1). This conformation promotes the formation of an intramolecular hydrogen bond N(2)-HÁ Á ÁO (6) with a donor to acceptor distance of 2.623(4) Å and a donor to acceptor angle equal to 167(3)1.
The supramolecular assembly is controlled by numerous hydrogen bonds between the amine hydrogen atoms, CH 2 , CH groups and ClO 4 À anions. N-HÁ Á ÁO, O-HÁ Á ÁO and C-HÁ Á ÁO intermolecular interactions are crucial in building supramolecular architectures in organic-inorganic hybrids as well as metal-organic materials. [26][27][28] Oxygen from perchlorate ions acts as an acceptor in 7 different hydrogen bonds. Table 2 summarizes the hydrogen bond parameters whereas Fig. 2  Symmetry codes: (i) x + 1/2, Ày + 1/2, Àz + 2; (ii) x + 1, y, z; (iii) x, y À 1, z; They involve an amine hydrogen atom and an oxygen atom from the carboxylic group. The N1-HÁ Á ÁO5 bonds connect neighboring cations in the a direction forming infinite chains built of the C(5) motif, 29 see Fig. 2(b). Strong hydrogen bonds are also found between the protonated 3-(2-pyridyl)alanine and perchlorate oxygen atoms. They form spiral chains which propagate along the a direction and may be described by the C 1 2 (6) synthon. There are two N1-HÁ Á ÁO4 and N1-HÁ Á ÁO2 bonds within the motif, formed between the NH 3 group of protonated 3-(2-pyridyl)alanine and two perchlorate anions. The weak C-HÁ Á ÁO contacts with donor to acceptor distances ranging from 3.211 (5)     The conformation of A and B counterions is different. In A, similar to [2PyAla][ClO 4 ] the carboxylate group is bent towards the pyridinium ring and an intramolecular N(28)-HÁ Á ÁO (12) hydrogen bond is formed with a ring nitrogen serving as a donor and oxygen from the carboxylate group as an acceptor. The donor to acceptor distance equals 2.636(6) Å, and the donor to acceptor angle equals 1591. In B the side chain is more straightened and the carboxylate group is directed towards amine NH 3 from neighboring A counterions forming strong intramolecular hydrogen bonds with amine hydrogens, see Fig. 2(c) and  4 ] the strongest hydrogen bonds are formed between the 3-(2-pyridyl)alanines, between amine hydrogen atoms and oxygen from carboxylate groups. The donor to acceptor distances range from 2.743(5) to 2.826(5) Å and the angles range from 147 to 1721. They form 2D layers expanding in the a and b directions. Among them, along with the intramolecular bond and N(15)-HÁ Á ÁO(12) bonds the ring motifs may be recognized with two donor and two acceptor atoms (R 2 2 (9)). The supramolecular structure is also stabilized, especially in the c direction, by numerous N-HÁ Á ÁF interactions (see Fig. 2(d)), which are listed in Table 2. Due to the pronounced vibration motions of BF 4 À groups these hydrogen bonds are less stable. Hadži's trio. 31 It can be fit well with 3 components with the peak maximum at 2780 cm À1 , 1480 cm À1 and 1000 cm À1 in the case of [2PyAla][ClO 4 ] and 2900 cm À1 , 1500 cm À1 and 990 cm À1 for [2PyAla] [BF 4 ]. In both cases the observed images fit the asymmetric potential with a double minimum for hydrogen motion. This potential may be described using the formula: 32 V(r,R) = a 2 (R)r 2 + a 3 (R)r 3 + a 4 (R)r 4 , where r stands for the coordinate of the proton movement, R is the coordinate of the hydrogen bridge vibration and a 2 , a 3 and a 4 are R dependent parameters. The observed profiles of the trio components are caused by the coupling of the anharmonic stretching vibrations of the proton of the hydrogen bond with the hydrogen bridge vibrations, which are damped by interactions with the lattice phonons. 33 It should be emphasized that the results of IR measurements totally agree with the X-ray finding of strong, intramolecular hydrogen bonds. Table 3 presents the band frequencies and their assignments. The assignments reported in ref. [34][35][36] were used as guides. . At these temperatures the decomposition of the salts starts and up to 875 K both crystals lose about one third of the initial mass. It should be added that using the differential scanning calorimetry (DSC) technique we did not find any other phase transition in the temperature range 100-450 K. Though the thermal behavior of both studied crystals is very similar it is worth noting that the decomposition of the [2PyAla][ClO 4 ] sample is linked to an additional thermal anomaly manifested as an exoenergetic peak (at ca. 590 K). Such an effect is, however, common for perchlorate derivatives. 37,38 6 PFM measurements  4 ] sample. One can see the elongated, either needle or plate shaped, crystals. The AFM images (Fig. 5(b) and (c)) were acquired in a contact mode and the topography and out-of-plane (OOP) piezoresponse signals were recorded simultaneously (PFM -piezoresponse force microscopy, for more details see ref. 39). Fig. 5(d) shows the cross-section of the topography and piezoresponse signals of the sample taken along the lines marked in the corresponding AFM and PFM images. The dotted line intersecting the graph is the piezoresponse 0 value. It is clearly visible that the topography of the sample is strongly correlated with the piezoresponse and the microcrystals exhibit a positive (the crystal on the left) or negative signal. It is worth noting that the absolute piezoresponse either positive or negative is practically the same.  the microcrystals are needle shaped, elongated along a. The cross section of the crystals is rectangular and two other crystallographic directions, b and c, are normal to surfaces parallel to a -see Fig. S1 in the ESI. † Fig. 5(f) presents a selected microcrystal and its piezoresponse (part (g)) recorded in the plane (IP, the bottom part of the image) and OOP (the upper part of the image). The difference is striking, and one may observe only a residual OOP signal. Its magnitude is non-zero which seems to be caused by the concretion of the crystals with different orientation of molecules. The diagram below presents the piezoelectric coefficient matrix for point group 222 according to Nye. 40

Thermal behavior
In crystals belonging to the 222 point group the piezoresponse has its origin only in shear deformations. Since the concreted parts of crystals are elongated along a the OOP signal may derive either from d 25 if the electric field is parallel to b or from d 36 if the electric field is parallel to c. It is worth noting that a similar observation was made in the case of pure amino-acid crystals of H-b-(2-pyridyl)-Ala-OH. 41 It seems that the way of preparation of the sample on the substrate (see the Experimental section) may lead to the growth of non-uniform microcrystals.
In order to prove the piezoelectric character and estimate the magnitude of this effect the piezoresponse vs. AC electric field measurements were carried out. However, due to the inhomogeneous E-field distribution 42 4 ] is twice as high as that of the LNO sample. It should be noted that the recorded piezoresponse is very stable and both titled crystals can be driven under a high excitation level since neither nonlinearity nor irreversibility even at an AC voltage of 20 V was observed. The OOP response of perchlorate crystals was insignificant and was not presented in the graph.

[H-b-(2-Pyridyl)-Ala-OH][ClO 4 ]
[2PyAla][ClO 4 ] is a new peptide-based crystal. Since it crystallizes in the P2 1 2 1 2 1 space group it is a piezoelectric material. This is another amino acid derivative adopting the space group which is by far the most commonly observed crystal space group for (ordinary chiral) proteins. 45,46 One of the most interesting features besides the piezoelectricity is the spiral chains which comprise ClO 4 À oxygen atoms and protonated amino group N atoms interacting via hydrogen bonds (see Fig. 7). This arrangement resembles to some extent the structure observed in the case of L-Leu-L-Leu (LL), L-Leu-L-Phe (LF), L-Phe-L-Leu (FL), and L-Phe-L-Phe (FF). 8 The cross-section of the channel of [2PyAla][ClO 4 ] is a rectangle of dimensions ca. 5.5 Â 3.5 Å 2 , whereas the diameter of each rod (LL, FL and FF) could be roughly estimated to be in the range 17-24 Å. It was shown that the cyclic decapeptide cyclo[-(L-Trp-D-Leu) 4 -L-Gln-D-Leu-] with a 10 Å pore size (diameter) can transport glucose efficiently 47 and dynamic transport of various species was expected in the case of the above mentioned dipeptides. The channels existing in the title crystal seem to be too narrow to act as tunnels to transport other molecules but, like in the case of H-b-(2-pyridyl)-Ala-OH 41 other molecules may be expected to be incorporated into the [2PyAla][ClO 4 ] crystal as inclusions.

[H-b-(2-Pyridyl)-Ala-OH][BF 4 ]
[2PyAla] [BF 4 ] crystallizes in the polar P1 space group. The most interesting feature of this crystal is its piezoelectricity. The out-of-plane piezoelectric coefficient of the crystal response is very similar to that observed in LiNbO 3 , but the piezoelectric coefficient registered in-plane is over twice as high. This finding situates this crystal at the top of organic, amino acid based materials taking into account piezoelectric properties. The question as to why two compounds of very similar composition crystallize in two different crystallographic systems and therefore different space groups remains open. The crystal structure of salts of amino acid and their properties depend on many factors, such as: the charge state and conformation of the cation, the structure, composition and dynamical state of the anion as well as the hydrogen bond system. 48 Petrosyan 49 points out 9 different formation mechanisms on the basis of structural analysis of more than 80 salts of these amino acids. Among the salts of L-arginine there are compounds which crystallize either in the orthorhombic system (space group P2 1 2 1 2 1 ) like e.g. (L-ArgH)ClO 4 50 or in the monoclinic system (P2 1 ) like e.g. (L-ArgH 2 )(NO 3 ) 2 51 or triclinic (P1) like e.g.
(L-ArgH 2 )(ClO 4 ) 2 . 17 Another factor affecting the symmetry of the title crystals might be the strength of the acid and its influence on the charge state of the amino acid. Perchloric acid is considered as one of the strongest acids with a pK a of the order of À8 whereas tetrafluoroboric acid's pK a is À4.9 (see ref. 52) thus both acids are very strong. The hypothesis that HClO 4 fixes the structure stronger and the piezoresponse is lower than in the HBF 4 derivative is also speculative. Most probably the hydrogen bond network is crucial but the strict correlation between the hydrogen bonds and the structure remains unknown -see for example Görbitz 8 or Surekha et al. 20 It is worth noting that introduction to the building compounds of heterocyclic rings makes the hydrogen bond network stabilizing the building units more extensive. This, in turn, may produce polar properties and lead to the emergence of ferroelectricity 53 in those amino acid derivatives. It should be added that there are some recent applications based on piezoelectricity where H-bonding plays a significant role, see for instance Garain et al., 54 Jana et al., 55 Alam and Mandal 56 or Tamang et al. 57 It seems to be very promising to substitute the tetrafluoroboric or perchlorate anions either completely or partly by other inorganic anions. The number of such exchange possibilities is almost unlimited and some of them, with a high degree of possibility, may lead to crystals with desired properties -both piezoelectric and suitable for biomedical applications. The latter may be realized by using the material as a media for biologically active molecules. In this account it is not attempted to predict the suitable structures which satisfy these demands; however, it appears to be advisable to widen the scope of research into other amino acid-inorganic acid hybrid compositions.