Infrared and Raman Spectra of Histamine-Nh 4 and Histamine-Nd 4 Monohydrochlorides

JOURNAL OF RAMAN SPECTROSCOPY J. Raman Spectrosc. 30, 391 397 (1999) Infrared and Raman Spectra of Histamine-Nh 4 and Histamine-Nd 4 Monohydrochlorides J. A. Collado and F. J. Ramírez* Departamento de Química Física, Facultad de Ciencias, Universidad de Málaga, 29071-Málaga, Spain The infrared and Raman spectra of histamine monohydrochloride and its N -deuterated derivative as solid samples were recorded. The data obtained were analyzed from the crystal structure. A general assignment of the fundamental vibrational modes was proposed on the basis of the measured isotopic shifts and correlations with previous data reported for imidazole and related molecules. The results are consistent with the interactions between adjacent molecules present in solid state. Copyright 1999 John Wiley & Sons, Ltd. INTRODUCTION Histamine (2-aminoethylimidazole) is a chemical messenger widely distributed in plants, bacteria, insects and superior animals. 1 It is involved in several complex biological processes in which it interacts with specific receptors on the cell membranes. 2,3 Histamine stimulates many muscles to contract, which in some cases gives rise to vasodilation and a fall in blood pressure, as a part of the body s defense mechanism. 4 The relationship between histamine and allergies has been clearly established, as histamine is released when the body is invaded by external agents (drugs, proteins, etc.). Other physiological functions of histamine are related to stomach secretions, heart stimulation, inmunological reactions, etc. 2 Structurally, histamine free base is composed of an imidazole ring with an aminoethyl side-chain. Both the imidazole and aminoethyl moieties can accept a proton to give successively histamine monocation and dication (Fig. 1). Thus, the ph of the medium and the two pks of histamine 5 determine the ratios among these three ionic species. At extremely basic ph histamine rejects its imidazoleattached hydrogen giving the anion. At physiological ph (around 7.4), the predominant species is the monocation (96%); however, the ph at the sites of action of histamine 6 could be lower (ca 6.0), and a significant population (40% or more) of the dication would be considered. On the other hand, both the free base and monocation can exist as two different tautomers, as displayed in Fig. 1. Therefore, histamine is a dynamic molecule, and all the ionic and tautomeric species have different properties with different biological activities. The knowledge of these properties is essential in order to understand the biological roles of histamine. In this paper, we report a vibrational analysis of solid histamine monohydrochloride, His C -Nh 4, and its deuterated derivative (Nd 4 ), in relation to the crystal structure. * Correspondence to: F. J. Ramírez, Departamento de Química Física, Facultad de Ciencias, Universidad de Málaga, 29071-Málaga, Spain. E-mail: ramirez@uma.e Contract/grant sponsor: Junta de Andalucia; Contract/grant number: FQM159. This study is part of more extensive work aimed at analyzing the interactions between biogenic amines and nucleic acids by vibrational spectroscopy, in which we are trying to answer some questions about metabolic interplay and coincident biological effects between histamine and ornithine-derived polyamines. 7 Prior to this work, the infrared spectra of the solid monocation was reported by Bellocq et al., 8 proposing a first assignment for some bands. Since that report, no others articles have been found in the literature about vibrational studies of histamine monocation, in spite of its biological significance. In this paper we present a comprenhensive vibrational study of His C -Nh 4 and His C -Nd 4 from their Fourier transform infrared (FT-IR) and Raman (FT-Raman) spectra. They were analyzed in order to propose a general assignment of the fundamental vibrations of this molecule. The results will be a great aid in further studies on the interaction of histamine and biological macromolecules. EXPERIMENTAL FT-IR and FT-Raman spectra were recorded with a Bruker Equinox 55 Fourier transform spectrometer. FT-IR spectra were obtained from potassium bromide pellets and FT- Raman spectra from microcrystalline powders. Samples were always manipulated in a sealed box purged with dried nitrogen gas, while the spectrometer were purged with argon gas. Excitation was effected with radiation of 1064 nm from an Nd : YAG laser working at 1 W. A minimum of 500 scans were accumulated for all the spectra, the best resolution being 2 cm 1. Histamine monohydrochloride was synthesized by mixing equimolecular amounts of histamine free base (supplied by Aldrich) and hydrogen chloride in solution, followed by evaporation in a desiccator during several days. The N-deuterated isotopomer was prepared by lyophilizing the natural derivative twice from D 2 O (99.9% D, Aldrich). Both syntheses were followed by Raman spectroscopy. The purity of the natural derivative was checked from the complete disappearance of the two characteristic N H amine stretching vibrations of histamine free base, up to 3300 cm 1. The hydrogen deuterium interchange ratio CCC 0377 0486/99/050391 07 $17.50 Received 19 November 1998 Copyright 1999 John Wiley & Sons, Ltd. Accepted 20 January 1999

392 J. A COLLADO AND F. J RAMÍREZ was checked by following the N D ammonium stretching vibrations, around 2300 cm 1, and can be considered almost complete, as can be observed in its Raman spectrum. In the infrared spectrum, nevertheless, bands from the nondeuterated or partially deuterated molecule can be weakly observed, indicating that some H D interchange occurs during the registration and/or preparation procedures, in which contact with the air cannot be avoided. RESULTS AND DISCUSSION Figure 1. Tautomeric and ionic equilibria for the histamine molecule. The structure of His C in the solid state has been investigated by diffraction techniques with the monohydrobromide. 9 The unit cell contains four molecules with independent histamine cations and bromide anions. No crystal field splittings have been observed in the vibrational spectra, therefore the assignments have been proposed for the molecular unit. A molecule of histamine monocation is composed of 18 atoms, so it has 48 normal vibrational modes. Because no symmetry elements exist in a simple molecule of these species, all the vibrations are infrared and Raman active. To assign the spectra, we have defined a set of locally symmetrized modes 10 that can be easily correlated with characteristic group wavenumbers. The infrared spectra of histamine monohydrochloride and its N-deuterated derivative are displayed in Figs 2 and 3, respectively, Figure 2. FT-IR spectrum of natural histamine monohydrochloride in potassium bromide pellets. Figure 3. FT-IR spectrum of N-deuterated histamine monohydrochloride in potassium bromide pellets.

IR AND RAMAN SPECTRA OF HISTAMINE MONOHYDROCHLORIDES 393 Figure 4. FT-Raman spectrum of natural histamine monohydrochloride as a microcrystalline powder. Figure 5. FT-Raman spectrum of N-deuterated histamine monohydrochloride as a microcrystalline powder. and the corresponding Raman spectra in Figs 4 and 5, respectively. Results for measured wavenumbers, relative intensities and proposed assignments are summarized in Tables 1 3. The assignments were based on the isotopic shifts upon deuteration and on correlations with previous work on related molecules such as as imidazole derivatives. According to the tables, the assignments are discussed in three sections, namely a high-wavenumber region (3500 2000 cm 1 ), a medium-wavenumber region (2000 1000 cm 1 ) and a low-wavenumber region (below 1000 cm 1 ). High-wavenumber region (3500 2000 cm 1 ) Assignments to the bands measured in this region are summarized in Table 1. They involve the stretching vibrations for nitrogen hydrogen and carbon hydrogen bonds, which can be discriminated from the spectra of the deuterated derivative. The wavenumbers of the C H stretching vibrations are fairly stable, whereas those of the N H stretching vibration are significantly environmentdependent. The molecular structure obtained in the solid state, 9 displayed in Fig. 6, corresponds to the N H tautomeric form; the cations are linked by linear intermolecular hydrogen bonds which involve an ammonium-attached hydrogen and the non-protonated imidazolic nitrogen, N. This interaction gives rise to a very intense, broad band Table 1. Experimental wavenumbers and relative intensities a in the vibrational spectra of histamine monohydrochloride and its N -deuterated derivative in the 3500 2000 cm 1 region His C -NH4 His C -ND4 FT-IR FT-Raman FT-IR FT-Raman Q/cm 1 1Q/cm 1 Q/cm 1 1Q/cm 1 Assignment b 3180 vs as NH 3C 3149 w 3150 m 3146 sh 3147 m (CH) 3143 sh as NH 3C 3104 s 3110 vs 3107 s 3108 vs (CH) 3093 s s NH 3C 2984 w 2988 m 2984 w 2988 s CH 2 2968 sh 2971 m (NH) 2942 w 2946 s 2942 w 2946 s CH 2 2936 w 2935 s 2936 w 2935 s CH 2 2917 sh 2919 vs 2917 sh 2919 vs CH 2 2360 vs 2355 vs as ND 3C 2288 s 2283 w as ND 3C 2249 s 2243 w s ND 3C 2204 s 2205 m (ND) a w D Weak; m D medium; s D strong; v D very; sh D shoulder. b D stretching; as D antisymmetric; s D symmetric. between 3500 and 2700 cm 1 in the infrared spectrum of solid histamine monocation. This band makes the rest of the absorptions in this region, (NH 3C ), (CH 2 ) and

394 J. A COLLADO AND F. J RAMÍREZ Table 2. Experimental wavenumbers and relative intensities a in the vibrational spectra of histamine monohydrochloride and its N -deuterated derivative in the 2000 1000 cm 1 region His C -NH4 His C -ND4 FT-IR FT-Raman FT-IR FT-Raman Q/cm 1 1Q/cm 1 Q/cm 1 1Q/cm 1 Assignment b 1622 m υ as NH 3C 1599 w 1602 w υ as NH 3C 1570 m 1569 m 1562 m 1562 s (ring) 1487 m 1487 m (ring) 1475 m 1479 sh 1473 m 1476 m (ring) 1458 m 1460 m υ s NH 3C 1455 m 1450 m 1458 m 1450 m υ CH 2 1441 w 1441 m υ CH 2 1385 w-m 1387 w 1372 m 1372 m (ring) 1334 sh 1335 sh ω CH 2 1320 m-s 1324 vs 1321 w 1322 vs ω CH 2 1298 m 1301 m (ring), deut. 1279 w-m 1274 s 1262 w 1260 s t(ch 2 ) 1252 sh 1255 w 1255 m 1252 sh υ(ch) 1246 m-s 1246 w υ(nh) 1224 s 1230 m 1212 m 1215 w t(ch 2 ) 1236 m 1233 m υ as ND 3C 1163 sh 1165 m r(nh 3C ) 1160 sh 1161 w υ as ND 3C 1150 s 1152 m 1152 s 1147 w (ring) 1090 s 1095 vs υ s ND 3C 1093 m 1093 m 1076 w 1075 m υ CH 1076 s 1079 w 1044 w 1046 m (CX) 1023 m 1028 m 1006 m 1005 m (CN) a w D Weak; m D medium; s D strong; v D very; sh D shoulder. b D stretching; υ D in-plane bending (imidazole ring) or bending (side-chain); ω D wagging; t D twisting; r D rocking; as D antisymmetric; s D symmetric. (CH) (see footnotes of Table 1), appear as weaks bands or shoulders. In the Raman spectra the activity of the fundamentals is much greater than any others vibrational transitions, 11 and as a consequence the spectra in this region (Fig. 4) are very clear, which allows for a more precise measurement of the band maxima. The capture of a proton by the amino group of histamine free base did not produce bands at wavenumbers higher than 3200 cm 1, where the characteristic (NH 2 ) bands usually appear. 12 Instead, new bands between 3200 and 3000 cm 1 can be observed, corresponding to the (NH 3C ) vibrations. The infrared spectrum of His C -Nh 4 exhibes two broad absorptions upon the very intense N H band, centered at 3180 and 3093 cm 1. They do not appear in the infrared spectrum of the deuterated sample, thus Figure 6. Molecular structure of histamine monocation in a unit cell of its monohydrobromide. Table 3. Experimental wavenumbers and relative intensities a in the vibrational spectra of histamine monohydrochloride and its N -deuterated derivative in the 1000 200 cm 1 region His C -NH4 His C -ND4 FT-IR FT-Raman FT-IR FT-Raman Q/cm 1 1Q/cm 1 Q/cm 1 1Q/cm 1 Assignment b 989 s 989 s 962 m-s 969 s (CH) 962 s 961 w-m (NH) 946 m 950 w υ(nd) 940 s 944 m 914 w 915 m υ(ring) 933 sh 933 m 891 w 894 w r(ch 2 ) 856 w-m 859 w υ(ring) 848 m 850 w-m 847 m-s 850 w (CC) 823 w 823 w υ(ring), deut. 810 w 809 w r(nd 3C ) 764 s 770 w-m 750 sh 754 w (CH) 740 m 741 m 732 s 732 w r(ch 2 ) 681 m-s 677 m-s 668 w 674 m (ring) 623 s 629 m 586 m 582 w (ring) 625 s 632 m (ND) 501 w 506 w (NH 3C 375 w 371 w υ(skel) 359 w 353 w υ(skel) 328 w (ND 3C a w D Weak; m D medium; s D strong; v D very; sh D shoulder. b D stretching; υ D in-plane bending (imidazole ring) or bending (side-chain); D out-of-plane bending; D torsion; r D rocking; skel D skeletal side-chain. supporting their assignment as NH 3C vibrations, antisymmetric and symmetric, respectively. The Raman spectrum does not allow the measurement of these peaks, because of the close strong C H stretching vibrations from the imidazole ring. However, a clear shoulder on the intense Raman band at 3150 cm 1 can be observed for His C -Nh 4, which disappears upon deuteration. This was measured at 3143 cm 1, and assigned as the second antisymmetric NH 3C stretching vibration, on the basis of the local symmetry of the ammonium group. These assignments can be supported by vibrational studies on other ammoniumcontaining molecules in the solid state, such as amino acids. For example, they have been assigned at 3152 and 3058 for glycine 13 and at 3140 and 3077 cm 1 for aspartic acid. 14 The low wavenumber measured for one of the (NH 3C is consistent with the crystal structure observed for histamine monocation, 9 discussed previously, in which the intermolecular interactions involve one ammonium hydrogen. Although no data for interatomic distances between adjacent cations have been reported, the differences with respect to the others (NH 3C wavenumbers indicate that these interactions could also affect the two non-attached hydrogens. The strong bands observed in the Raman spectrum of His C -Nh 4 at 3148 and 3109 cm 1 have been assigned to the two (CH) of the imidazole ring. They correlate well with the wavenumbers proposed for the same vibrations in solid imidazole, 15,16 at 3145 and 3125 cm 1. In the infrared spectrum two weak peaks were measured at 3150 and 3104 cm 1, in good correlation with the Raman bands. The spectra of His C -Nd 4 also shows these bands, without appreciable intensity decreases or wavenumber shifts. Comparing the spectra in Figs 4 and 5 between 2800 and 3000 cm 1, a band at 2971 cm 1 almost disappears on deuteration, whereas the rest of the bands remain

IR AND RAMAN SPECTRA OF HISTAMINE MONOHYDROCHLORIDES 395 unchanged. This confirms its assignment to the (NH) of the imidazole ring. The presence of a small shoulder at the same wavenumber in the Raman spectra of the deuterated derivative indicates partial deuteration, even in the Raman spectrum. It has been proved 17 that the kinetics of the hydrogen deuterium interchange are very fast for an ammonium group, but not for N-attached imidazole hydrogens. In the infrared spectrum of histamine dihydrochloride a weak band having the same behavior upon deuteration can be measured at 2968 cm 1, confirming this assignment. On both sides of the (NH) Raman band, the main maxima at 2988, 2946, 2935 and 2819 cm 1 have been assigned to the four (CH 2 ) fundamental vibrations of the His C -Nh 4 side-chain, in which we expect vibrations from the two methylene groups to be strongly coupled, because of their proximity. These vibrations are observed in the IR spectra as weak bands, namely at 2984, 2942, 2936 and 2917 cm 1. Finally, the infrared and Raman spectra of His C -Nd 4 show new bands between 2200 and 2400 cm 1 corresponding to the nitrogen deuterium stretching vibrations. Infrared bands at 2360, 2288, 2249 and 2204 cm 1 were measured, while the Raman spectrum exhibits two clear maxima at 2355 and 2205 cm 1 joined to other less intense bands. In correlation with the proposed assignments for the natural derivative, the (ND 3C ) vibrations have been assigned to the three highest wavenumbers and the (ND) mode to the infrared band at 2204 cm 1. Medium-wavenumber region (2000 1000 cm 1 ) The measured wavenumbers, relative intensities and proposed assignments for the bands observed in this region are summarized in Table 2. The ammonium group gives rise to one or two vibrations around 1600 cm 1 which correspond to the antisymmetric bending modes. The Raman spectrum of His C -Nh 4 shows a band at 1602 cm 1 which disappears for His C -Nd 4 ; a similar behavior is observed in the infrared spectra for the bands measured at 1622 and 1599 cm 1 for the natural derivative, although in this case the bands do not completely disappear because of partial deuteration as a consequence of the sample preparation. We have assigned all of these bands to the antisymmetric NH 3C bending vibrations. Near to the υ(nh 3C ) bands, a more intense Raman peak is measured at 1569 cm 1 for His C -Nh 4 and at 1562 cm 1 for His C -Nd 4. The measured downward shift is8cm 1, and it indicates some contribution of hydrogen involved vibrations in the normal mode. Taking into account the molecular disposal of the histamine monocation in the crystal, 9 this band could correspond to an imidazole stretching vibration, the observed shift being a consequence of the interaction between two adjacent molecules. On the other hand, Hodgson et al. 15 assigned the higher wavenumber (ring) in solid imidazole at 1541 cm 1, and previous workers 18,19 proposed that this band has some υ(nh) character. All of these data confirm that this band can be assigned largely to a (ring) vibration. Partial deuterium interchange is observed for this band in the infrared spectrum of His C -Nd 4,wherea remaining peak at 1570 cm 1 appears together to the main absorption at 1562 cm 1. Raman bands at 1487, 1479 and 1460 cm 1 were measured that correspond to the infrared peaks at 1487, 1475 and 1458 cm 1. From the spectra of solid imidazole two of these wavenumbers have to be assigned as (ring) stretching modes. Thus, Perchard et al. 18 assigned them at 1485 and 1446 cm 1 ; they also proposed the bands at 1425 and 1338 cm 1 for the same vibrations of the N- deuterated derivative. These assignments were supported by Hodgson et al. 15 For histamine monocation, a third band has to be expected to appear here, which could correspond to the symmetric bending vibration to the ammonium group, υ s NH 3C. The Raman spectrum of His C -Nd 4 only shows a band between 1460 and 1500 cm 1, measured at 1476 cm 1, while a new band is observed at 1301 cm 1 which appears in the infrared spectrum at 1298 cm 1. On the basis of these facts, the bands at 1487 and 1458 cm 1 have been assigned to stretching vibrations of the imidazole ring, (ring), while the band at 1475 cm 1 has been assigned to the υ s NH 3C mode. The related (ring) vibrations for His C -Nd 4 were assigned at 1473 and 1301 cm 1 in the Raman spectrum. The high isotopic shift observed for the second (ring) indicates that the interaction between the (ring) and NH or NH 3C bending modes is stronger than for the two (ring) previously assigned at 1569 and 1487 cm 1. The proximity of the υ s NH 3C eigenvalue could explain the strong coupling, because no symmetry restrictions can be applied for this molecule; however, we cannot discard the υ NH being involved in the normal coordinate, as has been proposed by several workers. 20 In addition, the ammonium groups and the imidazole rings are linked by hydrogen bonds in the crystal, 9 as has been mentioned earlier, thus supporting this hypothesis. Near these bands, the methylene bending modes have been assigned at 1455 and 1441 cm 1 in the infrared spectra of His C -Nh 4, and appear at close wavenumbers on deuteration. In the Raman spectrum, only the component at 1450 cm 1 was observed. The infrared spectrum of His C -Nh 4 shows three bands between 1400 and 1300 cm 1, namely at 1385, 1334 and 1320 cm 1 ; all of them have been also measured in the Raman spectrum at similar wavenumbers. The band at 1385 cm 1 shifts by 13 cm 1 upon deuteration; this is in the range of the observed shifts for the (ring) vibration. The other two bands do not shift appreciably and have been assigned to CH 2 wagging vibrations. Two bands can be observed in the infrared spectrum of imidazole between 1300 and 1200 cm 1, around 1260 and 1240 cm 1. They have been assigned by several workers to υ(ch) and υ(nh) in-plane bending vibrations, respectively. 15,18,19 For His C -Nh 4, they appear together with the methylene twisting modes, t(ch 2 ). This gives rise to four infrared absorptions, namely at 1279, 1252, 1246 and 1224 cm 1, all of them also observed in the Raman spectrum as listed in Table 2. One of these, that measured at 1246 cm 1, disappears in the spectra of His C - Nd 4, and consequently has been assigned to the υ(nh) vibration. Bands at 1279 and 1224 cm 1 shift downwards by about 15 cm 1 upon deuteration in both the infrared and Raman spectra, whereas the band at 1252 cm 1 does not change appreciably. Taking into account that the methylene bending vibrations should involve some displacement of the ammonium group, small shifts can be justified in the spectra of the N-deuterated derivative, so the two first wavenumbers have been assigned to t(ch 2 ) vibrations and the υ(ch) mode was assigned at 1252 cm 1.

396 J. A COLLADO AND F. J RAMÍREZ New bands arise in the Raman spectrum of the N- deuterated derivative at 1233, 1161 and 1095 cm 1.They were confirmed in the infrared spectrum, where bands at 1236, 1160 and 1090 cm 1 were measured. They are within the usual range for υ(nd 3C ) vibrations of deuterated primary amine hydrochlorides, 12 and can be well correlated with studies on amino acids. 13,14,21 Near them, the medium intensity band measured at 1163 cm 1 in the Raman spectrum of His C -Nh 4 was assigned to an ammonium rocking vibration, r(nh 3C ). In addition, the last (ring) was assigned at 1152 cm 1 for His C -Nh 4 and at 1147 cm 1 for the deuterated derivative; this isotopic shift is in agreement with the prior assignments proposed in the present paper for the same vibrations. Between 1100 and 1000 cm 1 we can observe three bands in the Raman spectrum of His C -Nh 4, namely at 1093, 1079 and 1023. They shift downwards by 17, 35 and 22 cm 1, respectively, for His C -Nd 4. For solid imidazole only two bands have been reported in this region, and they have been unequivocally assigned to υ(ch) vibrations. 15 In our case, one C H bond is replaced by a C X bond, where X is the side-chain, its related vibrations going to lower wavenumbers. Thus the three aforementioned bands observed for histamine hydrochloride were assigned to the υ(ch), (CX) and (CN) vibrations. The relatively elevated shifts measured for all of them indicate, as expected, significant displacements of some nitrogenattached hydrogens in their normal coordinates, which will be a systematic behavior for the rest of the bands observed in the vibrational spectra. Low-wavenumber region (1000 200 cm 1 ) Table 3 gives the wavenumbers and assignments proposed below 1000 cm 1 for histamine monohydrochloride. As mentioned earlier, most of them show significant shifts upon deuteration. This is easily observed in the infrared and Raman spectra, and is due to the large mixing among the vibrational coordinates. Therefore, bands can be only approximately assigned to a simple vibration. The analysis was carried out in two steps: first, characteristic vibrations of the imidazole ring were assigned by comparison with previous work on solid imidazole, and second, we assigned the vibrations of the side-chain. The two (CH) out-of-plane vibrations were assigned at 989 and 764 cm 1 in the infrared spectrum of His C - Nh 4, and at 962 and 750 cm 1 for His C -Nd 4. As described for aromatic heterocycles, they correspond to intense infrared absorptions. 12 The (NH) vibration was assigned at 961 cm 1 ; this band disappears in the Raman spectrum of the deuterated derivative, where the corresponding (ND) vibration was assigned to a new band at 625 cm 1. The in-plane and out-of-plane bending vibrations of the imidazole ring, υ(ring) and (ring), were assigned from correlations with previous assignments proposed for solid imidazole, 934, 894, 657 and 619 cm 1 from Ref. 15. As can be seen in Table 3, they correlate well with the wavenumbers measured in this work, namely 940, 856, 681 and 623 cm 1. Concerning the side-chain, the methylene rocking and skeletal stretching vibrations were assigned between 700 and 1000 cm 1, while the skeletal bending modes give rise to several bands below 400 cm 1. We included as skeletal bending modes the in-plane and out-of-plane imidazole side-chain vibrations, because we expect them to be extensively coupled. Some of them were recorded in the Raman spectra, as listed in the Table 3, showing isotopic shifts of several cm 1. Finally, the Raman spectrum of His C -Nh 4 showed a weak band at 506 cm 1,whichwas measured at 501 cm 1 in the infrared spectrum. They were not observed for the N-deuterated derivative, so they were both assigned to the ammonium torsional vibration. The related ND 3C vibration was assigned to a new band at 328 cm 1 observed in the Raman spectrum of His C -Nd 4. The relatively high wavenumber of these vibrations is due to the intermolecular interactions involving the NH 3C moieties of histamine monocation. CONCLUSIONS The infrared and Raman spectra of histamine monohydrochloride and its N-deuterated derivative were recorded in the solid state. A general assignment for the fundamental vibrations of these molecules was proposed on the basis of the isotopic shifts and correlations with similar molecules. The results are discussed in relation to the crystal structure observed for the monohydrobromide, and are completely consistent with linkages by hydrogen bonds that involve adjacent cations in the unit cells. 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