Molecular Structure, Vibrational Spectra and Potential Energy Distribution of Colchicine Using ab Initio and Density Functional Theory

Shamoon Ahmad SIDDIQUI, Apoorva DWIVEDI, Anoop PANDEY, P. K. SINGH, Tanveer HASAN, Sudha JAIN and Neeraj MISRA


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1 Introduction

Theoretical calculations on gas phase organic molecules are an invaluable complement to experiments, whereas infrared (IR) spectroscopy studies can identify structural features occurring in the observed conformers. Comparison with computed data for the energetic and vibrational frequencies is crucial for conversion of the observed spectra into structural assignments.
Nature produces many natural products that are antibiotics, pharmacological agents or are otherwise of interest in human or animal medicine. While their purpose in nature remains obscure in most instances, they are still found to be useful for the treatment of a disease. Accordingly, it seems likely that the properties of natural products can be optimized for their projected use [1]. Colchicine (C22H25NO6) is a highly poisonous water-soluble alkaloid, originally extracted from plants of the genus Colchicum(Autumn) crocus, also known as the "Meadow saffron" [2]. Colchicine is approved by the Food and Drug Administration (FDA) for the treatment of gout and also for Familian Mediterranean fever, secondary amyloidosis (AA), and Scleroderma [3 - 7]. Its pain-relieving and anti-inflammatory effects for gout were linked to its binding with the protein tubulin. The chemical specificity of the colchicine binding site of tubulin is less stringent for the presence of the R2 ring than is the case for the R3 and R1 rings of colchicine. Consequently, the colchicine analogues with some modifications in the R2 ring bind to tubulin protein at the same receptor site as colchicine. Moreover, analogues with smaller or no substituents in the R2 ring bind to tubulin remarkably faster than colchicine [2, 8, 9].
Here, the experimental FT-IR and FT-Raman frequencies of the title molecule are compared with the theoretical frequencies obtained by ab initio Hartree-Fock and density functional B3LYP method. To gain a better understanding of the performance and limitation of HF and DFT methods, as a general approach to the vibrational problems of organic molecules, we calculated harmonic frequencies of colchicine by HF and DFT methods and compared these results with the observed fundamental vibrational frequencies. Thus the evaluation of both the methods is useful for obtaining a reliable assignment of the vibrational spectra. This study is important as a basis for further work on colchicine, in which presumably some modifications by chemical reaction such as oxidation/reduction on polyfunctional bioactive natural product may generate new reactive sites in the molecule. The aim of this study is to check the performance of ab initio Hartree-Fock and density functional B3LYP method for simulation of IR and Raman spectra of the title compound by the use of a standard 6-31G(d) basis set. To the best of our knowledge, neither the complete Raman and IR spectra nor the quantum chemical calculations for colchicine have been reported so far in the literature.

2 Experimental

The FT-IR Spectra of colchicine have been recorded in CsI on a Perkin Elmer 1800 Spectrophotometer. Spectroscopic preparations of the sample were carried out under an atmosphere of prepurified nitrogen. FT-Raman Spectra of colchicine are taken from the literature [10]. Colchicine was isolated from Colchicum autumnale [11]. The compound was identified by comparison of its IR, MS, and NMR data with those reported in the literature [12, 13]. The observed FT-IR and FT-Raman spectra of colchicine are shown in Figures 1, 2 respectively.


Figure 1. FT-IR spectra of Colchicine (4000-400) cm-1


Figure 2. FT-Raman spectra of Colchicine (4000-100) cm-1

3 Computational details

All the calculations were performed at Hartree-Fock (HF) and DFT/B3LYP level on a Pentium IV/1.66 GHZ personal computer using a Gaussian 03W [14] program package, invoking gradient geometry optimization [15]. The initial geometry generated from standard geometrical parameters was minimized without any constraint in the potential energy surface at Hartree-Fock level, adopting the standard 6-31G(d) basis set. This geometry was then re-optimized again at B3LYP level, using the basis set 6-31G(d) for better description. The optimized structural parameters were used in the vibrational frequency calculations at the HF and DFT/B3LYP levels to characterize all the stationary points as minima. We have utilized the gradient corrected density functional theory (DFT) [16] with the three-parameter hybrid functional (B3) [17] for the exchange part and the Lee-Yang-Parr (LYP) correlation function [18], accepted as a cost effective approach, for the computation of molecular structure, vibrational frequencies, and energies of optimized structures. Density functional theory offers electron correlation frequently comparable to that from second-order Moller-Plesset theory (MP2) [19, 20]. Next, the spectra were analyzed in terms of the P.E.D. contributions by using the VEDA program [21]. Finally, the calculated normal mode vibrational frequencies provide thermodynamic properties also through the principles of statistical mechanics.

4 Results and Discussion

4. 1 Geometry Optimization

The optimized structure parameters of colchicine calculated by ab initio, HF and DFT, B3LYP levels with the 6-31G(d) basis set are listed in Table 1 in accordance with the atom numbering scheme given in Figure 3. Experimental values of various bond lengths and bond angles of colchicine are taken from the literature [8]. For example, the optimized bond lengths of C-C in tropolone ring R1 fall in the range from 1.441A to 1.491A for HF and in the 1.421A-1.489A range for B3LYP method, in good agreement with the ranges of experimental bond lengths [1.405A -1.465A]; optimized bond lengths of C=C in R1 fall in the ranges 1.341A-1.345A for HF and 1.367A-1.377A for B3LYP method, also in good agreement with experimental bond lengths [1.335A-1.375A]. The optimized bond lengths of C-C in tropolone ring R2 fall in the range from 1.392A to 1.539A for HF and in the 1.409A-1.546A range for B3LYP method, also in good agreement with experimental bond lengths [1.395A-1.550A]. The optimized C-C bond lengths in benzene ring R3 fall in the range from 1.384A to 1.401A for HF and in the 1.397A-1.412A range for B3LYP method, also in excellent agreement with experimental bond lengths [1.370A -1.395A]. The other calculated bond lengths and bond angles are also in excellent agreement with experimental values. Thus, although there are some differences between the theoretical values and experimental values, the optimized structural parameters can well reproduce the experimental ones and they are the basis for the coming discussion.


Figure 3. Model molecular structure of Colchicine

4. 2 Vibrational Assignments

The molecule studied has 54 atoms and 156 normal modes of fundamental vibration. Detailed description of vibrational modes can be given by means of normal coordinate analysis. The detailed vibrational assignments are achieved by comparing the band positions and intensities observed in FT-IR and FT-Raman spectra with the wave numbers and intensities obtained from molecular modeling calculations at HF/6-31G(d) and B3LYP/6-31G(d) level. The assignments are given in Tables 2, 3.
The experimental FT-IR and FT-Raman spectra are shown in Figures 1, 2. Vibrational frequencies calculated at HF/6-31G(d) level were scaled by 0.89, and those at B3LYP/6-31G(d) level were scaled by 0.96 [22]. The descriptions concerning the assignment have also been listed in Tables 2, 3. VEDA Program [21] was used for P.E.D. analysis and for assigning the calculated harmonic frequencies.
The harmonic vibrational frequencies calculated for colchicine at HF level using basis set 6-31G(d) have been collected in Table 2 and those at B3LYP level using 6-31G(d) have been collected in Table 3. The observed FT-IR and FT-Raman frequencies for various modes of vibrations are also presented in Tables 2, 3.

4. 3 Carbonyl Absorption

Carbonyl absorptions are sensitive; both the carbon and the oxygen atoms of the carbonyl group move during the vibration and they have nearly equal amplitudes. In the present study, the C=O stretching vibrations are observed at 1660 and 1610 cm-1; such values are in agreement with the calculated frequencies obtained at 1744 and 1722 cm-1 for HF and those obtained at 1709 and 1635 cm-1 for the B3LYP method, respectively.

4. 4 N-H Vibrations

In all the heterocyclic compounds, the N-H stretching vibrations [23] occur in the region 3500-3000 cm-1. In the present study, the N-H vibration is calculated at 3454 cm-1 for HF and at 3475 cm-1 for B3LYP method, in agreement with the observed frequency obtained at 3446 cm-1. Some bending vibrations of N-H are also calculated and the values are supported by the literature [23].

4. 5 C-H Vibrations

The hetero aromatic structure shows the presence of C-H stretching vibrations in the region 3000-3100 cm-1, which is the characteristic region for the ready identification of the C-H stretching vibration [24]. In the present study the C-H stretching vibration of the title compound is observed at 3060 cm-1 in good agreement with the frequency calculated at 3023 cm-1 for HF and at 3067 cm-1 for B3LYP method. Some other C-H stretching vibrations are also calculated at 3027, 3025, 3010 and 2933 cm-1 for HF and at 3088, 3083, 3062 and 2994 cm-1 for B3LYP method; these are all supported by the literature [24]. Some bending vibrations of C-H are also calculated and are supported by the literature [24].

4. 6 Methylene Group Vibrations

The asymmetric CH2 stretching vibrations are generally observed in the region 3100-3000 cm-1, while the symmetric stretching vibrations are generally observed between 3000 and 2900 cm-1 [25]. The CH2 asymmetric stretching vibrations are calculated at 2915 and 2885 cm-1 for HF and at 2977 and 2956 cm-1 for B3LYP method, whereas CH2 symmetric stretching vibrations are also calculated at 2873 and 2857 cm-1 for HF and at 2934 and 2909 cm-1 for B3LYP method, respectively. The bands corresponding to different bending vibrations of CH2 group are summarized in Tables 2, 3 for HF and B3LYP method, respectively, and are supported by the literature [25].

4. 7 C-C Vibrations

The C-C aromatic stretching bands known as semi-circle stretching were calculated at 1644, 1632, 1600, 1572, 1527 and 1275 cm-1 for HF and at 1592, 1583, 1576, 1543, 1501 and 1275 cm-1 for B3LYP method, respectively; the values are in perfect agreement with the observed frequencies. The theoretically calculated C-C-C bending modes and C-C torsional modes have been found to be consistent with the recorded spectral values.

4. 8 Methyl Group Vibrations

The asymmetric CH3 stretching vibrations are calculated at 2970, 2965, 2964, 2963, 2962, 2961, 2937, 2920, 2914 and 2909 cm-1 for HF and at 3040, 3033, 3030, 3029, 3027, 3005, 2995, 2979, 2972 and 2965 cm-1 for B3LYP method, while symmetric CH3 stretching vibrations are calculated at 2874, 2865, 2864, 2858 and 2844 cm-1 for HF and at 2940, 2916, 2914, 2911 and 2907 cm-1 for B3LYP method. These assignments are also supported by the literature [26]. In the present study, various bending vibrations of CH3 group are also summarized in Tables 2, 3 for HF and B3LYP method and are supported by the literature [26].

4. 9 C-N Vibrations

The identification of C-N vibrations is a difficult task, since the mixing of vibrations is possible in this region. In this study, the C-N stretching vibrations are calculated at 1232, 1212 and 1103 cm-1 for HF and at 1229, 1223 and 1114 cm-1 for B3LYP method, respectively; these values are supported by the observed frequencies and the literature [27]. The various bending and torsional vibrations assigned in this study are also supported by the literature [27].

4. 10 C-O Vibrations

In this study, the C-O stretching vibrations are calculated at 1320, 1259, 1250, 1079, 1057, 1027, 1004, 983 and 923 cm-1 for HF, whereas for B3LYP method C-O stretching vibrations are calculated at 1309, 1263, 1248, 1090, 1040, 1014, 994, 979 and 916 cm-1 respectively; these values are also supported by observed spectra and literature [28]. The various bending and torsional vibrations assigned in this study are also supported by the literature [28].

Table 1. Optimized geometrical parameters of colchicine at HF/6-31G(d) & B3LYP/6-31G(d) level
S. NoParametersX-Ray dataHFB3LYP
Bond lengths (A)
1C1-O21.4451.3991.420
2C1-H301.0851.097
3C1-H311.0791.091
4C1-H321.0851.097
5O2-C31.3651.3331.348
6C3=C41.3501.3421.373
7C3-C91.4551.4911.489
8C4-C51.4051.4411.421
9C4-H331.0731.085
10C5=C61.3751.3451.377
11C5-H341.0731.085
12C6-C71.4651.4641.447
13C6-C191.4751.5051.498
14C7=C81.3351.3411.367
15C7-C111.5251.5361.542
16C8-C91.4351.4661.458
17C8-H351.0731.087
18C9=O101.2601.2001.234
19C11-N121.4551.4441.452
20C11-C161.5501.5371.543
21C11-H361.0771.092
22N12-C131.3301.3581.372
23N12-H370.9941.010
24C13-C141.5001.5131.520
25C13=O151.2201.2001.225
26C14-H381.0841.095
27C14-H391.0861.096
28C14-H401.0801.093
29C16-C171.5301.5391.546
30C16-H411.0861.097
31C16-H421.0881.099
32C17-C181.4901.5121.513
33C17-H431.0841.095
34C17-H441.0851.097
35C18-C191.3951.3921.409
36C18-C261.3951.3881.397
37C19-C201.3951.4011.412
38C20-O211.3801.3551.374
39C20-C231.3701.3881.403
40O21-C221.4001.4111.432
41C22-H451.0831.097
42C22-H461.0801.092
43C22-H471.0831.097
44C23-O241.3951.3551.369
45C23-C271.3851.3951.410
46O24-C251.4201.4081.430
47C25-H481.0851.093
48C25-H491.0811.098
49C25-H501.0801.092
50C26-C271.3951.3841.397
51C26-H511.0721.084
52C27-O281.3851.3471.366
53O28-C291.4201.4001.419
54C29-H521.0851.098
55C29-H531.0841.098
56C29-H541.0791.091
Bond angles (degree)
57O2-C1-H30111.4111.5
58O2-C1-H31105.9105.5
59O2-C1-H32111.4111.4
60H30-C1-H31109.4109.5
61H30-C1-H32109.5109.4
62H31-C1-H32109.3109.4
63C1-O2-C3119.5121.1120.1
64O2-C3=C4122.5123.7122.8
65O2-C3-C9110.0109.9109.8
66C4=C3-C9128.0126.4127.4
67C3=C4-C5130.0131.0131.0
68C3=C4-H33116.5116.1
69C5-C4-H33112.4112.9
70C4-C5=C6132.5132.4132.0
S. NoParametersX-Ray dataHFB3LYP
71C4-C5-H34112.2113.1
72C6=C5-H34115.3114.9
73C5=C6-C7123.0124.4124.5
74C5=C6-C19117.5117.0116.7
75C7-C6-C19119.5118.5118.7
76C6-C7=C8128.0127.4127.7
77C6-C7-C11113.5114.8114.9
78C8=C7-C11118.5117.8117.4
79C7=C8-C9135.0134.6135.4
80C7=C8-H35117.0116.0
81C9-C8-H35108.4108.5
82C3-C9-C8122.5122.1121.3
83C3-C9=O10119.5119.2119.2
84C8-C9=O10118.5118.6119.4
85C7-C11-N12113.5114.9114.9
86C7-C11-C16110.0110.8111.4
87C7-C11-H36107.3106.7
88N12-C11-C16109.0109.4110.1
89N12-C11-H36105.5104.9
90C16-C11-H36108.6108.4
91C11-N12-C13121.5121.8121.3
92C11-N12-H37119.0119.2
93C13-N12-H37118.6119.1
94N12-C13-C14114.5115.4115.4
95N12-C13=O15122.5122.5122.4
96C14-C13=O15123.0122.1122.1
97C13-C14-H38112.5113.6
98C13-C14-H39108.9108.9
99C13-C14-H40108.9108.8
100H38-C14-H39108.4108.5
101H38-C14-H40109.7109.3
102H39-C14-H40108.4107.6
103C11-C16-C17112.5113.1112.5
104C11-C16-H41107.9108.0
105C11-C16-H42109.5109.8
106C17-C16-H41110.0110.2
107C17-C16-H42108.8108.9
108H41-C16-H42107.4107.4
109C16-C17-C18111.0111.6111.8
110C16-C17-H43109.0109.2
111C16-C17-H44109.4108.9
112C18-C17-H43110.2110.4
113C18-C17-H44109.7109.7
114H43-C17-H44106.6106.7
115C17-C18-C19120.5119.3119.3
116C17-C18-C26120.0120.2120.5
117C19-C18-C26119.5120.4120.2
118C6-C19-C18119.5120.3120.6
119C6-C19-C20122.0121.3121.0
120C18-C19-C20118.5118.3118.4
121C19-C20-O21120.0120.3120.0
122C19-C20-C23121.5121.3121.5
123O21-C20-C23118.0118.3118.5
124C20-O21-C22116.5116.1114.3
125O21-C22-H45111.5111.5
126O21-C22-H46106.4106.1
127O21-C22-H47110.8110.9
128H45-C22-H46109.5109.6
129H45-C22-H47109.3109.3
130H46-C22-H47109.2109.2
131C20-C23-O24120.0119.1118.4
132C20-C23-C27120.0119.4119.1
133O24-C23-C27119.5121.3122.4
134C23-O24-C25116.0117.5116.9
135O24-C25-H48111.1111.7
136O24-C25-H49106.3111.0
137O24-C25-H50111.3105.7
138H48-C25-H49109.1109.4
139H48-C25-H50109.3109.7
140H49-C25-H50109.6109.2
 
 
S. NoParametersX-Ray dataHFB3LYP
141C18-C26-C27120.5120.8121.1
142C18-C26-H51118.9118.7
143C27-C26-H51120.3120.2
144C23-C27-C26119.5119.6119.6
145C23-C27-O28117.0116.1116.0
146C26-C27-O28123.5124.3124.4
147C27-O28-C29119.0119.9118.3
148O28-C29-H52111.5111.7
149O28-C29-H53111.3111.4
150O28-C29-H54106.1105.8
151H52-C29-H53109.4109.2
152H52-C29-H54109.1109.3
153H53-C29-H54109.2109.3
Dihedral angles (degree)
154H30-C1-O2-C3-59.6-59.7
155H30-C1-O2-C3-178.5-178.5
156H30-C1-O2-C362.862.8
157C1-O2-C3-C4-1.9-1.8
158C1-O2-C3-C9179.2178.8
159O2-C3-C4-C5-179.5-179.1
160O2-C3-C4-H33-1.1-0.8
161C9-C3-C4-C5-0.80.1
162C9-C3-C4-H33177.5178.5
163O2-C3-C9-C8-168.6-173.9
164O2-C3-C9=O108.84.2
165C4-C3-C9-C812.66.7
166C4-C3-C9=O10-170.0-175.2
167C3-C4-C5-C6-7.6-3.9
168C3-C4-C5-H34174.2176.8
169H33-C4-C5-C6174.0177.7
170H33-C4-C5-H34-4.2-1.6
171C4-C5-C6-C70.9-0.9
172C4-C5-C6-C19-179.8-178.7
173H34-C5-C6-C7179.0178.3
174H34-C5-C6-C19-1.7-2.0
175C5-C6-C7-C86.65.0
176C5-C6-C7-C11-176.0-176.1
177C19-C6-C7-C8-172.7-174.6
178C19-C6-C7-C114.74.2
179C5-C6-C19-C18-125.5-126.0
180C5-C6-C19-C2053.653.6
181C7-C6-C19-C1853.853.7
182C7-C6-C19-C20-127.0-126.8
183C6-C7-C8-C90.3-0.1
184C6-C7-C8-H35179.1179.9
185C11-C7-C8-C9-176.9-178.8
186C11-C7-C8-H351.81.3
187C6-C7-C11-N12156.9155.1
188C6-C7-C11-C16-78.4-78.8
189C6-C7-C11-H3640.039.3
190C8-C7-C11-N12-25.4-25.9
191C8-C7-C11-C1699.2100.2
192C8-C7-C11-H36-142.4-141.7
193C7-C8-C9-C3-12.8-7.4
194C7-C8-C9=O10169.7174.5
195H35-C8-C9-C3168.3172.5
196H35-C8-C9=O10-9.1-5.6
197C7-C11-N12-C13-82.3-83.9
198C7-C11-N12-H3788.788.8
199C16-C11-N12-C13152.3149.3
200C16-C11-N12-H37-36.7-37.9
201H36-C11-N12-C1335.632.9
202H36-C11-N12-H37-153.4-154.3
203C7-C11-C16-C1746.246.8
204C7-C11-C16-H41168.1168.7
205C7-C11-C16-H42-75.3-74.6
206N12-C11-C16-C17173.9175.5
207N12-C11-C16-H41-64.1-62.7
208N12-C11-C16-H4252.454.1
209H36-C11-C16-C17-71.4-70.3
210H36-C11-C16-H4150.651.6
S. NoParametersX-Ray dataHFB3LYP
211H36-C11-C16-H42167.1168.3
212C11-N12-C13-C14175.0176.3
213C11-N12-C13=O15-4.2-3.3
214H37-N12-C13-C144.03.5
215H37-N12-C13=O15-175.2-176.1
216N12-C13-C14-H3832.216.1
217N12-C13-C14-H39-88.0-104.9
218N12-C13-C14-H40154.0138.1
219O15=C13-C14-H38-148.6-164.3
220O15=C13-C14-H3991.374.7
221O15=C13-C14-H40-26.7-42.3
222C11-C16-C17-C1844.043.1
223C11-C16-C17-H43166.0165.6
224C11-C16-C17-H44-77.7-78.3
225H41-C16-C17-C18-76.7-77.4
226H41-C16-C17-H4345.345.0
227H41-C16-C17-H44161.6161.2
228H42-C16-C17-C18165.9165.0
229H42-C16-C17-H43-72.1-72.5
230H42-C16-C17-H4444.243.6
231C16-C17-C18-C19-70.1-69.8
232C16-C17-C18-C26107.3107.7
233H43-C17-C18-C19168.5168.4
234H43-C17-C18-C26-14.0-14.0
235H44-C17-C18-C1951.351.1
236H44-C17-C18-C26-131.2-131.3
237C17-C18-C19-C6-6.1-5.7
238C17-C18-C19-C20174.7174.7
239C26-C18-C19-C6176.4176.7
240C26-C18-C19-C20-2.8-2.9
241C17-C18-C26-C27-177.0-177.1
242C17-C18-C26-H513.83.9
243C19-C18-C26-C270.50.5
244C19-C18-C26-H51-178.8-178.6
245C6-C19-C20-O211.01.2
246C6-C19-C20-C23-176.8-177.5
247C18-C19-C20-O21-179.8-179.2
248C18-C19-C20-C232.42.1
249C19-C20-O21-C2288.191.7
250C23-C20-O21-C22-94.0-89.6
251C19-C20-C23-O24177.1177.2
252C19-C20-C23-C270.41.1
253O21-C20-C23-O24-0.8-1.5
254O21-C20-C23-C27-177.5-177.6
255C20-O21-C22-H45-55.4-55.4
256C20-O21-C22-H46-174.8-174.8
257C20-O21-C22-H4766.666.7
258C20-C23-O24-C25113.8120.6
259C27-C23-O24-C25-69.6-63.3
260C20-C23-C27-C26-2.7-3.5
261C20-C23-C27-O28177.8176.6
262O24-C23-C27-C26-179.3-179.5
263O24-C23-C27-O281.20.6
264C23-O24-C25-H48-49.0-68.4
265C23-O24-C25-H49-167.6-154.0
266C23-O24-C25-H50-173.1-172.2
267C18-C26-C27-C232.32.8
268C18-C26-C27-C28-178.2-177.4
269H51-C26-C27-C23-178.4-178.2
270H51-C26-C27-O281.01.7
271C23-C27-O28-C29-175.8-178.3
272C26-C27-O28-C294.71.8
273C27-O28-C29-H52-64.4-63.0
274C27-O28-C29-H5358.259.4
275C27-O28-C29-H54176.9178.2
 
 
 
 
 
 

Table 2. Vibrational wave numbers obtained for Colchicine at HF/6-31G(d) in cm-1, Experimental frequencies from FT-IR and FT-Raman spectra in cm-1, IR intensities (Km mol-1), Raman scattering activities (A04 amu-1) and assignment with P.E.D. in square brackets.
S. NoWave NumberExp. Freq.IR Int.RamanAssignment [P.E.D]
Unscal.Scal.I R(Raman)activity
1211951t(CNCC)R2[53]+t(CCC=O)R1[15]
2333021t(CCC=O)R1[64]
3403503t(CCCC)R1&R2[54]+
t(HCCN)adj O[15]
4474211t(CCCC)R2[51]
5514630t(CCOC)R3[43]+t(HCCN)adj O[21]
6625550t(HCCN)adj O[38]+t(CNCC)R2[13]+
t(HCCN)adj O[13]+t(CCOC)R3[12]
7675900t(CCOC)R3[51]
8726410t(CCOC)R3[61]
97869171t(CCOC)R3[60]
10938212t(CCOC)R3[49]
111099710t(COCC)R3[67]
1211410160t(CCOC)R3[45]
1313011511t(COCC)R1[52]
1414613010t(COCC)R1[48]+t(HCCN)adj O[10]
1515313624t(CCOC)R3[31]
1616114311Not defined
17179160(160)50f(CCC)R2[23]
1818116101t(HCOC)R3[73]
1921118701t(CCCO)R3[22]+f(CCC)R2[16]
2022720242Not defined
21233207111t(CCCC)R1[19]+f(CCC)R2[14]+
f(CCO)R3[11]
22244217(228)31f(CCO)R3[33]
2325022211f(CCO)R1[36]+t(HCOC)R3[13]
2427124231f(CCC)R1&R2[29]
2527724701t(HCOC)R3[18]+f(CCC)R2[12]
26295263(260)11t(HCOC)R1[74]
2731127711t(HCOC)R3[34]+t(CCCO)R3[15]
2833229622f(CCO)R1[44]
2934330511f(COC)R3[35]
30359320(325)51f(CCC)R1[18]+f(CCO)R3[13]
3137733630f(CCO)R3[38]
3238934631f(CCN)R2[41]
3340636266f(COC)R3[27]
34423376(380)41t(CCCC)R1[38]
3545840807t(OCCC)R1[37]
3646341242t(HNCC)adj O[66]
37475423(417)762f(COC)R1[18]+f(COC)R3[13]+
t(OCCC)R1[11]
38484431440254f(COC)R1[31]+t(OCCC)R1[17]
39503448(446)112f(CCC)R2[28]
40515459455365f(COC)R3[35]
41529470470265f(CC=O)R1[43]
4254848748586f(CCC)R2[33]
43557496(490)72Not defined
44579515510(510)71f(CC=O)adj N[29]+t(CCCN)[17]
45604537525(520)114f(CC=O)adj N[24]
46638568919f(NC=O)[38]+n(CC)R2[20]
47663590(595)44f(CCC)R2[30]
4868460860842t(HCC=O)adj N[54]
4972164211t(CCOC)R3[54]
5072764764f(CCO)R3[29]
5173865743f(CC=O)adj N[16]
5274166028Not defined
53769684700(700)177n(CC)R1[35]+f(CCC)R1[23]
5480171312t(CCCC)R3[25]+f(CCC)R2[10]
5582473454t(CCCC)R1&R2[36]

S. NoWave NumberExp. Freq.IR Int.RamanAssignment [P.E.D]
Unscal.Scal.I R(Raman)activity
5683674427t(O=CCC)R1[68]
5785275985t(CCCC)R3[41]
58880783781103f(CCC)R1[21]
599038041710n(CC)R3[36]
6093783461t(CCCH)R3[81]
61957852311t(HCCO)R1[78]
62973866850(835)204t(HCCC)R2[26]
63990881101n(CC)R2[52]+t(HCC=O)R1[11]
641019907905303t(HCC=O)R1[74]
651037923920132n(CO)R3[64]
66104793288t(HCCO)R1[80]
671077958017n(CC)R2[46]
681086967174t(CHCH)adj O[37]+n(CN)adj O[10]
69110097966n(CC)R2[47]
7011059839832310n(CO)R1[61]
711128100429n(CO)R3[57]
721154102710194911n(CO)R1[59]
7311621034166f(HCC)adj O[76]
741170104181Not defined
75118710571051475n(CO)R3[64]
76120010693712n(CC)R2[48]
77121210791095749n(CO)R3[61]
7812391103499n(CN)adj R2[49]+f(HCC)R2[11]
79125111139453n(CC)R1[26]+f(HCO)adj R3[10]
8012721132695f(HCO)adj R3[62]
8112851144265n(CC)R2[31]+f(HCO)adj R3[12]+
t(CHOH)adj R3[11]
821289114710013f(HCO)adj R1[88]
8312931151442f(HCO)adj R3[85]
8412941152114114f(HCO)adj R3[66]
8512951153(1150)564t(HCCC)R2[29]
86130411611910t(HCOC)R1[62]
8713241179312t(HCOC)R3[63]
8813281182556t(CHOH)adj R3[69]+
f(HCH)adj R3[11]
8913351189119593t(CHOH)adj R3[54]
9013511202642f(HCC)R2[39]
9113621212(1215)4710n(CN)adj O[12]+f(HNC)adj R2[10]
921385123229415n(CN)adj O[18]+f(HNC)adj R2[13]
93138812369319n(CC)R2[43]
941404125012539025n(CO)R1[44]+f(HCC)R1[10]
95141412597244n(CO)R1[40]+f(HCC)R1[12]+
f(HCC)R1[10]
961433127512805117n(CC)R3[38]+f(HCCC)R2[11]+
f(HCC)R2[10]
9714581298(1290)3624t(HCCC)R2[38]+n(CC)R3[23]
9814761313115f(HCC)R2[61]
99148313201322(1325)11112n(CO)R3[42]+f(HCC)R2[11]
100149813334015t(HCCC)R2[37]+f(HCC)R2[27]
1011524135713409146f(HCC)R2[57]+n(CO)R3[17]
102154013711350(1355)3757f(HCN)[58]
103155513843712f(HCH)adj N[77]
10415731400376n(CC)R3[28]+f(HCC)R1[11]
1051584141013987423f(HCC)R1[44]
106160114251425(1430)8343f(HCC)R1[29]+n(CO)R1[11]
107161314361511f(HCC)R3[71]
10816211443628f(HCH)adj N[76]
10916311452715f(HCH)adj R1[81]
11016331453426f(HCH)adj R3[75]

S. NoWave NumberExp. Freq.IR Int.RamanAssignment [P.E.D]
Unscal.Scal.I R(Raman)activity
11116341454940f(HCH)adj R3[70]
1121636145678f(HCH)R2[77]
113164114611455(1460)715f(HCH)R2[62]
11416461465116f(HCH)adj N[71]
11516481467612f(HCH)adj R3[88]
116165114691126f(HCH)adj R3[74]
117165214701217f(HCH)adj R1[90]
11816531471425f(HCH)R2[84]
11916561474911f(HCC)R3[53]+n(CC)R3[17]
120165914762619f(HCH)adj R1[74]
121166014784119f(HCH)adj R3[73]
12216691486919f(HCH)adj R3[58]
1231679149416911f(HCH)adj R3[84]
1241703151514893335f(HNC)[49]+n(NC)adj O[22]
125171615271510(1505)73997n(CC)R1[48]+f(HCC)R1[14]+
f(HCN)[10]
126176615721541(1555)3235n(CC)R3[68]
127179816001560(1572)124167n(CC)R3[59]
128183416321588255232n(CC)R1[64]+f(HCC)R1[16]
12918481644(1595)22180n(CC)R1[58]
130193517221610613129n(C=O)R1[80]
1311959174416602254n(C=O)adj N[81]
13231952844(2848)4370ns(CH3)adj R3[91]
133321028578520ns(CH2)R2[86]
1343211285825179ns(CH3)adj R1[90]
135321828642743ns(CH3)adj R3[90]
13632192865790ns(CH3)adj R3[91]
137322828738777ns(CH2)R2[90]
138322928747212ns(CH3)adj N[95]
139324228853071nas(CH2)R2[86]
140326929094868nas(CH3)adj R3[98]
141327429142938nas(CH3)adj R1[100]
142327529152940(2945)7047nas(CH2)R2[91]
143328129201950nas(CH3)adj R3[97]
1443296293310859n(C-H)R2[96]
14533012937956nas(CH3)adj R3[94]
146332729612090nas(CH3)adj N[93]
147332829624695nas(CH3)adj R3[89]
148332929631059nas(CH3)adj R3[93]
149333029641778nas(CH3)adj N[91]
1503331296538136nas(CH3)adj R3[90]
1513337297039166nas(CH3)adj R1[90]
152338230101831n(C-H)R1[99]
153339730233060650n(C-H)R1[98]
154339930251577n(C-H)R1[99]
1553401302711120n(C-H)R3[98]
1563881345434463335n(N-H)[100]
Note : Abbreviations used here have the following meaningn: stretching; ns: symmetric stretching; nas: asymmetric stretching; f: bending; t: torsion; R: Ring; adj-adjacent.

Table 3. Vibrational wave numbers obtained for Colchicine at B3LYP/6-31G(d) in cm-1, Experimental frequencies from FT-IR and FT-Raman spectra in cm-1, IR intensities (Km mol-1), Raman scattering activities (A04 amu-1) and assignment with P.E.D. in square brackets.
S. NoWave NumberExp. Freq.IR Int.RamanAssignment [P.E.D]
Unscal.Scal.I R(Raman)activity
1252403t(CNCC)R2[52]+t(CCC=O)R1[14]
2323152t(CCC=O)R1[65]
3343212t(CCCC)R1&R2[56]+
t(HCCN)adj O[12]
4403812t(CCCC)R2[50]
5484622t(CCOC)R3[44]+t(HCCN)adj O[21]
6565450t(HCCN)adj O[39]+t(CNCC)R2[13]+
t(HCCN)adj O[12]+t(CCOC)R3[12]
7595731t(CCOC)R3[50]
8666410t(CCOC)R3[62]
97269102t(CCOC)R3[63]
10888412t(CCOC)R3[49]
11979322t(COCC)R3[68]
1211110632t(CCOC)R3[44]
1312612110t(COCC)R1[51]
1414213705t(COCC)R1[47]+t(HCCN)adj O[11]
1514514025t(CCOC)R3[29]
1616315631Not defined
17170163(160)23f(CCC)R2[22]
1818217511t(HCOC)R3[75]
1919718902t(CCCO)R3[20]+f(CCC)R2[17]
2021420632Not defined
2121720881t(CCCC)R1[19]+f(CCC)R2[15]+
f(CCO)R3[10]
22229220(228)32f(CCO)R3[32]
2323122220f(CCO)R1[38]+t(HCOC)R3[11]
2425324332f(CCC)R1&R2[28]
2525524502t(HCOC)R3[16]+f(CCC)R2[13]
26272261(260)12t(HCOC)R1[75]
2728927701t(HCOC)R3[33]+t(CCCO)R3[17]
2831029732f(CCO)R1[43]
2931830501f(COC)R3[34]
30329315(325)31f(CCC)R1[17]+f(CCO)R3[12]
3134933521f(CCO)R3[39]
3236535033f(CCN)R2[40]
33381366611f(COC)R3[25]
34395379(380)32t(CCCC)R1[36]
3542140428t(OCCC)R1[37]
36432414492t(HNCC)adj O[67]
37433416(417)136f(COC)R1[16]+f(COC)R3[12]+
t(OCCC)R1[12]
384444264401913f(COC)R1[31]+t(OCCC)R1[16]
39462444(446)93f(CCC)R2[25]
40483464455198f(COC)R3[36]
41489469470326f(CC=O)R1[44]
4250248248564f(CCC)R2[33]
43519498(490)26Not defined
44535514510(510)91f(CC=O)adj N[27]+t(CCCN)[19]
45559537525(520)85f(CC=O)adj N[23]
46591567726f(NC=O)[36]+n(CC)R2[23]
47619594(595)14f(CCC)R2[28]
4863460960812t(HCC=O)adj N[55]
49653627211t(CCOC)R3[55]
5067264527f(CCO)R3[27]
5168165313f(CC=O)adj N[12]
52683656516Not defined
53718690700(700)141n(CC)R1[34]+f(CCC)R1[24]
5473370423t(CCCC)R3[23]+f(CCC)R2[11]
55747717211t(CCCC)R1&R2[35]

S. NoWave NumberExp. Freq.IR Int.RamanAssignment [P.E.D]
Unscal.Scal.I R(Raman)activity
5676072922t(O=CCC)R1[69]
5778275102t(CCCC)R3[40]
587937617811715f(CCC)R1[19]
598378031220n(CC)R3[35]
60848814191t(CCCH)R3[83]
61865830153t(HCCO)R1[79]
62872837850(835)71t(HCCC)R2[25]
6392288572n(CC)R2[53]+t(HCC=O)R1[11]
64941903905121t(HCC=O)R1[75]
65954916920102n(CO)R3[63]
6696492515t(HCCO)R1[80]
6797193376n(CC)R2[45]
6810059651013t(CHCH)adj O[38]+n(CN)adj O[11]
69101197189n(CC)R2[46]
701020979983265n(CO)R1[60]
711035994410n(CO)R3[58]
721056101410195210n(CO)R1[58]
731068102550f(HCC)adj O[77]
741079103693Not defined
75108410401051475n(CO)R3[63]
7611071063225n(CC)R2[46]
7711361090109519516n(CO)R3[64]
7811601114226n(CN)adj R2[47]+f(HCC)R2[10]
79117711304316n(CC)R1[24]+f(HCO)adj R3[12]
8011791132234f(HCO)adj R3[63]
81118011337132n(CC)R2[29]+f(HCO)adj R3[15]+
t(CHOH)adj R3[13]
821182113524f(HCO)adj R1[89]
8311841137112f(HCO)adj R3[86]
84118511381141443f(HCO)adj R3[65]
8512031155(1150)325t(HCCC)R2[28]
8612151166163t(HCOC)R1[61]
87121911701110t(HCOC)R3[65]
8812231174410t(CHOH)adj R3[70]+
f(HCH)adj R3[11]
891231118211959913t(CHOH)adj R3[55]
9012441195110f(HCC)R2[38]
9112741223(1215)8311n(CN)adj O[11]+f(HNC)adj R2[10]
92128012291033n(CN)adj O[16]+f(HNC)adj R2[14]
93129212411594n(CC)R2[44]
9413001248125336092n(CO)R1[46]+f(HCC)R1[11]
95131512632918n(CO)R1[40]+f(HCC)R1[11]+
f(HCC)R1[10]
961328127512805690n(CC)R3[39]+t(HCCC)R2[12]+
f(HCC)R2[10]
971336 1282(1290)2312t(HCCC)R2[39]+n(CC)R3[22]
98135713021215f(HCC)R2[60]
99136413091322(1325)136124n(CO)R3[43]+f(HCC)R2[10]
100136513111318t(HCCC)R2[36]+f(HCC)R2[28]
1011391133613408692f(HCC)R2[58]+n(CO)R3[16]
102141613591350(1355)2943f(HCN)[57]
103142613694321f(HCH)adj N[79]
104144213857412n(CC)R3[26]+f(HCC)R1[12]
10514531395139821142f(HCC)R1[46]
106147514161425(1430)6075f(HCC)R1[27]+n(CO)R1[10]
107148614275354f(HCC)R3[72]
108149814382013f(HCH)adj N[79]
10915011441647f(HCH)adj R1[82]
1101504144428f(HCH)adj R3[76]

S. NoWave NumberExp. Freq.IR Int.RamanAssignment [P.E.D]
Unscal.Scal.I R(Raman)activity
111151014491123f(HCH)adj R3[71]
11215141453323f(HCH)R2[79]
113151514541455(1460)1620f(HCH)R2[61]
11415161455520f(HCH)adj N[70]
11515201459930f(HCH)adj R3[90]
11615211460721f(HCH)adj R3[75]
11715241463832f(HCH)adj R1[91]
11815261465821f(HCH)R2[85]
119152914681368f(HCC)R3[52]+n(CC)R3[18]
120153014693339f(HCH)adj R1[76]
12115341472188f(HCH)adj R3[74]
122153714762340f(HCH)adj R3[57]
12315431482624f(HCH)adj R3[85]
1241544148314892473f(HNC)[47]+n(NC)adj O[23]
125156415011510(1505)41666n(CC)R1[49]+f(HCC)R1[12]+
f(HCN)[10]
126160815431541(1555)1046n(CC)R3[67]
127164215761560(1572)111658n(CC)R3[58]
128164915831588210186n(CC)R1[65]+f(HCC)R1[15]
12916581592(1595)45211n(CC)R1[59]
13017031635161035335n(C=O)R1[81]
1311780170916601675n(C=O)adj N[83]
13230282907(2848)64102ns(CH3)adj R3[90]
133303029094486ns(CH2)R2[87]
1343032291159163ns(CH3)adj R1[91]
1353035291487ns(CH3)adj R3[91]
1363038291690198ns(CH3)adj R3[93]
1373056293423123ns(CH2)R2[91]
138306329408118ns(CH3)adj N[97]
139307929562174nas(CH2)R2[87]
140308929653955nas(CH3)adj R3[99]
141309529723457nas(CH3)adj R1[100]
142310129772940(2945)3378nas(CH2)R2[90]
143310329793935nas(CH3)adj R3[98]
14431192994647n(C-H)R2[95]
145312029954776nas(CH3)adj R3[93]
146313030051450nas(CH3)adj N[94]
147315330272388nas(CH3)adj R3[88]
1483155302923116nas(CH3)adj R3[94]
14931563030984nas(CH3)adj N[90]
1503159303328168nas(CH3)adj R3[91]
1513166304025189nas(CH3)adj R1[91]
15231903062673n(C-H)R1[100]
1533195306730601539n(C-H)R1[99]
154321230839105n(C-H)R1[99]
155321730881387n(C-H)R3[99]
1563620347534461752n(N-H)[100]
Note : Abbreviations used here have the following meaningn: stretching; ns: symmetric stretching; nas: asymmetric stretching; f: bending; t: torsion; R: Ring; adj: adjacent.

5 Conclusion

The equilibrium geometries and harmonic frequencies of colchicine were determined and analyzed at both HF and DFT level of theories. The vibrational frequency calculation proved that the structure is stable (no imaginary frequencies). The difference between the observed and scaled wave number values of most of the fundamentals is very small. Any discrepancy noted between the observed and calculated frequencies may be due to the fact that the calculations have been actually done on a single molecule in the gaseous state contrary to the experimental values recorded in the presence of intermolecular interactions. The potential energy distribution contribution to each of the observed frequency values shows the reliability and accuracy of the normal mode analysis. The normal mode analysis of colchicine opens up an avenue for further conformational research. With the continuing need for novel structures and the difficulty of gaining access to large tracts of bio diversity in habitats, combinatorial chemistry blended with modern quantum chemical methods can prove to be a blessing for the researchers.

The authors wish to acknowledge the Muslim Association for the Advancement of Science "MAAS", Aligarh, for providing financial support to them.

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