CD/UV spectrum analysis
Dexmedetomidine is a medetomidine activator (D-form) having an imidazole skeleton and is a high central α2 adrenaline receptor agonist with high strength and selectivity. It inhibits stimulus transfer of the sympathetic nerve by stimulating the central nerve a2 receptor and has a sedative effect. Furthermore, this molecule has the simplest optical activity.
This section explains how to perform CD/UV spectrum calculation using the dexmedetomidine molecule.
Structural formula of dexmedetomidine: Precedex®
![Precedex](images/cduv_dex.png)
Structure data of dexmedetomidine (R-form) (Dexmedetomidine.mol)
Dexmedetomidine 31 32 0 0 0 1 V2000 -1.0778 -1.6715 0.6897 C 0 0 0 0 0 -2.0603 -2.6647 1.0836 N 0 0 0 0 0 -2.4168 -2.2186 2.4226 C 0 0 0 0 0 -1.8248 -1.1779 2.8306 N 0 0 0 0 0 -0.9540 -0.8156 1.7107 C 0 0 0 0 0 -0.0612 0.3840 1.7794 C 0 0 0 0 0 0.6530 0.5305 0.4721 C 0 0 0 0 0 1.6443 -0.4148 0.0972 C 0 0 0 0 0 2.3211 -0.2864 -1.1434 C 0 0 0 0 0 2.0041 0.7900 -2.0119 C 0 0 0 0 0 1.0134 1.7374 -1.6414 C 0 0 0 0 0 0.3382 1.6082 -0.3982 C 0 0 0 0 0 -0.8947 1.6284 2.0582 C 0 0 0 0 0 -0.7060 2.6067 -0.0050 C 0 0 0 0 0 0.6790 2.8690 -2.5617 C 0 0 0 0 0 -0.5680 -1.6802 -0.2851 H 0 0 0 0 0 -1.9104 -3.6810 0.8775 H 0 0 0 0 0 -3.1582 -2.7716 3.0179 H 0 0 0 0 0 0.6828 0.2465 2.5956 H 0 0 0 0 0 1.8873 -1.2500 0.7705 H 0 0 0 0 0 3.0881 -1.0203 -1.4318 H 0 0 0 0 0 2.5261 0.8903 -2.9749 H 0 0 0 0 0 -0.9541 1.8063 3.1554 H 0 0 0 0 0 -1.9247 1.4948 1.6581 H 0 0 0 0 0 -0.4306 2.5163 1.5733 H 0 0 0 0 0 -1.1426 2.3320 0.9812 H 0 0 0 0 0 -0.2528 3.6205 0.0707 H 0 0 0 0 0 -1.5176 2.6296 -0.7662 H 0 0 0 0 0 -0.1300 3.4917 -2.1188 H 0 0 0 0 0 1.5781 3.5043 -2.7251 H 0 0 0 0 0 0.3338 2.4705 -3.5419 H 0 0 0 0 0 1 2 1 0 0 0 1 5 2 0 0 0 1 16 1 6 0 0 2 3 1 1 0 0 2 17 1 0 0 0 3 4 2 0 0 0 3 18 1 1 0 0 4 5 1 6 0 0 5 6 1 0 0 0 6 7 1 6 0 0 6 13 1 0 0 0 6 19 1 1 0 0 7 8 2 0 0 0 7 12 1 6 0 0 8 9 1 6 0 0 8 20 1 1 0 0 9 10 2 0 0 0 9 21 1 0 0 0 10 11 1 0 0 0 10 22 1 6 0 0 11 12 2 0 0 0 11 15 1 6 0 0 12 14 1 0 0 0 13 23 1 1 0 0 13 24 1 0 0 0 13 25 1 0 0 0 14 26 1 1 0 0 14 27 1 0 0 0 14 28 1 6 0 0 15 29 1 0 0 0 15 30 1 0 0 0 15 31 1 6 0 0 M END
Conformation search
[Execution by Interface]
Open the Dexmedetomidin.mol file by CONFLEX Interface.
![Interface Dexmedetomidin](images/cduv_dex_interface.png)
Select [CONFLEX] in Calculation menu, and click
in the calculation setting dialog displayed. A detail setting dialog will be displayed.![Basic Settings](images/cduv_dex_interface_basic.png)
Select [Conformation Search] in the pull-down menu of [Calculation Type:] in [General Settings] dialog on the detail setting dialog.
Edit the value of [Search Limit:] to 50.0 in [Conformation Search] dialog on the detail setting dialog.
When the calculation settings are complete, click .
Add [PRECHK] to the dialog displayed, and click
[Execution by command line]
The calculation settings are defined by describing keywords in the Dexmedetomidin.ini file.
Dexmedetomidin.ini file
MMFF94S CONFLEX PRECHK SEL=50.0
- [MMFF94S] means to use MMFF94s force field.
- [CONFLEX] means to perform a conformation search.
- [SEL=50.0] means to set a search limit to 50.0 kcal/mol.
Store the two files of Dexmedetomidin.mol and Dexmedetomidin.ini in an one folder, and execute below command. The calculation will start.
C:\CONFLEX\bin\flex9a_win_x64.exe -par C:\CONFLEX\par Dexmedetomidinenter
The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].
Calculation results
We can get 6 conformers from the conformation search.
No.ID | Conf ID. | Steric E (kcal/mol) | ΔE (kcal/mol) | Distribution (%) |
---|---|---|---|---|
R1 | 2 | 48.8457 | 0 | 47.0162 |
R2 | 5 | 49.1525 | 0.3068 | 28.0111 |
R3 | 3 | 49.2567 | 0.411 | 23.4962 |
R4 | 1 | 51.2498 | 2.4041 | 0.8129 |
R5 | 4 | 51.3723 | 2.5266 | 0.6611 |
R6 | 6 | 54.6699 | 5.8242 | 0.0025 |
CD/UV spectrum calculation
CD/UV spectrum calculations for the conformers are performed. Structure data of R1-R6 conformers are described in Dexmedetomidine.sdf in MDL-MOL file format.
Here, we extract structure data of the R1 conformer from Dexmedetomidine.sdf file and save as Dexmedetomidine_R1.mol.
Structure data of R1 conformer (Dexmedetomidine_R1.mol)
Dexmedetomidine CONFLEX 20120911103D 1 1.00000 48.84570 2 C1 ,E = 48.846, G = 0.585E-07, P = 47.0162, M( 0), IFN =00000001-00000002 31 32 0 0 1 V2000 -2.0874 -0.9516 -1.0953 C 0 0 0 0 0 -3.2087 -0.3537 -1.5970 N 0 0 0 0 0 -3.6187 0.5800 -0.6906 C 0 0 0 0 0 -2.8252 0.6169 0.3538 N 0 0 0 0 0 -1.8462 -0.3288 0.1149 C 0 0 0 0 0 -0.7355 -0.5857 1.0969 C 0 0 0 0 0 0.5101 0.0794 0.5067 C 0 0 0 0 0 0.5314 1.4826 0.3608 C 0 0 0 0 0 1.6413 2.1406 -0.1565 C 0 0 0 0 0 2.7595 1.4107 -0.5382 C 0 0 0 0 0 2.7854 0.0130 -0.4098 C 0 0 0 0 0 1.6575 -0.6664 0.1168 C 0 0 0 0 0 -1.0377 -0.1065 2.5179 C 0 0 0 0 0 1.6676 -2.1687 0.2694 C 0 0 0 0 0 4.0321 -0.7132 -0.8424 C 0 0 0 0 0 -1.5600 -1.7306 -1.6269 H 0 0 0 0 0 -3.6565 -0.5595 -2.4790 H 0 0 0 0 0 -4.4935 1.1972 -0.8447 H 0 0 0 0 0 -0.6109 -1.6715 1.1573 H 0 0 0 0 0 -0.3396 2.0732 0.6439 H 0 0 0 0 0 1.6304 3.2216 -0.2630 H 0 0 0 0 0 3.6185 1.9431 -0.9407 H 0 0 0 0 0 -1.9187 -0.6210 2.9181 H 0 0 0 0 0 -1.2403 0.9691 2.5673 H 0 0 0 0 0 -0.1934 -0.3152 3.1844 H 0 0 0 0 0 1.5390 -2.4397 1.3225 H 0 0 0 0 0 0.8650 -2.6129 -0.3286 H 0 0 0 0 0 2.5987 -2.6334 -0.0623 H 0 0 0 0 0 3.8018 -1.4182 -1.6475 H 0 0 0 0 0 4.7912 -0.0217 -1.2241 H 0 0 0 0 0 4.4752 -1.2463 0.0048 H 0 0 0 0 0 1 2 1 0 0 1 5 2 0 0 1 16 1 6 0 2 3 1 1 0 2 17 1 0 0 3 4 2 0 0 3 18 1 1 0 4 5 1 6 0 5 6 1 0 0 6 7 1 6 0 6 13 1 0 0 6 19 1 1 0 7 8 2 0 0 7 12 1 6 0 8 9 1 6 0 8 20 1 1 0 9 10 2 0 0 9 21 1 0 0 10 11 1 0 0 10 22 1 6 0 11 12 2 0 0 11 15 1 6 0 12 14 1 0 0 13 23 1 1 0 13 24 1 0 0 13 25 1 0 0 14 26 1 1 0 14 27 1 0 0 14 28 1 6 0 15 29 1 0 0 15 30 1 0 0 15 31 1 6 0 M END
[Execution by Interface]
Open Dexmedetomidin_R1.mol file by CONFLEX Interface.
Select [CONFLEX] in Calculation menu, and click
Select [UV/Vis/CD Spectrum] in the pull-down menu of [Calculation Type:] in [General Settings] dialog on the detail setting dialog.
Next, we set parameters for the CD/UV spectrum calculation by [UV/Vis/CD Spectrum] dialog.
Select [Specify...] in [SCF Iterations:] pull-down menu, and input 50. The maximum number of SCF iterations becomes 50.
Set [Occupied Orbital:] and [UnOccupied Orbital:] to 10, respectively. These set the number of occupied orbitals (Nomo) and unoccupied orbitals (Numo) used for one-electron excited CI calculations.
When the calculation settings are complete, click
. The calculation will start.[Execution by command line]
The calculation settings are defined by describing keywords in the Dexmedetomidin_R1.ini file.
Dexmedetomidin_R1.ini file
MMFF94s CDUV SCF_ITER=50 CIS=(10,10)
- [MMFF94S] means to use MMFF94s force field.
- [CDUV] means to perform CD/UV spectrum calculation.
- [SCF_ITER=50] means to set the maximum number of SCF iterations to 50.
- [CIS=(10,10)] means to set the number of occupied orbitals (Nomo) and unoccupied orbitals (Numo) used for one-electron excited CI calculations to 10, respectively.
Store the two files of Dexmedetomidin_R1.mol and Dexmedetomidin_R1.ini in an one folder, and execute below command. The calculation will start.
C:\CONFLEX\bin\flex9a_win_x64.exe -par C:\CONFLEX\par Dexmedetomidin_R1enter
The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].
Calculation results
Results of the CD/UV spectrum calculation are shown at the end of Dexmedetomidin_R1.bso file.
!---------------------------------------------------------------------------------------------------------------------! ! CURVE PLOTTING ! ! SCALING FACTOR: 1.00000 ! !---------------------------------------------------------------------------------------------------------------------! WAVELENGTH(NM) WAVENUMBER(1/CM) UV(STR) UV(VEL) CD(VEL) 1000.000 10000.0 0.00000 0.00000 0.00000 980.392 10200.0 0.00000 0.00000 0.00000 961.538 10400.0 0.00000 0.00000 0.00000 943.396 10600.0 0.00000 0.00000 0.00000 925.926 10800.0 0.00000 0.00000 0.00000 909.091 11000.0 0.00000 0.00000 0.00000 892.857 11200.0 0.00000 0.00000 0.00000 877.193 11400.0 0.00000 0.00000 0.00000 862.069 11600.0 0.00000 0.00000 0.00000 847.458 11800.0 0.00000 0.00000 0.00000 ......
The graph made by this data is shown below. The results of R2-R6 are also shown.