Using Maestro and Gaussian 09 in the Qualitative analysis of Endiynes ( enyne-allenes)

Abstract

By Dr. Robert D. Craig,Ph.D.

-8,10,11 trihydroxy- 9- Bicyclo(7:2:2)undec 2- yne,4-ene,6-yne

Students in my group have carried out DFT and various Analytical techniques to study an enyne-allene OR Enediyne- C11H5O4. Mapping the synthesize of C11H5O4 was done with alpha-butanone. The FT-NMR (1H and 13C) and FT-Raman were obtained . The spectra was adequate to analyze and were compared to literature values. The Mulliken, Lowdin, and NBO analysis were also carried out on the enediynes. Students became familiar with DFT analysis , and using the molecule, completed with respect each instrument (UV-VIS, FT-NMR, and FT-IR) using the B-3-YLP/6-311++(2p,3d), MP2, and RHF-STO-3G-basis sets. The calculated HOMO and LUMO values were compared with spectra taken on the Cary Fluorescence spectrophotometer.

Introduction

Ref 1

Enediynes undergo a Bergman cyclization reaction to form the labile 1,4-didehy-drobenzene (p-benzyne) biradical. (1-3) The energetics of this reaction and the related Schreiner–Pascal reaction as well as that of the Myers–Saito and Schmittel reactions of enyne-allenes are discussed on the basis of a variety of quantum chemical and available experimental results. (4-6)The computational investigation of enediynes has been beneficial for both experimentalists and theoreticians because it has led to new synthetic challenges and new computational methodologies. The computer-assisted drug design of new antitumor antibiotics based on the biological activity of natural enediynes in now very popular for the understanding of catalyzed enediyne reactions

Figure one shows Bicyclo(7:2:2)deca 2,4,6-yne-allene-8,10,11 triol -THIS IS J5-NEED 11 PREFIX

Bicyclo[7:2:2] triol molecule 72- C11H5O4 and Molecule 73- C17H11O4

Ref 2

These two molecules are compared as to the stability of the enyne-allene, with the distance of the triple bond.

2. computational Methods

This protocol is intended to provide chemists who discover or make new organic compounds with a valuable tool for validating the structural assignments of those new chemical entities. Experimental 1H and/or 13C NMR spectral data and its proper interpretation for the compound of interest is required as a starting point. The approach involves the following steps: (i) using molecular mechanics calculations (with, e.g., Maestro) to generate a suitable structure; (ii) using density functional theory (DFT) calculations (with, e.g., Gaussian 09) to determine optimal geometry, infrared absorptions and chemical shifts (iii) comparing the computed chemical shifts for two or more candidate structures with experimental data to determine the best fit.

Below in Table xx, is a brief summary of the steps

Table XX:

1. first obtaining computational data for your molecule of interest

1. Draw your biologically significant molecule using Maestro by Schrodinger (i3 processor is fine)

2. produce an "SDF" file

3. open the SDF file in Avogadro-run the Geometry optimization

4. send the Geometry optimized z-matrix to Gaussian 09 (HPCC "Bob")

5 run the FT-IR, Raman, conformation analysis, and FT NMR using the B-3-YLP/6-311++(2p,3d), MP2, and RHF-STO-3G-basis sets

6. You can run PC Gamess/Firefly and "MASK" to get adequate HOMO and LUMO and VPE on an "i3" Core

3. Results and discussion

3.1 geometry

3.2 the vibrational frequencies

3.2.1 C-H

Bicyclo(7:2:2) 2,4,6-yne-allene-4,12,16 triol has aromatic ring structures that can easily be determined due to relation of the C-H and C=C-C ring vibrations. For simplicity, the modes of the vibrations of aromatic compounds are considered as separate C-H and C-C vibrations. The C-H stretching occurs above 3000 cm-and is typically exhibited as a multiplicity of weak to moderate bands, compared with that of aliphatic C-H stretching (25). The C-H stretch vibrations of an aliphatic ring (26) are expected in the region of 3000- 3120 cm-. the calculated values of the target molecule have been found to be 3223.5, 3223.0, 3207.7, 3207.6, 3159.6 and 3187.7 cm- at the using the B-3-YLP/6-311++(2p,3d) level of calculation.

The theorectical computed C-H vibrations by the B-3-YLP/6-311++(2p,3d), are reported here, as this molecule has no been synthesized

The C-H in-plane and out-of-plane bending vibrations generally lie in the range of 1000-1300 cm- and 800-950 cm- (27-29), respectively. In the present case, twelve C-H in-plane bending vibrations of the present compound are identified at the range of 1055.8 -1503.3 cm-. The six C-H out of plane bending vibrations are observed at the range of 750.2-1011.3 cm- and 678.1 cm-. However, as in many complex molecules there are overtones and interactions of these vibrations to weak to be displayed in the spectrum

3.2.2 C-C

Asymmetric, symmetric, bending, C-C modes

3.2.3 C-0-C

Asymmetric, symmetric, bending, wagging C-0-C modes

3.2.4 C=C-DOUBLE

Asymmetric, symmetric

3.2.4 C=C-TRIPLE

Asymmetric, symmetric

3.3 NMR

NMR of yne-allene-C11H5O4

The 1H FT-NMR and 13C FT-NMR were recorded of the two synthesized molecules. Table XXX and Table XXX show the spectra and DFT analysis , as well as prior results (ref xx). Students in my group were able

• To relate spectra to data found in the NIST data base. We also carried out FT-NMR and FT-IR calculations for B-3-YLP/6-311++(2p,3d), MP2, and RHF-STO-3G-basis sets via the HPCC supercomputer which hosts G09. Gaussview 5 was used to adjust the appropriate z-matrices, and Maestro (Schrodinger Inc.) was available on a “i3” core Pentium to produce accurate

depictions of the molecule.-Rebecca!! OH

– Aliphatic d 0.5-4.0 ppm (depend on Concentration)

– Intramolecular hydrogen bonding deshield OH and render it less sensitive to concentration

• Usually OH exchange rapidly (no coupling with neighbors

• In DMSO or Acetone, the exchange rate is slower => there is coupling with neighbors

• Phenols : d 7.5-4.0 ppmIntramolecular bond 12-10 ppm

• Carboxylic Acids : Exist as Dimers 13.2-10 ppm

Figure xxx: The 1H FT-NMR and 13 FT-NMR of molecule 72 and Molecule 73 taken on

The 1H FT-NMR and 13 FT-NMR of yne-allene-C11H5O4 molecule 72 and Molecule 73 taken on

Example 1H NMR spectrum (1-dimensional) of a mixture of menthol enantiomers plotted as signal intensity (vertical axis) vs. chemical shift (in ppm on the horizontal axis). Signals from spectrum have been assigned hydrogen atom groups (a through j) from the structure shown at upper left

The 1H FT-NMR and 13C FT-NMR of yne-allene-C11H5O4 molecule 72 and Molecule 73 taken on

Table 3: proton FT-NMR of yne-allene-C11H5O4 molecule 72

Exp B3LYP MP2 RHFH1H2H3H4H5

Table 4: carbon 13C FT-NMR of yne-allene-

C11H5O4 molecule 72Exp B3LYP MP2 RHF

C1C2C3C4C5C6C7C8C9C10C11

UV-Vis of yne-allene-C11H5O4 Molecule 72

Below are the pictures of the Homo and lumo of Molecule 72 (figure xx).

In table xx, we give the data for the energies of the homo and lumo for yne-allene-C11H5O4 Molecule 72 and molecule 73. The Homo and lumo of biologically interesting molecules are the frontier orbitals. They are the states in which the molecules resides, and thus the states needed to examined the most

Figure xxx: Homo- of yne-allene-C11H5O4 Molecule 72

Figure xxx: Lumo of yne-allene-C11H5O4 Molecule 73

Table xx: energies of the homo and lumo for yne-allene-C11H5O4 Molecule 72

Some of the calculated energy values of yne-allene-C11H5O4 molecule 72 in its ground state with tripletSymmetry at the RHF-STO-3G methods

RHF-STO-3GLowest MO Eigen value (a.u.) -20.3173Highest MO Eigen value (a.u.) 1.4306HOMO (a.u.) -0.0173LUMO (a.u.) 0.1506HOMO-LUMO gap, delta E (a.u.) 0.1679

The Highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital are very important parameters for quantum chemistry. We can determine the way the molecule interacts with other species ; hence they are called frontier orbitals. HOMO, which can be thought the outermost orbital containing electrons, tend to give these electrons such as an electron donor. On the otherhand, LUMO can be thought the innermost orbital containing free places to accept electrons. (35) . Owing to the interaction between HOMo and LUMO orbital of a structure transition state transition state pi-pi* type observed with regard to molecular orbital theory (36) . Therefore,while the energy of the HOMO is directly related to the ionization potential, LUMO energy is directly related to the electron affinity. Energy difference between HOMO and LUMO orbital is called as energy gap that is an important stability for structures (37) . A large HOMO –LUMO gap implies high kinetic stability and low chemical reactivity, because it is energetically unfavorable to add electrons to a high-lying LUMO, and to extract electrons from low-lying HOMO (38) . The magnititude of the HOMO-LUMO energy separation could indicate the reactivity pattern for the molecule(39) . In addition, 3D plots of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are shown in figure XXX and figure XXX

NBO ANALSIS OF yne-allene-C11H5O4 MOLECULE 72

Mulliken atomic charges:#UHF/6-311G** Units=AU Field=F(2)10 Scf=Tight

1 Atom Mulliken

Lowdin

1 C 0.106580 1 C 0.13 0.09 2 O -0.464684 2 O -0.23 -0.14 3 C 0.237856 3 C 0.1 0.05 4 C 0.929137 4 C 0.11 0.08 5 C -0.946121 5 C -0.04 -0.04 6 C -0.119745 6 C -0.04 -0.04 7 C 0.517174 7 C -0.09 -0.1 8 C 0.091799 8 C -0.02 -0.02 9 C -1.048213 9 C -0.09 -0.06 10 H -0.304253 10 H 0.1 0.06 11 C 0.528524 11 C 0.07 0.08

12 C 1.454406 12 C 0.06 0.07 13 H -0.511770 13 H 0.08 0.04 14 O -0.314870 14 O -0.29 -0.21 15 H -0.215294 15 H 0.2 0.14 16 C 1.937672 16 C 0.06 0.07 17 H -0.717993 17 H 0.07 0.03 18 O -0.366829 18 O -0.29 -0.21 19 H -0.408051 19 H 0.2 0.14 20 O -0.209599 20 O -0.29 -0.19 21 H -0.175723 21 H 0.22 0.16

Mulliken atomic charges:

#UHF/6-311G** Units=AU Field=F(2)10 Scf=Tight

1

1 C 0.106580

2 O -0.464684

3 C 0.237856

4 C 0.929137

5 C -0.946121

6 C -0.119745

7 C 0.517174

8 C 0.091799

9 C -1.048213

11 C 0.528524

12 C 1.454406

13 H -0.511770

14 O -0.314870

15 H -0.215294

16 C 1.937672

17 H -0.717993

18 O -0.366829

19 H -0.408051

20 O -0.209599

21 H -0.175723

CALCULATED BOND DISTANCES AND EXPERIEMENTAL X-RAY DATA

UV -VIS

Next is the spectrum taken by our group of Bicyclo(7:2:2) 2,4,6-yne-allene-4,12,16 triol on the Cary Flourescence spectrophometer. Figure xxx is shown first. It shows pi to pi* transitions of the 1,9 diene,3 –yne-doca-aryne ring

Figure xxx: Flourescence of molecule Bicyclo(7:2:2) 2,4,6-yne-allene-9,10,13 triol

taken on the Cary Flourescence spectrophometer

FT-IR of Molecule 72

FT-IR spectroscopy of Bicyclo(7:2:2) 2,4,6-yne-allene-9,10,13 triol

molecule 72 was performed on fourier-tranformed infrared spectrophotometer (Bruker VECTOR 22) equipped with a detector (DTGS) which has a resolution of 4 cm-1 . The pellets of the samples (10 mg) an potassium bromide (200 mg) were prepared by compressing the powders at 5 bars for 5 minutes on KBr press and the spectra were scanned on the wave number range of 4000-850 cm-1 .

The vibrational frequencies of molecule 72 and molecule 73 were calculated on “Bob” of the HPCC at the College of Staten island. To assign the frequencies, the gaussview program was used.

Before a Z-matrix is generated to obtain any of the vibrational frequencies, electronic transitions or nuclear magnetic resonances of molecule 72 and molecule 73, we sent the “pds” file to AVOGADRO. This piece of software automatically does a geometry opimitization of the ground state of the molecules.

The molecular structure and vibrations frequecies in figure xxx, are optimized by HF, beck 3-Lee-Yang-Parr (B3LYP) and Moller-Plesset pertubation theory (MP2) functions using 6-31+G(d,p) basis set.

6-31+G(d,p)

basis Frequencies

Approximate Selected Freq.

(cm-1) type of mode Value Rating

46.443

90.2773

103.9909

155.9329

178.4513

202.9863

336.987

352.3439

376.9907

392.476

418.0662 Ring deform 410 C456.3225

471.4012

492.176

506.6196

595.0455 Ring deform 606 C633.2742

680.9222 CH bend 673 B

695.1723 Ring deform 703 E

765.1576

795.5685

806.3163

849.807

917.6558

939.3541 Ring str 992 C

1060.9691 Ring str Ring deform 1010 C

1105.0525 Ring deform 1010 C

1146.4633 CH bend 1150 C

1169.9673 CH bend 1150 C

1235.9834 CH out-of-plane1281.3576 CH out-of-plane1304.2065 Ring str 1310 C

1330.3879 CH bend 1326 E

1368.217

1422.439

1430.197

1436.8364 Ring str + deform 1486 B1489.6613

1511.8523

1539.0105

1575.7404

1592.5735

1727.6637

1779.8043

3253.3104

3271.6279

3351.2596

3953.3827

3996.3253

4046.6678

Figure xxx: FT-IR spectra of molecule 72 taken on the (Bruker VECTOR 22) spectrophotometer

Table 3: FT-IR of molecule 72

Sym. NoApproximat

eSelected Freq. Infrared

Exp B3LYPSpecies type of mode Value Rating Value Phase

a1g 1 CH str 3062 C iaa1g 2 Ring str 992 C iaa2g 3 CH bend 1326 E iaa2u 4 CH bend 673 B 673 S gas

b1u 5 CH str 3068 C 3067.57 VW

sln.

b1u 6Ring deform

1010 C 1010 W sln.

b2g 7 CH bend 995 E ia

b2g 8Ring deform

703 E ia

b2u 9 Ring str 1310 C 1310 W liq.

b2u 10 CH bend 1150 C 1150 W liq.

e1g 11 CH bend 849 C iae1u 12 CH str 3063 E 3080 S liq.

e1u 12 CH str 3063 E 3030 S liq.

e1u 13Ring str + deform

1486 B 1486 S gas

e1u 14 CH bend 1038 B 1038 S gas

e2g 15 CH str 3047 C iae2g 16 Ring str 1596 E iae2g 16 Ring str 1596 E iae2g 17 CH bend 1178 C ia

e2g 18Ring deform

606 C ia

e2u 19 CH bend 975 C 975 W liq.

e2u 20Ring deform

410 C 417.7 S sln.

e2u 20Ring deform

410 C 403.0 S sln.

References

Ref 1

Elfi Kraka, Dieter Cremer, ”Enediynes, enyne‐allenes, their reactions, and beyond”, Corros. Sci. 50 (2013) 1174

Published Online: Oct 08 2013DOI: 10.1002/wcms.1174

How to cite this article

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Masahiro Hirama, Kimio Akiyama, Parthasarathi Das, Takashi Mita, Martin J Lear, Kyo-Ichiro Iida, Itaru Sato, Fumihiko Yoshimura, Toyonobu Usuki, Shozo Tero-Kubota

DIRECT OBSERVATION OF ESR SPECTRA OF BICYCLIC NINE-MEMBERED ENEDIYNES AT AMBIENT TEMPERATURE

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(38) B. Chattophadhyay, S. Basu, P. Chakraborty, S.K. Choudhury, A.K. Mukherjee, M. Mukherjee, J.Mol. Structu 932 (2009) 90.

7. Willoughby, P. H., Jansma, M. J. & Hoye, T. R A guide to small-molecule structure

assignment through computation of (1H and 13C) NMR chemical shifts. Nature Protocols 9, 643–

660 (2014)

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