r. d. suenram, justin lindsay neill, jason j. pajski, gordon g. brown, brooks h. pate department of...

R. D. Suenram, Justin Lindsay Neill, Jason J. Pajski, Gordon G. Brown, Brooks H. Pate

Department of Chemistry, University of Virginia, McCormick Rd., P.O. Box 400319, Charlottesville, VA 22904

Michael Tubergen

Department of Chemistry, Kent State University, Kent, Ohio 44242

BROADBAND ROTATIONAL SPECTRA OF THE HYDROXY

BUTYRIC ACID SYSTEM

Gamma Hydroxybutyric Acid

• History of abuse since the 1980’s

• Originally thought to have anabolic effects to increase muscle mass

• In 2000 it became a Federally controlled substance and was designated a Schedule I depressant

• Active field of study by Forensic chemists

Gamma Hydroxybutyric Acid

• GC analysis is difficult because of high polarity and thermal instability.

• Thus conversion to derivatives is necessary– Gamma butyrolactone– Silyl derivatives

Hydroxybutyric Acids

Hbapic1.jpg

B-Hydroxybutyric acid

G-butyrolactoneG-Hydroxybutyric acid

A-Hydroxybutyric acid

11 GHz CP-FTMW Spectrometer

Pulse Monitor

12 GHz Oscilloscope (40 Gs/s)

Free Induction Decay

0.5 – 11.5 GHz

Arbitrary Waveform Generator Chirped Pulse

Frequency Sweep

4 GS/sx8

7.5 - 18.5 GHz

TWTAmplifier

FID acquisition and Fourier transform

9.9 GHz PDRO

2 GHz Bandwidth

Nozzle Sample Feed

18.99 GHz PDRO

AHB Conformer I

6.0 10.0 15.0 19.0

Frequency in GHz

AHB Experimental

AHB Conf I sim

*

*

*

* **

*

AHB Conformer II Spectrum

6.0 10.0 15.0 19.0

Frequency in GHz

AHB Experimental minus Conf I

AHB Conf 2 Sim

AHB Structures

Gauche-1Trans-1

Summary of AHB ResultsConformer gauche- 1 gauche- 2 trans- 1 trans- 2

b3lyp/6- 31+g(d,p)

E (hartree) - 382.96 - 382.956325760 - 382.960174762 - 382.956809576Relative E (1/ cm) 89.06 844.7 0.0 738.6

A (MHz) 3382.68 3538.59 4478.06 4423.90B (MHz) 2219.87 2192.30 1808.60 1743.22C (MHz) 1762.97 1682.79 1403.08 1451.30

mua (D) 0.63 1.15 0.47 0.08mub (D) 2.22 0.79 2.33 0.45muc (D) 0.56 0.04 0.03 1.99

gauche fit trans fit

A (MHz) 3371.53 4507.98B (MHz) 2280.10 1832.72C (MHz) 1821.57 1420.03

mua (D)mub (D) mub > mua ~ muc mub > muamuc (D) not observed

BHB Spectrum

Observed Spectrum

6.5 8.5 10.5 12.5 14.5 16.5 18.5

Frequency (GHz)

BHB simulated Spectrum

Lactone Spectrum (Gonzalez, et. al. J. Mol. Struct. 223 (1990))

Gauche and Trans BHB

Summary of BHB ResultsConformer gauche- 1 gauche- 2 trans- 1 trans- 2

b3lyp/6- 31+g(d,p)

E (hartree) - 382.963420487 - 382.960852574 - 382.965594014 - 382.962147811Relative E (1/ cm) 477.0 1040.6 0.0 756.3

A (MHz) 4507.79 4187.88 5402.30 5135.98B (MHz) 1755.73 1877.46 1611.39 1651.17C (MHz) 1623.95 1649.93 1310.67 1316.23

mua (D) 1.7784 0.0439 1.4010 0.0679mub (D) 2.1337 0.0613 2.1916 0.2826muc (D) 0.0555 0.4373 0.5647 0.2590

Experimental

A (MHz) 5422.4B (MHz) 1620.1C (MHz) 1334.3

mua (D)mub (D) mub > mua > mucmuc (D)

GHB and GBL

Gamma Hydroxybutyric Acid Gamma Butyrolactone

GBL Spectrum

6.0 10.0 15.0 19.0

Frequency in GHz

GBL Experimental

GBL Simulated

A = 7279.8 MHzB = 3585.4 MHzC = 2562.5 MHz

GHB Survey

6.0 10.0 15.0 19.0

Frequency in GHz

GHB Experimental

GBL Spectrum

Subtracted spectrum

Subtracted spectra1. GBL + all 13C isotopomers2. EtAc3. Water dimer

Ab Initio Conformers GHB

E = 0 cm-1 E = 3 cm-1

E = 95 cm-1 E = 160 cm-1

GHB ConformersZPE corrected MP2 optimized constants

MP2 / 6-311++G**E / cm-1 A B C

0 4310 1825 16323 4625 1546 147295 4411 1897 1570

160 6428 1216 1090220 4767 1492 1421326 6355 1190 1099348 4983 1709 1349350 4008 1951 1597411 6426 1206 1146429 5946 1283 1195469 6290 1246 1106475 6201 1271 1180481 3990 1922 1730530 6346 1206 1131554 8286 1053 951605 8220 1046 947

Summary

• Hydroxybutyric acids have internal H-bond

• Hydroxyl H to carbonyl oxygen is preferred

• Theory and experiment agree - generally

• For the GHB system, the lactone is preferred for analysis because of stability and intense spectrum

Acknowledgements

Funding:• NSF Chemistry and MRI Program• University of Virginia