Search Results for "alonso"

Conformations of ephedrine

The Alonso group has once again shown the power of the combination of molecular beam Fourier transform microwave spectroscopy (MB-FTMW) coupled with computations. They examined ephedrine, norephedrine and pseudoephedrine and determined the low energy conformations of each.1 I discuss just the ephedrine case here, but similar results were obtained for the other two compounds.


1

Ephedrine (1) has six potential conformations, differing by the rotation about the C-C bond and the orientation of the methyl group on the nitrogen. They optimized the 6 conformers at MP2/6-311+G(d,p) and corrected the energies for zero-point vibrational energies computed at B3LYP/6-311++G(d,p). The rotational constants and diagonal elements of the 14N quadrupole coupling tensor were computed and obtained by experiment. The comparison of these values (shown in Table 1) made possible the identification of three low energy conformers, labeled as AGa, AGb, and GGa. The structures are shown in Figure 1.

Table 1. Experimental and computeda spectroscopic constants for three conformers of ephedrine.1


 

AGa

AGb

GGa

 

Expt

Comp

Expt

Comp

Expt

Comp

A/MHz

1998.6382

2014

2115.8768

2112

1568.2454

1566

B/MHz

529.5495

533

503.7943

507

592.4485

597

C/MHz

500.1600

505

475.1734

480

572.4160

579

χaa/MHz

2.535

2.63

2.559

2.70

2.448

2.51

χbb/MHz

-2.745

-3.26

-4.621

-4.83

-3.205

-2.90

χcc/MHz

0.210

0.63

2.062

2.14

0.7573

0.39

aComputed at MP2/6-311+G(d,p)


AGa
(0.0)

AGb
(1.35)

GGa
(0.73)

Figure 1. MP2/6-311+G(d,p) computed structures and relative energies (kcal mol-1) of the three conformers of ephedrine.1

The agreement between the experimental and computed spectroscopic values is very good, less than 1.5% for the rotational constants. This excellent agreement makes possible the identification of these three conformers. The experimental population ratio of N(AGa):N(GGa):N(AGb) is 20:4:1, in nice agreement with the computed values. Of structural interest here is the intramolecular O-HN hydrogen bond in each conformer. The authors also suggest a weak hydrogen bond-like interaction between the N-H and the benzene π-system.

References

(1) Alonso, J. L.; Sanz, M. E.; Lopez, J. C.; Cortijo, V., "Conformational Behavior of Norephedrine, Ephedrine, and Pseudoephedrine," J. Am. Chem. Soc., 2009, 131, 4320-4326, DOI: 10.1021/ja807674q.

InChIs

1: InChI=1/C10H15NO/c1-8(11-2)10(12)9-6-4-3-5-7-9/h3-8,10-12H,1-2H3/t8-,10-/m0/s1
InChIKey=KWGRBVOPPLSCSI-WPRPVWTQBH

ephedrine Steven Bachrach 26 May 2009 1 Comment

Cysteine conformers

Alonso and coworkers have developed the technique of laser ablation molecular beam Fourier transform microwave spectroscopy to detect biomolecules. In a recent paper1 they determined the structure of the glycine:one water complex – it is of the neutral configuration. They have now examined the conformations of cysteine2. The presence of the thiol side group adds considerable complexity to the problem due to the many conformations possible.

The experiment detected six conformers. Determining the structures responsible for each set of signals was made possible by comparing the experimental results with those determined by computation. Alonso computed 11 low energy conformations of cysteine at MP2/6-311++G(d,p). Then comparing the computed rotational constants and 14N nuclear quadrupole coupling tensor components with the experiment, they were able to match up all six experimental conformers with computed structures. The experimental and computed constants for the three most abundant structures are listed in Table 1. The geometries of all six conformers are drawn in Figure 1.

Table 1.Experimental and computed spectroscopic constants (MHz) for the three most abundant conformers of cysteine.2

 

IIb

Ia

Ib

 

Expt

MP2

Expt

MP2

Expt

MP2

A

3071.14

3040

4235.63

4221

2889.45

2855

B

1606.54

1623

1187.28

1185

1623.00

1664

C

1331.80

1347

1003.11

1013

1367.83

1386

χaa

-3.12

-3.14

-4.26

-4.67

-0.14

-0.01

χbb

2.44

2.59

2.78

2.86

0.44

0.25

χcc

0.68

0.55

1.49

1.80

-0.30

-0.24

ΔEa

 

0

 

450

 

325

aRelative energy in cm-1 computed at MP4/6-311++G(d,p)// MP2/6-311++G(d,p).

IIb (0.0)

Ia (450)

Ib (325)

IIa (527)

IIIβc (765)

IIIβb (585)

Table 1. Optimized structures of the six observed conformers of cysteine. Relative energies in cm-1 computed at MP4/6-311++G(d,p)//MP2/6-311++G(d,p). (Note – the geometries shown were optimized at PBE1PBE/6-311+G(d,p) since they MP2 structures are not available!)

This study demonstrates the nice complementary manner in which computation and experiment can work together in structure determination.

References


(1) Alonso, J. L.; Cocinero, E. J.; Lesarri, A.; Sanz, M. E.; López, J. C., "The Glycine-Water
Complex," Angew. Chem. Int. Ed. 2006, 45, 3471-3474, DOI: 10.1002/anie.200600342

(2) Sanz, M. E.; Blanco, S.; López, J. C.; Alonso, J. L., "Rotational Probes of Six Conformers of Neutral Cysteine," Angew. Chem. Int. Ed. 2008, DOI: 10.1002/anie.200801337

InChI

Cysteine: InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1
InChIKey: XUJNEKJLAYXESH-REOHCLBHBU

amino acids Steven Bachrach 26 Aug 2008 2 Comments

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