Molecular Modeling of Acyclic Carbohydrate Derivatives - American

Chapter 8

Molecular Modeling of Acyclic Carbohydrate Derivatives N,N'-Dimethyland N,N'-Dihexylxylaramide Downloaded by PENNSYLVANIA STATE UNIV on February 16, 2013 | http://pubs.acs.org Publication Date: July 6, 1990 | doi: 10.1021/bk-1990-0430.ch008

Model Compounds for Synthetic Poly(hexamethylenexylaramide) 1

1

1

1

2

L. Chen , B.Haraden ,R. W. Kane , D. E. Kiely , and R. S. Rowland 1

2

Department of Chemistry and Department of Biochemistry, University of Alabama, Birmingham, AL 35294

Some results on the molecular modeling of Ν,Ν'-dimethylxylaramide ( 1 ) and N,N'-dihexylxylaramide (2) using MacroModel V.2 are presented. Nine minimized conformers were considered and their populations calculated. Average J -J couplings are then calculated and those values compared to experimental coupling values. A good fit was obtained for each compound after adjusting the van der Waals cutoff radii option to 3 Å. Two sickle conformations and an extended zig-zag conformation were calculated as the dominant conformers for the xylaramides 1 and 2. A case is made for the similarity in conformational populations of xylitol and xylaramides, both unprotected and as hydroxyl protected forms. 2,3

3,4

We have recently developed a synthetic procedure f o r the prepar ation of polyhydroxypolyamides (hydroxylated nylons) of general structure I (1-2). While our synthetic method has some unique

-[6-(CHOH) - x

(CH ) -N]2

y

n

features, syntheses of examples of t h i s class of polymer have been previously reported, f i r s t by Ogata and co-workers (3) and more recently by Hoagland (4). In order to study the conformational c h a r a c t e r i s t i c s of the a c y c l i c carbohydrate monomer components of such polymers, we have recorded the H NMR spectra of the polymers and begun to compare experimental coupling constants with those generated using molecular modeling techniques. Results as applied to J^JV'-dimethylxylaramide ( 1 ) and A^tf'-dihexylxylaramide (2), models f o r poly(hexamethylenexylaramide) ( 3 ) , are presented. 0097-6156/90/0430-0141$06.00/0 © 1990 American Chemical Society

In Computer Modeling of Carbohydrate Molecules; French, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1990.

142

COMPUTER MODELING OF CARBOHYDRATE MOLECULES

RESULTS AND DISCUSSION The H NMR spectra (300 MHz) of the model diamides 1 and 2, and the polyamide 3, were recorded i n t r i f l u r o a c e t i c acid-d (TFA-d). Since the xylaramide component of 1-3 i s symmetrical, one observes a single average coupling f o r -H and H^-H - Experimental values f o r J = J are: f o r 1, 3.45 Hz; f o r 2, 3.32 Hz, and f o r 3, 3.26 H z ^ (See Table I.) Figure 1 shows the relevant portion of the H NMR spectra from model compound 2 and the polymer 3. Since the v i c i n a l proton coupling values f o r 1-3 are a l l very s i m i l a r , i t was concluded that 1 and 2 should be good conformational models f o r the carbohydrate component of the polyamide 3. We then turned to molecular modeling to t r y to determine the populations of the p r i n c i p a l (low energy) conformations of 1 and 2 that give r i s e to the observed average coupling values. Measured v i c i n a l proton coupling values have been used extensively to assign approximate dihedral angles and preferred conformations f o r a c y c l i c carbohydrates (5), commonly as t h e i r per-O-acetyl derivatives (6,7). Based upon a number of such studies i t has been concluded that conformations of a c y c l i c carbohydrates i n solution with 1,3-parallel interactions between OH or OR groups are unfavorable. To r e l i e v e these unfavorable interactions a c y c l i c carbohydrates t y p i c a l l y undergo 120° rota tions about appropriate C-C bonds to form "bent" or " s i c k l e " conformations. Of p a r t i c u l a r relevance to the subject of t h i s paper, are the studies by Angyal et a l . on the conformational analysis of x y l i t o l pentaacetate (5, reference 8) and a recent jeport by Franks and co-workers describing a high f i e l d (620 MHz) H NMR study on x y l i t o l i t s e l f (4, reference 9). X y l i t o l and i t s pentaacetate, l i k e the xylaramides of our study, are symmetrical a c y c l i c xylose derivatives with a single average coupling from ~ 3 and H--H-. V i c i n a l proton coupling constants ( J = J ) for compounds 1-5 are given i n Table I. I t i s of interest to note 1

H

Downloaded by PENNSYLVANIA STATE UNIV on February 16, 2013 | http://pubs.acs.org Publication Date: July 6, 1990 | doi: 10.1021/bk-1990-0430.ch008

3

H

4

H

2

23

TABLE I .

J

2

3

COUPLING

Constants f o r Compounds

J

2,3

HZ

< >

3.45°

c

3.32

34

3.26°

1-5

4.49" 3. 65. 3. 40

C

5.2

C

a. b. c. d. e.

T r i f l u r o a c e t i c acid-d as solvent D 0 as solvent, reference 9 Pyridine-d5 as solvent, reference 9 Acetone-d6 as solvent, reference 9 CDC1 as solvent, reference 8 2

that the backbone proton signals from x y l i t o l pentaacetate are adequately separated at 250 MHz (8), but those of x y l i t o l are poorly separated at the same spectrometer frequency.


Molecular Modeling of Acyclic Carbohydrate Derivatives


CHEN ET AL.

2 R= H 2a R = TMS

4 R=H 5 R = Ac λ

FIGURE 1. Ε NMR SPECTRA (3.3 - 5.1 ppm) of Poly(hexamethylenenexYlaramide) (3) and N,N -Dihexylxylaramide (2) i n TFA. Signals at 4.99 and 4.88 are from the xylaramide moiety (H-2,4 and H-3 r e s p e c t i v e l y ) ; the signal at 3.51 ppm i s from ND-CH . %


143

144

COMPUTER MODELING OF CARBOHYDRATE MOLECULES

Angyal and co-workers (8) concluded that the conformational d i s t r i b u t i o n of x y l i t o l pentaacetate i n CDCl^ i s between two s i c k l e conformations with the extended zig-zag conformation being unimportant. The ^~ 3 4 9 value of 5.2 Hz i s from a large coupling from ântipârallel H ~H (or H ~H ) and a small coupling from ~ 3 ^ 3~ 4^' P ' Franks et a l . (9) obtained couplings f o r " 3 3~ 4 Y i three d i f erent solvents with a l l values being lower than those recorded f o r x y l i t o l pentaacetate (Table I ) . The 3^ values f o r x y l i t o l i n pyridine-d5 and acetone-d6 (3.65 and 3.40 Hz respectively) are close i n value to those we observed f o r compounds 1-3 (3.48-3.26 Hz range) suggesting average conformational s i m i l a r i t y of x y l i t o l and xylaramides around the C -C^-C^ bonds. These smaller coupling values also suggest a lower " s i c k l e " conformation contribution from x y l i t o l and the xylaramides than i s observed with x y l i t o l pentaacetate. In an attempt to test t h i s l a t t e r hypothesis f o r the xylar amides 1-3, we c a r r i e d out a molecular modeling study using the MM2 based MacroModel V 2.0 program (11-12). This study was done using an Evans and Sutherland Terminal PS 350 and a Vax 11-750 computer. As stated i n reference 11, "The MacroModel MM2 f i e l d d i f f e r s from the standard f i e l d i n that i t uses the point charge e l e c t r o s t a t i c model with p a r t i a l charges derived from the MM2 bond dipoles whereas the standard MM2 e l e c t o s t a t i c treatment uses a dipole-dipole model." Information concerning the MacroModel molecular modeling program i s available from W. C. S t i l l , Department of Chemistry, Columbia University, New York, New York 10027. For a l l of the calculations we used the same protocol i n choosing conformations f o r minimization, but obtained d i f f e r e n t r e s u l t s by changing program parameters available on the program menu. J

a v e r a

e

3

H

H

o rH

H

B

v

4

c o m

2

3

a r i s o n

2

H

H

a

n

d H

H

o

f

x

1

t o 1

i

n


2

Protocol

Used

For Selection

of

Conformations

to

Be

Minimized

1) The H-N and C=0 of the amide (H-N-C=0) groups were placed i n the more stable anti r e l a t i o n s h i p (13). 2) The f u l l y extended zig-zag conformation ( a l k y l groups and xylo component) was minimized and minimizations were then done on f i v e additional conformers generated by 60° increment rotations around the C^-C^ bond of the xylo moiety. A second set of conformers was produced by rotation i n 60° increments around the C ~C^ bond on the lowest energy conformer i n the f i r s t set. This process gave a single, minimized, f u l l y extended, zig-zag conformer simply designated as Extended (Figure

2).

3) Successive rotations of 120° i n a clockwise or counter clockwise d i r e c t i o n around the " 3 ^ 3 ~ 4 ^ ^ were c a r r i e d out on the Extended conformation from above. Each of these conformers was minimized further by 60° rotations around the C^-^ * 4~ 5 ^ This process gave an additional eight conformers (Figure 2). C

C

a n

Molecular Modeling of Acyclic Carbohydrate Derivatives - American

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