The enediol sp ecies, molecule E, has been proposed as a ta rg e t sp ecies fo r the design of " tra n s itio n s ta t e ” analogue in h ib ito rs of glyoxalase I . I t i s a p lanar molecule in which th e most s ta b le arrangement of the hydroxy groups i s the conform ation in which the hydrogen atoms p o int aw ^ from th e sulphur atom. The energy of th is molecule i s -622.1378 a .u ., which i s comparable to th e -622.1470 a .u . obtained fo r th e s u b stra te analogue, molecule A, and below the en erg ies of th e anionic sp ec ie s C and F (-621.5358 and -621.5513 a .u .
re s p e c tiv e ly ). The optim ised geometry, reported in Table 6-9, i s fo r the 3-21G and 3-21G* b a sis s e ts . Figure 6-9 d e p icts th e optim ised geometry from th e 3 -2 IG* c a lc u la tio n .
An in te re s tin g fe a tu re of th e stru c tu re of th is in term ed iate is the la rg e included angle of th e Cl hydroxyl group, C1-03-H9. This i s
112.7°, whereas th e hydroxyl group angles in the 3-21G b a sis s e t are g enerally around 109°.
The a d d itio n of a proton to th e 03 oxygen of molecule C re s u lts in the form ation of th is enediol sp ec ie s. This i s a favourable re a c tio n lib e ra tin g 0.602 a .u . The e le c tr o s ta tic p o te n tia l map in the plane of molecule C has i t s most negative region in th e neighbourhood of th e
subsequent hydroxyl p ro to n 's p o sitio n .
The change in geometry asso ciated w ith th is re a c tio n dem onstrates the transform ation of a high energy m etastable species in to a s ta b le in term ed iate. There i s no ambiguity about the s tru c tu re : the
carbon-carbon d istan ce i s 1.312 A, a d e fin ite unsaturated bond and the carbon-oxygen bonds are both long, being around 1.4 A, as opposed to
molecule C, where one of these was 1.3 A (Cl-03) and the o th er was 1.43 A (C2-06). The carbon-sulphur distance a lso sh o rten s, as the sulphur p a rtic ip a te s more in the conjugated bonding a t the expense of the oxygen atoms.
The a d d itio n of d -fu n ctio n s to th e sulphur, to convert the 3-&1G b asis s e t re p re se n ta tio n to a 3-21G* one r e s u lts in a shortening of th e C2-S5 bond by 3$ and a shortening of the S5-H7 one by 1,8%. A ll the o th er changes a re of le s s than 1%. This in term ed iate has the g re a te s t to ta l population of d -o rb ita ls of any molecule in the re a c tio n scheme, and has the s h o rte s t C2-S5 bond, w ith the g re a te s t overlap population, of 0.40.
The change in energy of th e in d iv id u al m olecular o rb ita ls can be divided in to two groups as b efo re: th e re are changes brought about by an a d d itio n of s-c h a ra c te r to vario u s o rb ita ls , p a rtic u la rly the f i r s t o r b ita l, which i s predom inantly sulphur Is , due to equal c o n trib u tio n s from th e xx, yy and zz fu n ctio n s; th e re are also changes brought about by an improved d e sc rip tio n of th e IT-bonding in the m olecule. This l a t t e r e ffe c t is found in th e higher occupied o r b ita ls , w ith i t s la rg e s t percentage change in the twenty-second and tw enty-fourth
o r b ita ls . M olecular o r b ita l 24, th e h ig h est occupied m olecular o rb ita l c o n sists of ju s t p^ c o n trib u tio n s of roughly th e same magnitude on Cl, C2, 03, 06 and 85 in the 3-21G wave fu n ctio n . (The z -a x is is
perpendicular to th e plane of th e m olecule). The 3-21G* tw enty-fourth m olecular o rb ita l is s im ila r, except th a t i t also contains a
c o n trib u tio n from the d xz and d -fu n c tio n s. The o r b ita ls which can beyz classed as Tt-bonding s ta te s , w ith p^. c o n trib u tio n s are found to a l l have d„„ and d„ c o n trib u tio n s a lso , xz yz
- 117 -
The carbon-carbon bond of th e o rig in a l enediol sp ecies i s la rg e r by a small amount than th a t of e ith e r th e hydroxy- or the
hy drogen-substituted sp ecies. The o th er bonds a re g en erally comparable to the hydrogen-replaced v alu es, except fo r the p o sitio n in g of th e H8 atom, which is the hydroxyl proton p o intin g towards th e o th er c is hydroxyl group. This i s nearer to the adjacent hydroxyl oxygen, 03, than in th e o th er two cases, w ith a tig h te r C2-06-H8 angle and a la rg e r 06-H8 bond le n g th . The o th er hydroxyl in te rn a l angle, C1-03-H9 i s decidedly la rg e in a l l th re e of th e enediol m olecules, being around
112.5°, The C1-C2-06 angle is a lso tig h te r than fo r th e two
d e riv a tiv e s, pushing the H8 proton even c lo se r to 03, but a l l th re e
2
angles are wider than a normal sp carbon in te rn a l angle, due to th e s tr a in of th e eclip sed conform ation. This compares w ith the much more
3 acute values found fo r the s u b stra te models, which are of course sp carbon c en tres. They are a lso w ider than the corresponding ones fo r the molecule C d e riv a tiv e s, where th e C1-C2-06 angles are about 117°.
A fu rth e r c a lc u la tio n on th e enediol was run using the 3-21G* geometry and th e 6-31G** b a sis s e t. The energy was reduced to -625.2581 a .u ., a red u ctio n of 3.120 a .u . The form of the wave
fu n ctio n was sim ila r to th e 3-21G* one, w ith d^^ and d^^ c o n trib u tio n s to th e -bonding o r b ita ls . The d -fu n ctio n s placed on carbon C2 were almost as w ell populated as those on 85, having 0.092 e le c tro n s as opposed to 0.10 e le c tro n s. The m ajority of th is c o n trib u tio n was to the Pg Tf-bonding o rb ita ls as d^^ and d^^ co n trib u tio n s as noted fo r the o th er m olecules.