The fin a l product of the model re a c tio n scheme i s molecule H. This
3 2
has an sp carbon a t Cl and an sp one a t 02 - th e opposite to th e o rig in a l molecule A. Unlike m olecule A, i t i s a symmetrical m olecule, of Os symmetry. I t has been optim ised fu lly a t both the 3-21G and 3-21G* le v e ls , the r e s u lts of th a t o p tim isatio n s are presented in Table 6-10 and the 3-21G* geometry is shown in Figure 6-10.
The carbon-carbon bond length i s la rg e r than th a t of molecule A, being 1.521 A, compared to 1.509 A. The carbonyl carbon-oxygen bond len g th , 02-06, is s lig h tly la rg e r than the o rig in a l carbonyl len g th fo r 01-03 and th e carbon-oxygen d istan ce fo r the hydroxy group is also la rg e r than fo r m olecule A. The carbon-sulphur i s almost as sh o rt as the enediol carbon-sulphur d ista n ce , being 1.766 A and the to ta l d -fu n ctio n c o n trib u tio n to th e wave function is also second only to molecule E, being 0.140 e le c tro n s in to ta l.
Molecule H i s e n e rg e tic a lly more sta b le than the isom eric
molecules A and E, in fa c t, i t i s the most s ta b le molecule in the model scheme, the to ta l energy of the sp ecies being -622.1608 a .u .
The main d ifferen c e in the geom etries of the 3-21G optim ised and th e 3-21G* optim ised r e s u lts i s again th e C2-S5 bond len g th , which is reduced by 4.4%, and th e S5-H8 d ista n ce which i s reduced by 1.9%. The sulphur atom and the carbonyl oxygen combine to p u ll e le c tro n s away from C2, making i t q u ite p o s itiv e , w ith a M ulliken atomic charge of 0.30. In fa c t, th is i s th e most p o sitiv e C2 carbon in the whole
scheme, ju s t as 02 i s th e most negative fo r molecule A. This re v e rsa l of charge on carbon when comparing th e s u b stra te and product models i s
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also n o ticeab le on Cl, where a charge of 0.31 becomes one of -0.14 as
2 3
Cl changes from an sp carbon to an sp one. This i s an enhancement of the e ffe c t observed fo r th e conversion of the is a n e rs C to F, in which th e re i s a sim ila r re v e rsa l of charge a t these c en tres.
The h ig h est occupied m olecular o rb ita l shows a c o n trib u tio n from th e d - and d „„-fu n ctio n s, as do a l l the o th er o rb ita ls w ith xz yz
c o n trib u tio n s from th e p ^-fu n ctio n s. The g re a te s t change in energy, upon adding the d -fu n ctio n s to th e sulphur atom is a 1.5% redu ctio n in the energy of m olecular o rb ita l 23, the second h ig h est occupied
o r b ita l. This has a c o n trib u tio n from the d ^ -fu n c tio n , but i t s major c o n trib u tio n s are p^ c o e ffic ie n ts on 85 and 06. M olecular o r b ita l 22 in creases in energy by 1.4% and has co n trib u tio n s from sulphur d^^- and dyg- as w ell as from th e p^-fu nctio n s on the o th er atoms.
The to ta l population of th e d -fu n ctio n s i s 0.140 fo r molecule H, second only to molecule E, the enediol sp ec ie s. Both th ese m olecules a re n e u tra l and have a p lan ar S-C-0 region in th e ir s tru c tu re . The
2
in te ra c tio n between th e sp carbon and the sulphur d -o rb ita ls is strong in th ese m olecules; th e C2-S5 overlap population i s .large fo r th ese species too.
The e ffe c t of th e a d d itio n of d -o rb ita ls i s a lso apparent in a comparison of th e M ulliken to ta l atomic charges. The charges on Cl, 03, H4 and HT are about th e same fo r both 3-21G and 3-21G* wave fu n ctio n s, but the -charge on 02 and 85 a lte r s : th a t on 02 in creases from 0.20 to 0.30 and th e charge on 85 decreases from 0.10 to 0.02, as more e le c tro n s occupy th e sulphur o rb ita ls a t the expense of the
carbon. The 02-85 overlap population in creases from 0.31 to 0.38 and the population on 02 i s reduced (5.44 -> 5.24) and th a t on 85 is increased (15.61 -> 15.75).
I f th e th io l group i s replaced by a hydroxy group or a hydrogen atom, the re s u ltin g change in geometry and e le c tro n d is trib u tio n i s evident in th a t region of th e molecule only: th e hydroxy sid e of the molecule is u n affected . The C1-C2 carbon-carbon bond shrinks
considerably when th e sulphur is replaced b an oxygen atom. Likewise, the to ta l atom ic charge p a tte rn i s only changed in th e region of C2,
(ignoring th e X5 sid e group). C2 has a charge of 0.30 fo r th e th io l and hydrogen d e riv a tiv e s, but a charge of 0.80 fo r th e hydroxy
sp ecies. The overlap population on 02 i s a lso decreased in the hydroxy d e riv a tiv e , from 5.07 to 4.54.
The use of the 6-31G** b a sis s e t a t th e 3-21G* optim ised geometry re s u lts in a red u ctio n of the energy by 3,248 a .u ., to .,-625.2948 a .u . The la rg e s t population of d -fu n ctio n s are again found on 02 and 85, being 0.11 and 0.10 e le c tro n s re sp e c tiv e ly .
6.8 £le.tttr.o.8.ta,t.lc....Rotential cslouletl cns
The m olecular e le c tr o s ta tic p o te n tia l maps in th e plane of the O-C-C-0 framework were c a lc u la te d fo r th e optim ised gecm etries of the model compounds, using a v ersio n of th e DENPOT program [139],
incorporated in to th e GAÜ88IAN 80 program [138]. The van der Waals surface e le c tr o s ta tic p o te n tia ls were also c a lc u la te d , using another v ersion of GAUSSIAN 80 [143]. These were p lo tte d using th e colour p lo ttin g program described in Chapter 5. The re s u ltin g p ic tu re s are shown in Figures 6-11 to 6-18.
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The main d iag n o stic fe a tu re of th e planar diagrams is th e p o sitio n of the negative p o te n tia l w e lls, which can be equated to the oxygen and sulphur lone p a irs . At th e s t a r t of the model enzyme re a ctio n ,
molecule A has a la rg e w ell around th e 03 carbonyl oxygen and a sm aller one on th e excluded sid e of C2-06-H8 a t a d istan ce of about 4.8 A,
Upon removal of th e H7 proton, to form the anionic sp ec ie s, molecule C, th e re is an extensive change in the s tru c tu re of the MEP. As i s the case fo r most anionic sp e c ie s, th e surrounding e le c tr o s ta tic p o te n tia l i s negative in alm ost every d ire c tio n , as the o v e ra ll negative charge w ill a t tr a c t a p o s itiv e p o in t charge from any sid e. However, the
minima are again a sso ciated stro n g ly w ith the two oxygens, as one would expect and are about th e same d istan ce a p a rt, a t 4,7 A. The shape of the w ells has changed, though. Molecule A has a su b sta n tia l ridge of p o sitiv e p o te n tia l between the two oxygens, due to th e H9 hydrogen, but th is is very much reduced in molecule C so th a t the p o sitiv e p o te n tia l does not protrude even as f a r as th e van der Waals surface of th is atom.
I f we now consider molecule E, the enediol sp ecies, we fin d a d iffe re n t p a tte rn again; the minima asso ciated w ith the oxygens have shrunk to a q u ite sm all siz e compared to molecule A. Not only has the ad d itio n of a proton to th e carbonyl o:^gen reduced the siz e of th is atom 's negative region, but also th e hydroxy oxygen, 06, has a reduced n e j^ tiv e reg io n . This i s because th e atom H7 i s now in the plane of the m olecule, pinching th e negative region between i t s re p u lsiv e, p o sitiv e c o n trib u tio n to the MEP and th a t of the H8 hydrogen. The d istan ce between th e negative regions fo r th is sp ecies is about 3-4 A, as the p o sitio n of th e minimum asso ciated w ith 03 has changed because of i t s atten d an t hydrogen atom, H9.
Molecule F, being another anionic species does not have any
appreciable p o s itiv e p o te n tia l o u tsid e the van der Waals su rface in th e plane of the m olecule. Again, th e deepest p a rt of the negative areas are about 4.5 A a p art and th e shape of the map i s rem iniscent of th a t of the isom eric molecule C, except th a t th e regions asso ciated w ith th e oxygens are rev ersed .
The fin a l sp ecies, m olecule H, has the la rg e s t negative region of any n e u tra l sp e c ie s, asso ciated w ith i t s hydroxyl oxygen and a more compact oarboi^l region of a sim ila r size to th e o rig in a l hydroxy oxygen region of m olecule A. The negative w ells are again about 4.3 A a p a rt.
The e le c tr o s ta tic p o te n tia l on th e van der Waals Connolly surface has also been calcu lated fo r c e rta in members of the re a c tio n scheme.
The c a lc u la tio n was r e s tr ic te d to th e n e u tra l members of the scheme, as th e anionic sp ecies cannot be d ire c tly compared to th e n e u tra l
in h ib ito r m olecules. The r e s u lts a re shown in Photographs 1 to 4, The van der Waals su rface e le c tr o s ta tic p o te n tia l p lo ts have negative regions asso ciated w ith th e oxygen and sulphur atoms, as one would expect. The enediol sp ec ie s, molecule E, also has a negative
region between the two carbon atoms, whereas th e su b stra te and product analogues, m olecules A and H, have a p o sitiv e p o te n tia l in th is a re a . Thus th e conversion of th e bond between the carbons of the su b stra te to an u n satu rated , rig id bond i s accompanied by a complete change in the p o te n tia l of th is a re a. A " tra n s itio n s ta t e ” in h ib ito r of th is enzyme might be expected to have a sim ila r p o te n tia l in th is region, or a t le a s t i t should not have th e p o sitiv e reg io ns. This w ill be discussed in the next chapter.
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