J. Am. Chem. Soc. 1998, 120, 12127-12128
12127
Coupling of Catalyses by Carbonyl Clusters and
Dehydrogenases: Reduction of Pyruvate to L-Lactate
by Dihydrogen
Scheme 1. Proposed Catalytic Cycles for the Reduction
Mechanisma
,
†
‡
‡
Sumit Bhaduri,* Pradeep Mathur, Pramatha Payra, and
Krishna Sharma§
Research & Consultancy Directorate
Associated Cement Company, Thane 400 604, India
Chemistry Department, Indian Institute of Technology
Bombay 400 076, India
Jaysynth Dye Chem Limited, P.O. Rasayani
Patalganga 410 220, India
ReceiVed July 31, 1998
The unique catalytic potentials of carbonyl clusters have been
1
the subject matter of much current research. Here we describe
+
the use of a platinum cluster for the catalytic reduction of NAD
to NADH by dihydrogen. By using the enzyme L-lactate dehy-
drogenase (L-LDH) the scope of this reaction has been extended
+
to include reduction of pyruvate to L-lactate. Since both NAD
and L-LDH are soluble only in water, and the carbonyl cluster is
soluble only in organic solvents, a biphasic system consisting of
water and dichloromethane has been used. The cluster catalyzes
a
For clarity “CO” groups of the platinum clusters are not shown. The
dashed vertical line is a schematic representation of the phase boundary
+
the reduction of a redox active dye, Safranine O (Saf , 3,7-dia-
2 2
between the CH Cl and water phases.
mino-2,8-dimethyl-5-phenylphenazinium), by dihydrogen in the
+
organic phase. The oxidized (Saf ) and the reduced (SafH) dye
An alternative strategy based on the concept of a “shuttle carr-
ier” was therefore used. Such carriers play a vital role in the tran-
sport of electrons, protons, cofactors, etc. across the biological
membranes. It was felt that redox active dyes may function as
suitable shuttle carriers. Dyes such as methyl viologen (MV ),
methylene blue (MB ), Saf , and dichloroindophenol sodium salt
(Ind ) have been used as artificial electron acceptors in biological
systems. The one-electron MV /MV couple has in fact been
used to effect the reductions of NAD . We first established that
shuttles across the phase boundary and facilitates the transfer of
two electrons and one proton.
The ability of [Bu
with two protons according to reaction i is well established.
4 2
N] [Pt12(CO)24] (1) to equilibrate dihydrogen
5
2,3
2
+
+
+
+
+
-
3
[Bu N] [Pt (CO) ] + H h 6[Bu N] + 2H +
4
2
12
24
2
4
6
2+
+•
2-
4
[Pt (CO) ] (i)
9 18
+ 7
in a single solvent such as DMF or in a biphasic system reaction
iii does take place, and by combining (i) and (iii) a catalytic cycle
for dihydrogen driven reduction of Dyeox (Scheme 1a) could be
set up.
As the aim has been to develop a catalytic system for dihy-
drogen driven reductions of cofactors such as NAD and FMN,
the feasibility of reaction ii has been evaluated.
+
2-
+
2-
2-
+
2-
4
[Pt (CO) ] + 2H + A h 3[Pt (CO) ]
+
4[Pt (CO) ] + Dye + 2H h 3[Pt (CO) ]
9
18
ox
12
24
+
9
18
12
24
+
+
(
2 - x)H + AH (ii)
Dyered + nH (iii)
x
+
+
+
2+
-
(
2
Dyeox ) Saf , MB , 2MV , Ind ; Dyered ) SafH, MBH,
A ) NAD , x ) 1; A ) FMN, x ) 2
+
•
-
MV , IndH
2
; n ) 1, 1, 2, 0, respectively).
Mixing of DMF solutions of 2 and Dyeox leads to formation
of 3 and bleaching of Dyeox, or in the case of MV , development
of the deep purple color of MV . In all cases conversion of 2 to
is seen by IR, and for MV , formation of the radical cation is
evident from an isotropic ESR signal at g ) 2.03. When dihydro-
gen is passed through a biphasic system, consisting of equal
2 2
volumes of a solution of 1 in CH Cl and a solution of Dyeox in
water (Dyeox to 1 molar ratio g 10:1), the water layer is gradually
bleached. Spectral recording of the dichloromethane layer at the
end of the reaction shows only 2 to be present. Formation of acid
(CO)18]2 (2) directly with
-
The main problem of reacting [Pt
the cofactors is the solubility properties of the cofactors and the
platinum cluster. In predominantly aqueous systems (water
95%), with small amounts of a miscible organic component
9
2+
+
•
2
+
3
>
such as DMF or DMSO, the cofactors have some solubility but
+
the sodium or [Bu
system consisting of water and CH
effected. We also evaluated the catalytic potential of [Pt12(CO)24
3), anchored onto biocompatible QAE-sephadex for the reduction
4
N] salt of 2 is unstable. Also, in a biphasic
2
2
Cl , reaction ii could not be
2-
]
(
+
4
of NAD by dihydrogen in water. The results were disappointing
in terms of both catalyst lifetime (<120 min) and turnovers (∼1
+
+
with Dyeox ) MB or Saf is established by pH measurements
-
1
h ).
(4) Bhaduri, S.; Sharma, K. J. Chem. Soc., Chem. Commun. 1996, 207-
2
08.
†
Associated Cement Company.
(5) (a) Nigg, E. A. Nature 1997, 386, 779-787. (b) Voet, D.; Voet, J. G.
Biochemistry, 2nd ed.; John Wiley & Sons, Inc.: New York, 1996; pp 566-
568.
(6) Dawson, R. M. C.; Elliott, D. C.; Elliott, W. H.; Jones, K. M., Eds.
Data for Biochemical Research; Oxford University Press: New York, 1969;
pp 438-439.
(7) (a) Wong, C.-H.; Daniels, L.; Orme-Johnson, W. H.; Whitesides, G.
M. J. Am. Chem. Soc. 1981, 103, 6227-6228. (b) Thanos, I.; Simon, H.
Angew. Chem., Int. Ed. Engl. 1986, 25, 462-463. (c) Chao, S.; Wrighton, M.
S. J. Am. Chem. Soc. 1987, 109, 5886-5888.
‡
§
Indian Institute of Technology, Bombay.
Jaysynth Dye Chem Limited.
(
1) (a) S u¨ ss-Fink, G.; Meister, G. AdV. Organomet. Chem. 1993, 35, 41-
1
34. (b) Lewis, L. N. Chem. ReV. 1993, 93, 2693-2730. (c) Adams, R. D.;
Cotton, F. A., Eds. Catalysis by di and polynuclear metal cluster complexes,
Wiley-VCH: New York, 1998.
(
(
2) Longoni, G.; Chini, P. J. Am. Chem. Soc. 1976, 98, 7225-7231.
3) Basu, A.; Bhaduri, S.; Sharma, K. J. Chem. Soc., Dalton. Trans. 1984,
2
315-2318.
1
0.1021/ja982722k CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/10/1998