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NMR studies of the interaction between cytosine and gold complexes
JOURNAL
OF MAGNETIC
RESONANCE
26,43-41(1977)
NMR Studies of the Interaction between Cytosine and Gold Complexes MARIO BRESSAN, RENATO ETTORRE,* AND PIERLUICI
RIGO
Centro di Studio sulla Stabilitd e Reattivitd dei Composti di Coordinazione, Institute of Analytical Chemistry, University of Padua, Padua, Italy
Received August 8, 1976 Hydrogen-l NMR data are reported for the systems (a)cytosine-[(CsHs CH&S]AuCI, (b) cytosine
Metal complexes of purine and pyrimidine bases may serve as a model for the interaction between nucleic acids and metal ions. In a previous paper (1) we reported NMR studies of palladium(I1) and platinum(H) complexation of cytosine. In this paper we present NMR studies on the interaction of cytosine with the gold(I) complex ((C,H,* CH,)$)AuCl and the gold(III) complex anions (AuClJ and (AuBr,)- in DMSO-d, Gold(II1) is known to interact with DNA (2), and the binding of gold(II1) to adenine nucleotides has been studied (3).
k The ‘H spectrum of an equimolar mixture of 0.2 M cytosine and ((C,H,*CH,),S)AuCl shows benzylsulfide resonances at 6 = 7.30 (C,H,) and 3.74 (CH,) and a set of cytosine resonances, whose parameters are quoted in Table 1 together with data for free and platinum(II)-bonded cytosine. For the platinumsytosine system the coordination of the ligand as 4-amino-2(1H)pyrimidinone and binding through the N-3 atom have been established (1). The similarity of chemical shift values for the platinum(I1) and gold(I) systems indicates similar modes of binding to both metals. The splitting of the * Author to whom correspondence should be addressed. 43
Copyright 0 1977 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain
ISSN
0022-2364
44
BRESSAN,
ETTORRE TABLE
AND
RIG0
1
‘H NMR DATA Chemical shifts, ppm downfield from TMS
-_____ Cytosine 0.1 M Cytosine 0.1 M-cytosine HCl.O.lM
Cytosine 0.2 M-[(CsHs.CH2),S]AuCI 0.2 M Cytosine 0.2 M-PtC12 0.2 M” 5-Bromocytosine 0.05 M 5-Bromocytosine 0.05 M-H2S04
Cytosine 0.2 M-K(AuBr,,) 0.2 M’
0.5 M
H-l
NHz
-a
-.-a --.c
-c 11.30 11.29’ -g -h -j
8.50, 7.96 8.59, 8.25 -4 9.27, 9.13 -I
H-6
H-5
7.31b 7.60’ 7.57” 7.48f 7.73 8.26 8.26
5.57b 5.88b 5.85b 5.78L -
’ Unresolvedresonances.Broad asymmetricalpeak with maximum at 6 = 7.06. b Doublet. Js6 = 7 Hz. c Unresolvedresonances.Broad peak at 6 = 8.86 from H-l, H-3, and NHI. d Data from Ref. (I). e Doublet. J16= 5.5 Hz. f Apparent triplet from coupling to both H-l and H-5. g Unresolved resonances. Broad asymmetrical peak with maximum at 6 = 6.85,
h Averagedsignal from H-l, H-3, and H,SO, at 6 = 11.20. ’ Reaction time of 4 weeks. j Broad peak at 6 = 8.78. Seetext. amine resonance, due to restricted rotation around the C-NH, bond, is also consistent with coordination to gold through N-3. An increase in the double-bond character of the exocyclic C-N bond is expected as electrons are withdrawn from the cytosine ring by the metal and nonbonding electrons drawn from the amine nitrogen into the C-NH, bond. However, the appearance of a single NH2 signal would not necessarily rule out metal complexation through N-3 (I). In the spectrum of gold-bonded cytosine, spinspin coupling between H-l and H-6 protons is not observed, as for free cytosine and cytosine hydrochloride but unlike the case of palladium(I1) and platinum(I1) complexes (I). Both failure to observe H-l/H-6 coupling and the very broad nature of the NH resonances suggest the presence of some uncomplexed cytosine. Proton spectra of the system cytosine-tetrachloroaurate(II1) display several signals. However, for mixtures of 0.1 M cytosine and ((C,H,),N) (AuCl,) in the concentration range 0.06-0.4 M, two main sets of resonances are found to correspond to over 80 % of total cytosine. A first set, A, showing increasing relative intensity and slight frequency changes as the concentration of added (AuCl,)- is increased, consists of a singlet shifting in the range 9.29-9.37 ppm (linewidth of ca. 10 Hz) and two doublets at 6 = 7.66-7.62 (H-6) and 6 = 6.02-6.04 (H-5) (556 = 7 Hz). A second set of resonances, B, displaying decreasing relative intensity and downfield shifts with increased (AuCl& concentration, consists of a very broad peak with maximum shifting in the range of ca. 7.6-8.6 ppm and two doublets at 6 = 7.41-7.54 (H-6) and 6 = 5.69-5.83 (H-5) (Js6 = 7 Hz). For example, the intensities of the CH(A) and CH(B) signals are in the approximate ratios 1: 4 for 0.1 M (AuCW-, 1: 2 for 0.2 M (AuCl,)-, and 1: 1 for 0.4 M (AuCl,)-. These results indicate equilibrium conditions.
INTERACTION
OF CYTOSINE
WlTH
GOLD
COMPLEXES
45
In the proton pattern A, the resonance at 6 = 9.29-9.37 is ascribed to NH, protons on the basis of the chemical shift, lineshape, and relative intensity. Absence of a resolved H-l signal in this system led us to consider the possibility that a deprotonationcoordination equilibrium of cytosine was present, of the type (AuCI,)-
+ 2cytosine Z [(cytosine-H)AuCIJ
+ (cytosine.H)+
+ Cl-.
HI
Accordingly, the set of resonances A could be assigned as the spectrum of metalbonded deprotonated cytosine (cytosine-H), and set B as the averaged spectrum of cytosine and protonated cytosine. We have measured the spectra of a mixture of 0.1 M cytosine and O.lM cytosine hydrochloride, to which [(&H&N] (AuCl,) was added. The initial spectrum of the mixture consisted of a broad peak from H-l, H-3, and NH2 protons and doublets from H-6 and H-5 (see Table 1). The addition of the gold complex (0.1 and 0.2 M) produced a small downfield shift of these signals and the appearance of minor resonances. The formation of system A was apparent from the NH region and from the downfield peak of the H-5 doublet, other CH peaks overlapping with major signals. Comparison with corresponding experiments carried out in the absence of cytosine hydrochloride shows that the amount of system A formed is not appreciably decreased by the presence of protonated cytosine. This observation rules out the deprotonation-coordination equilibrium, as far as the main species formed are concerned. We consider that the NMR behavior of the cytosine-(AuCl,)system can be accounted for by the presence of two simultaneous equilibria: (a) The first is a ligand exchange equilibrium, slow in the NMR time scale, of the type (AuClJ
+ cytosine Z [(cytosine)AuCl,]
+ Cl-,
PI
involving metal coordination of cytosine. Accordingly, the proton pattern A is assigned to the cytosine complex. The absence of a separate H-l signal is ascribed to fast proton exchange with free base. Chemical shifts of the other protons are similar to corresponding mean values of protonated cytosine and are consistent with coordination through the N-3 atom, although a different mode of bonding cannot be completely ruled out on the basis of available information. (b) The second equilibrium is an association equilibrium, fast on the NMR time scale, involving the formation of a labile complex of cytosine. Accordingly, the proton pattern B is assigned as the averaged spectrum of free and weakly associated cytosine. The broad peak at 6 = 7.6-8.6 is ascribed to the H-l and NH, resonances of this system, which are not resolved as in the case of concentrated free cytosine, and to rapid exchange with the H-l proton of the complex [(cytosine)AuCl,]. A labile complex of cytosine might involve a charge transfer interaction between (AuClJ and the six-membered ring, or the formation of metal adducts with a coordination number greater than 4 (4), but hydrogen bonding of cytosine to a tetrachloroaurate(III) anion and/or to an uncoordinated chloride is the most probable interaction. The formation of hydrogen-bonded adducts is supported by analogous observations reported on the complexation of halide ions by cytidine and guanosine in dimethylsulfoxide (5, 6). The nucleoside-anion association equilibria reported are fast on the NMR time scale. The spectrum of a solution of 0.02 M cytosine and 0.1 A4 [(C,H,),N] (AuCl,) has been also measured. For this solution the intensities of the CH(A) and CH(B) signals
46
BRESSAN,
ETTORRE
AND
RIG0
are in the approximate ratio 2: 3. When 0.05 M NaCl was added, the intensity ratio was decreased to less than 1: 3. These results are in agreement with Eq. [2]. On the other hand, no effect of excesschloride is shown in the cytosine hydrochloride experiment (see above). This behavior could be rationalized in terms of chloride ion association with cytosine monocation (7). Minor species present in the system cytosine-(AuClJ could not be analyzed because of the low intensity of the proton signals and partial overlap with the main resonances. In the system cytosine-(AuBrJ, bromination of the base at position 5 and the reduction of gold(II1) to gold(I) are found to occur. Proton spectra of 5-bromocytosine and of the system 5-bromocytosine-H,SO, have been measured for comparison purposes (see Table 1). The spectrum of the base in acidic medium is consistent with protonation at N-3, as for the case of cytosine. In a mixture of 0.2 A4 cytosine and 0.2 M K(AuBr,), 50 % halogenation of cytosine takes place after 1 min, i.e., the time required for sample preparation and measurement. The proton spectrum of the mixture shows a singlet at 6 = 7.89 and doublets at 6 = 7.79 and 5.98. The signals are respectively assigned to H-6 of 5-bromocytosine and to H-6 and H-5 of protonated cytosine (J56 = 7 Hz), which is formed by hydrobromic acid from the halogenation reaction. A very broad complex signal is observed at lower field from H-l, H-3, and NH2 protons. After 50 % bromination has occurred, slow bromination of protonated cytosine at position 5 is shown by decreasing intensities of the H-6 and H-5 doublets and the increasing intensity of the H-6 singlet. A gradual shift to lower field of the latter resonance is due to the formation of protonated 5-bromocytosine. The reaction is not completed after 4 weeks at room temperature, when the red color of the gold(II1) complex is still apparent and 5-10 % of the protonated cytosine is left. Under these conditions the singlet observed at 6 = 8.26 is ascribed to H-6 of protonated 5bromocytosine. The NH proton resonances of the solution are not resolved, but instead, a broad peak at 6 = 8.78 is observed. An examination of chemical shift data for NH2 of protonated 5-bromocytosine (Table 1) and for H-l/H-3 protons of cytosine hydrochloride (I) suggests a contribution to the peak at b = 8.78 from proton exchange with water contained in the solvent. If cytosine and tetrabromoaurate(II1) are mixed in a molar ratio 2: 1, the total reduction of gold(III) to gold(I) is immediately observed with the formation of equimolar amounts of cytosine hydrobromide and 5bromocytosine. The H-6 resonance of the latter is again measured at 6 = 7.89; the difference from the value found for an authentic sample of 5-bromocytosine may indicate interaction of the base with gold(I). We have measured the 13C spectra, both ‘H coupled and decoupled, of the equimolar cytosine-(AuBr,)) system after a reaction time of 4 weeks. These are essentially the spectra of ca. 0.2 M protonated 5-bromocytosine. The following NMR parameters have been measured (chemical shifts in parts per million downfield from TMS): C-4, 6 = 158.6; C-2, 148.2; C-6, 147.7; C-5, 84.8 (broad signal); J(C-6/H-6) = 189 Hz; J(C-4/H-6) = J(C-2/H-6) = 7 Hz. EXPERIMENTAL
Cytosine and hexadeuterodimethyl sulfoxide (Uvasol) were obtained from Merck. Gold complexes and 5-bromocytosine were prepared by reported methods. Spectra were recorded on a Bruker WP-60 spectrometer operating at 14.09 kG in the pulse
INTERACTION
OF
CYTOSINE
WITH
GOLD
COMPLEXES
41
Fourier-transform mode. Resonances of ‘H and 13C from the sulfoxide were used as internal references and chemical shift data were referred to tetramethylsilane. REFERENCES 1. 2. 3. 4. 5. 6. 7.
F. C. D. C. C. T. J.
COLETTA, R. ETTORRE, AND A. GAMBARO, J. Magn. Resonance 22,453 (1976). K. S. PILLAI AND U. S. NANDI, Biopolymers 12,143l (1973). W. GIBSON, M. BEER, AND R. J. BARRNETT, Biochemisfry lo,3669 (1971). M. HARRIS AND I. H. REECE, Nature (London) 182,1665 (1958). H. CHANG AND L. G. MARZILLI, J. Amer. Chem. Sot. 96,3656 (1974). YOKONO, S. SHIMOKAWA, AND J. SHOMA, J. Amer. Chem. Sot. 97,3827 (1975). J. M. ROWE, J. HINTON, AND K. L. ROWE, Chem. Rev. 70,l (1970).
OF MAGNETIC
RESONANCE
26,43-41(1977)
NMR Studies of the Interaction between Cytosine and Gold Complexes MARIO BRESSAN, RENATO ETTORRE,* AND PIERLUICI
RIGO
Centro di Studio sulla Stabilitd e Reattivitd dei Composti di Coordinazione, Institute of Analytical Chemistry, University of Padua, Padua, Italy
Received August 8, 1976 Hydrogen-l NMR data are reported for the systems (a)cytosine-[(CsHs CH&S]AuCI, (b) cytosine
Metal complexes of purine and pyrimidine bases may serve as a model for the interaction between nucleic acids and metal ions. In a previous paper (1) we reported NMR studies of palladium(I1) and platinum(H) complexation of cytosine. In this paper we present NMR studies on the interaction of cytosine with the gold(I) complex ((C,H,* CH,)$)AuCl and the gold(III) complex anions (AuClJ and (AuBr,)- in DMSO-d, Gold(II1) is known to interact with DNA (2), and the binding of gold(II1) to adenine nucleotides has been studied (3).
k The ‘H spectrum of an equimolar mixture of 0.2 M cytosine and ((C,H,*CH,),S)AuCl shows benzylsulfide resonances at 6 = 7.30 (C,H,) and 3.74 (CH,) and a set of cytosine resonances, whose parameters are quoted in Table 1 together with data for free and platinum(II)-bonded cytosine. For the platinumsytosine system the coordination of the ligand as 4-amino-2(1H)pyrimidinone and binding through the N-3 atom have been established (1). The similarity of chemical shift values for the platinum(I1) and gold(I) systems indicates similar modes of binding to both metals. The splitting of the * Author to whom correspondence should be addressed. 43
Copyright 0 1977 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain
ISSN
0022-2364
44
BRESSAN,
ETTORRE TABLE
AND
RIG0
1
‘H NMR DATA Chemical shifts, ppm downfield from TMS
-_____ Cytosine 0.1 M Cytosine 0.1 M-cytosine HCl.O.lM
Cytosine 0.2 M-[(CsHs.CH2),S]AuCI 0.2 M Cytosine 0.2 M-PtC12 0.2 M” 5-Bromocytosine 0.05 M 5-Bromocytosine 0.05 M-H2S04
Cytosine 0.2 M-K(AuBr,,) 0.2 M’
0.5 M
H-l
NHz
-a
-.-a --.c
-c 11.30 11.29’ -g -h -j
8.50, 7.96 8.59, 8.25 -4 9.27, 9.13 -I
H-6
H-5
7.31b 7.60’ 7.57” 7.48f 7.73 8.26 8.26
5.57b 5.88b 5.85b 5.78L -
’ Unresolvedresonances.Broad asymmetricalpeak with maximum at 6 = 7.06. b Doublet. Js6 = 7 Hz. c Unresolvedresonances.Broad peak at 6 = 8.86 from H-l, H-3, and NHI. d Data from Ref. (I). e Doublet. J16= 5.5 Hz. f Apparent triplet from coupling to both H-l and H-5. g Unresolved resonances. Broad asymmetrical peak with maximum at 6 = 6.85,
h Averagedsignal from H-l, H-3, and H,SO, at 6 = 11.20. ’ Reaction time of 4 weeks. j Broad peak at 6 = 8.78. Seetext. amine resonance, due to restricted rotation around the C-NH, bond, is also consistent with coordination to gold through N-3. An increase in the double-bond character of the exocyclic C-N bond is expected as electrons are withdrawn from the cytosine ring by the metal and nonbonding electrons drawn from the amine nitrogen into the C-NH, bond. However, the appearance of a single NH2 signal would not necessarily rule out metal complexation through N-3 (I). In the spectrum of gold-bonded cytosine, spinspin coupling between H-l and H-6 protons is not observed, as for free cytosine and cytosine hydrochloride but unlike the case of palladium(I1) and platinum(I1) complexes (I). Both failure to observe H-l/H-6 coupling and the very broad nature of the NH resonances suggest the presence of some uncomplexed cytosine. Proton spectra of the system cytosine-tetrachloroaurate(II1) display several signals. However, for mixtures of 0.1 M cytosine and ((C,H,),N) (AuCl,) in the concentration range 0.06-0.4 M, two main sets of resonances are found to correspond to over 80 % of total cytosine. A first set, A, showing increasing relative intensity and slight frequency changes as the concentration of added (AuCl,)- is increased, consists of a singlet shifting in the range 9.29-9.37 ppm (linewidth of ca. 10 Hz) and two doublets at 6 = 7.66-7.62 (H-6) and 6 = 6.02-6.04 (H-5) (556 = 7 Hz). A second set of resonances, B, displaying decreasing relative intensity and downfield shifts with increased (AuCl& concentration, consists of a very broad peak with maximum shifting in the range of ca. 7.6-8.6 ppm and two doublets at 6 = 7.41-7.54 (H-6) and 6 = 5.69-5.83 (H-5) (Js6 = 7 Hz). For example, the intensities of the CH(A) and CH(B) signals are in the approximate ratios 1: 4 for 0.1 M (AuCW-, 1: 2 for 0.2 M (AuCl,)-, and 1: 1 for 0.4 M (AuCl,)-. These results indicate equilibrium conditions.
INTERACTION
OF CYTOSINE
WlTH
GOLD
COMPLEXES
45
In the proton pattern A, the resonance at 6 = 9.29-9.37 is ascribed to NH, protons on the basis of the chemical shift, lineshape, and relative intensity. Absence of a resolved H-l signal in this system led us to consider the possibility that a deprotonationcoordination equilibrium of cytosine was present, of the type (AuCI,)-
+ 2cytosine Z [(cytosine-H)AuCIJ
+ (cytosine.H)+
+ Cl-.
HI
Accordingly, the set of resonances A could be assigned as the spectrum of metalbonded deprotonated cytosine (cytosine-H), and set B as the averaged spectrum of cytosine and protonated cytosine. We have measured the spectra of a mixture of 0.1 M cytosine and O.lM cytosine hydrochloride, to which [(&H&N] (AuCl,) was added. The initial spectrum of the mixture consisted of a broad peak from H-l, H-3, and NH2 protons and doublets from H-6 and H-5 (see Table 1). The addition of the gold complex (0.1 and 0.2 M) produced a small downfield shift of these signals and the appearance of minor resonances. The formation of system A was apparent from the NH region and from the downfield peak of the H-5 doublet, other CH peaks overlapping with major signals. Comparison with corresponding experiments carried out in the absence of cytosine hydrochloride shows that the amount of system A formed is not appreciably decreased by the presence of protonated cytosine. This observation rules out the deprotonation-coordination equilibrium, as far as the main species formed are concerned. We consider that the NMR behavior of the cytosine-(AuCl,)system can be accounted for by the presence of two simultaneous equilibria: (a) The first is a ligand exchange equilibrium, slow in the NMR time scale, of the type (AuClJ
+ cytosine Z [(cytosine)AuCl,]
+ Cl-,
PI
involving metal coordination of cytosine. Accordingly, the proton pattern A is assigned to the cytosine complex. The absence of a separate H-l signal is ascribed to fast proton exchange with free base. Chemical shifts of the other protons are similar to corresponding mean values of protonated cytosine and are consistent with coordination through the N-3 atom, although a different mode of bonding cannot be completely ruled out on the basis of available information. (b) The second equilibrium is an association equilibrium, fast on the NMR time scale, involving the formation of a labile complex of cytosine. Accordingly, the proton pattern B is assigned as the averaged spectrum of free and weakly associated cytosine. The broad peak at 6 = 7.6-8.6 is ascribed to the H-l and NH, resonances of this system, which are not resolved as in the case of concentrated free cytosine, and to rapid exchange with the H-l proton of the complex [(cytosine)AuCl,]. A labile complex of cytosine might involve a charge transfer interaction between (AuClJ and the six-membered ring, or the formation of metal adducts with a coordination number greater than 4 (4), but hydrogen bonding of cytosine to a tetrachloroaurate(III) anion and/or to an uncoordinated chloride is the most probable interaction. The formation of hydrogen-bonded adducts is supported by analogous observations reported on the complexation of halide ions by cytidine and guanosine in dimethylsulfoxide (5, 6). The nucleoside-anion association equilibria reported are fast on the NMR time scale. The spectrum of a solution of 0.02 M cytosine and 0.1 A4 [(C,H,),N] (AuCl,) has been also measured. For this solution the intensities of the CH(A) and CH(B) signals
46
BRESSAN,
ETTORRE
AND
RIG0
are in the approximate ratio 2: 3. When 0.05 M NaCl was added, the intensity ratio was decreased to less than 1: 3. These results are in agreement with Eq. [2]. On the other hand, no effect of excesschloride is shown in the cytosine hydrochloride experiment (see above). This behavior could be rationalized in terms of chloride ion association with cytosine monocation (7). Minor species present in the system cytosine-(AuClJ could not be analyzed because of the low intensity of the proton signals and partial overlap with the main resonances. In the system cytosine-(AuBrJ, bromination of the base at position 5 and the reduction of gold(II1) to gold(I) are found to occur. Proton spectra of 5-bromocytosine and of the system 5-bromocytosine-H,SO, have been measured for comparison purposes (see Table 1). The spectrum of the base in acidic medium is consistent with protonation at N-3, as for the case of cytosine. In a mixture of 0.2 A4 cytosine and 0.2 M K(AuBr,), 50 % halogenation of cytosine takes place after 1 min, i.e., the time required for sample preparation and measurement. The proton spectrum of the mixture shows a singlet at 6 = 7.89 and doublets at 6 = 7.79 and 5.98. The signals are respectively assigned to H-6 of 5-bromocytosine and to H-6 and H-5 of protonated cytosine (J56 = 7 Hz), which is formed by hydrobromic acid from the halogenation reaction. A very broad complex signal is observed at lower field from H-l, H-3, and NH2 protons. After 50 % bromination has occurred, slow bromination of protonated cytosine at position 5 is shown by decreasing intensities of the H-6 and H-5 doublets and the increasing intensity of the H-6 singlet. A gradual shift to lower field of the latter resonance is due to the formation of protonated 5-bromocytosine. The reaction is not completed after 4 weeks at room temperature, when the red color of the gold(II1) complex is still apparent and 5-10 % of the protonated cytosine is left. Under these conditions the singlet observed at 6 = 8.26 is ascribed to H-6 of protonated 5bromocytosine. The NH proton resonances of the solution are not resolved, but instead, a broad peak at 6 = 8.78 is observed. An examination of chemical shift data for NH2 of protonated 5-bromocytosine (Table 1) and for H-l/H-3 protons of cytosine hydrochloride (I) suggests a contribution to the peak at b = 8.78 from proton exchange with water contained in the solvent. If cytosine and tetrabromoaurate(II1) are mixed in a molar ratio 2: 1, the total reduction of gold(III) to gold(I) is immediately observed with the formation of equimolar amounts of cytosine hydrobromide and 5bromocytosine. The H-6 resonance of the latter is again measured at 6 = 7.89; the difference from the value found for an authentic sample of 5-bromocytosine may indicate interaction of the base with gold(I). We have measured the 13C spectra, both ‘H coupled and decoupled, of the equimolar cytosine-(AuBr,)) system after a reaction time of 4 weeks. These are essentially the spectra of ca. 0.2 M protonated 5-bromocytosine. The following NMR parameters have been measured (chemical shifts in parts per million downfield from TMS): C-4, 6 = 158.6; C-2, 148.2; C-6, 147.7; C-5, 84.8 (broad signal); J(C-6/H-6) = 189 Hz; J(C-4/H-6) = J(C-2/H-6) = 7 Hz. EXPERIMENTAL
Cytosine and hexadeuterodimethyl sulfoxide (Uvasol) were obtained from Merck. Gold complexes and 5-bromocytosine were prepared by reported methods. Spectra were recorded on a Bruker WP-60 spectrometer operating at 14.09 kG in the pulse
INTERACTION
OF
CYTOSINE
WITH
GOLD
COMPLEXES
41
Fourier-transform mode. Resonances of ‘H and 13C from the sulfoxide were used as internal references and chemical shift data were referred to tetramethylsilane. REFERENCES 1. 2. 3. 4. 5. 6. 7.
F. C. D. C. C. T. J.
COLETTA, R. ETTORRE, AND A. GAMBARO, J. Magn. Resonance 22,453 (1976). K. S. PILLAI AND U. S. NANDI, Biopolymers 12,143l (1973). W. GIBSON, M. BEER, AND R. J. BARRNETT, Biochemisfry lo,3669 (1971). M. HARRIS AND I. H. REECE, Nature (London) 182,1665 (1958). H. CHANG AND L. G. MARZILLI, J. Amer. Chem. Sot. 96,3656 (1974). YOKONO, S. SHIMOKAWA, AND J. SHOMA, J. Amer. Chem. Sot. 97,3827 (1975). J. M. ROWE, J. HINTON, AND K. L. ROWE, Chem. Rev. 70,l (1970).