Supporting Information

Transcription

1 Supporting Information Wiley-VCH Weinheim, Germany

2 Dipositively Charged Protonated a 3 and a 2 Ions: Generation by Fragmentation of [La(GGG)(CH 3 CN) 2 ] 3+ Tujin Shi a, Chi-Kit Siu, K. W. Michael Siu, and Alan C. Hopkinson* Department of Chemistry and Centre for Research in Mass Spectrometry, York University 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3 Supporting Information a current address: Centre for Research in Neurodegenerative Diseases, University of Toronto P.1

3 Content: Page P.3 Full author list for reference 10a P.4 Figure S1. CID of [La(GGG)(CH 3 CN)] 3+ at collision energy E lab of 30 ev. P.5. Figure S2. CID of (a) [La(d 5 -GGG)(CH 3 CN) 2 ] 3+ (b) [La(G(α,α-d 2 -G)G)(CD 3 CN) 2 ] 3+ at collision energy E lab of 30 ev. P.6 Figure S3. CID of (a 3 + H) 2+ generated from (a) d 5 -GGG, (b) GG(G- 15 N) at collision energy E lab of 20 ev. P.7 Figure S4. CID of (a) [La(AAA)(CH 3 CN) 2 ] 3+ at collision energy E lab of 30 ev; (b) (a 3 + H) 2+ generated from AAA at collision energy E lab of 20 ev. P.8 Figure S5. CID of (a) [La(GAA)(CH 3 CN) 2 ] 3+ at collision energy E lab of 30 ev; (b) (a 3 + H) 2+ generated from GAA at collision energy E lab of 20 ev. P.9 Figure S6. Profile for generation of (a 3 + H) 2+ from [La(GGG)(CH 3 CN) n ] 3+. The energies, in kcal mol -1 ( H 0, upper number; G 298, lower number), are evaluated at the B3LYP level. The G(d,p) basis set is used for the main group elements, and the Stuttgart/Cologne relativistic effective core potential basis set for lanthanum. P.10 Figure S7. Profiles for fragmentation of (a 3 + H) 2+. (a) Formation of a 2 via b 2 *; (b) Formation of b 2. Energies, in kcal mol -1 ( H 0, upper number; G 298, lower number), are evaluated at the B3LYP/ G(d,p) level. P.11 RRKM kinetics studies for the fragmentation of the protonated a 3 ion, (a 3 + H) 2+ P.14 Car-Parrinello Molecular Dynamics (CPMD) Metadynamics (MTD) P.17 Table S1. Cartesian coordinates of structures shown in Scheme 2 and Figure S2. The geometries are optimized at the B3LYP level. The G(d,p) basis set is used for the main group elements, and the Stuttgart/Cologne relativistic effective core potential basis set for lanthanum. P.21 Table S2. Cartesian coordinates of structure shown in Scheme 3 and Figure S3a. The geometries are optimized at the B3LYP/ G(d,p) level. P.23 Table S3. Cartesian coordinates of structure shown in Scheme 2 and Figure S3b. The geometries are optimized at the B3LYP/ G(d,p) level. P.2

4 Full author list for reference 10a: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; and Pople, J. A.; Gaussian 03, Revision D.01, Gaussian, Inc., Wallingford CT, P.3

5 6.0e4 (a 3 + H) e4 5.0e4 4.5e4 4.0e4 Intensity, cps 3.5e4 3.0e4 2.5e4 2.0e4 1.5e4 1.0e a [La(GGG)(CH 3 CN)] 3+ * [LaO] + b [La(GGG - H)] [LaO(CH 3 CN)] m/z, amu Figure S1. CID of [La(GGG)(CH 3 CN)] 3+ (m/z 123) at collision energy E lab of 30 ev. P.4

6 9.5e5 [La(d 5 -GGG D)] e5 [La(d 5 -GGG CO D 2 O)] e5 [La(d 5 -GGG CO)] 2+ Intensity, cps 6.5e5 5.5e5 4.5e5 [CH 3 CN + D] [(a 3 + D) DHN=CH 2 ND 3 ] + [LaO] + [CH 3 CN + H] + 3.5e5 2.5e (a 3 + D) [La(d 5 -GGG D) D 2 N=CH 2 CO DNCO] + 1.5e5 5.0e4 a 2 a 2 * 90.0 b 2 [LaO(CH 3 CN)] b 2 * [La(d 5 -GGG D) D 2 N=CH 2 ] m/z, amu Figure S2a. CID of [La(d 5 -GGG)(CH 3 CN) 2 ] 3+ (m/z 138.4) at collision energy E lab of 30 ev. 2.6e5 [La(GG*G H)] e5 cps 2.2e5 [La(GG*G H) CO] 2+ Intensity, cps 1.8e5 1.4e5 1.0e5 [CD 3 CN + H] [La(GG*G)(CD 3 CN)] 3+ (a 3 + H) [LaO] + [La(GG*G H)(H 2 O)] 2+ [La(GG*G H)(L)] e4 2.0e a 2 * a b b * [LaO(CD 3 CN)] + [La(GG*G H) H 2 N=CH 2 ] m/z, amu Figure S2b. CID of [La(G(α,α-d 2 -G)G)(CD 3 CN) 2 ] 3+ (m/z 139.4) at collision energy E lab of 30 ev (G* = α,α-d 2 -G). P.5

7 Figure S3a. CID of (a 3 + D) 2+ (m/z 75) generated from d 5 -GGG at collision energy E lab of 20 ev. Figure S3b. CID of (a 3 + H) 2+ (m/z 73) generated from GG(G- 15 N) at collision energy E lab of 20 ev. P.6

8 1.4e6 1.3e6 1.2e6 1.1e6 1.0e6 9.0e [La(AAA H)] 2+ Max. 1.4e6 cps. Intensity, cps 8.0e5 7.0e5 6.0e5 5.0e5 4.0e5 3.0e5 2.0e5 1.0e5 [(GAA CO [La(AAA H)(CD 3 CN)] 2+ 2 ) H 2 N=CHCH 3 NH 3 ] [La(AAA H) H 2 N=CHCH 2 CO H 2 O] + + H 2 O [La(AAA H) H 2 N=CHCH 2 CO] + [(AAA CO 2 ) H 2 N=CHCH 3 CO] [La(AAA H) H 2 N=CHCH 2 ] + [LaO(CD CN)] [CD 3 CN + H] (a 3 + H) 2+ [LaO] * m/z, amu Figure S4a. CID of [La(AAA)(CD 3 CN) 2 ] 3+ (m/z 152.8) at collision energy E lab of 30 ev. 2.2e6 [H 2 N=CHCH 3 ] [(AAA CO 2 ) H 2 N=CHCH 3 NH 3 ] e6 cps Intensity, cps 1.8e6 1.4e6 [(AAA CO 2 ) H 2 N=CHCH 3 2CO] + a 2, [(AAA CO 2 ) H 2 N=CHCH 3 CO] e6 6.0e5 2.0e5 [(AAA CO 2 ) NH 3 ] 2+ (a 3 + H) 2+ [AAA CO 2 ] 2+ (a 2 + H) [AA CO 2 ] b 2, [(AAA CO 2 ) H 2 N=CHCH 3 ] m/z, amu Figure S4b. CID of (a 3 + H) 2+ (m/z 93.5) generated from AAA at collision energy E lab of 20 ev. P.7

9 1.20e6 [CD 3 CN + H] [La(GAA H)] [(GAA CO 2 ) H 2 N=CHCH 3 NH 3 ] + 1.2e6 cps 1.00e6 8.00e5 [(GAA CO 2 ) H 2 N=CHCH 3 CO] + [La(GAA H) CO] 2+ [La(GAA H) H 2 O] 2+ Intensity, cps 6.00e5 4.00e5 2.00e5 (a 3 + H) [LaO] * [La(GAA H)(H 2 O)] 2+ [La(GAA H) H 2 N=CH 2 CO H 2 O] + [LaO(CD 3 CN)] [La(GAA H) H 2 N=CH 2 ] m/z, amu Figure S5a. CID of [La(GAA)(CD 3 CN) 2 ] 3+ (m/z 148) at collision energy E lab of 30 ev. 6.5e5 [H 2 N=CHCH 3 ] a 2, [(GAA CO 2 ) H 2 N=CHCH 3 CO] + 6.7e5 cps Intensity, cps 5.5e5 4.5e5 3.5e [(GAA CO 2 ) H 2 N=CHCH 3 NH 3 ] e5 1.5e5 5.0e4 (a 3 + H) 2+ (a 2 + H) 2+ [GAA CO 2 ] 2+ [GA CO 2 ] b 2, [(GAA CO 2 ) H 2 N=CHCH 3 ] m/z, amu Figure S5b. CID of (a 3 + H) 2+ (m/z 86.6) generated from GAA at collision energy E lab of 20 ev. P.8

10 = La = H = C = N = O B 0 A 0 -TS-1 A CH 3 CN B 1 -TS-1 A 1 -TS (a 3 + H) 2+ + LaO + + CO + 2 CH 3 CN B B 2 -TS CH 3 CN CH 3 CN CH 3 CN A CH 3 CN A 2 -TS CH 3 CN CH 3 CN CH 3 CN (a 3 + H) 2+ B 2 A H 0 = 0.0 G 298K = 0.0 [b 3 + H] [LaO(CH 3 CN) 2 ] + + [LaO(CH 3 CN) 2 ] + + [LaO(CH 3 CN) 2 ] + + CO Figure S6. Profile for generation of (a 3 + H) 2+ from [La(GGG)(CH 3 CN) n ] 3+. The energies, in kcal mol -1 ( H 0, upper number; G 298, lower number), are evaluated at the B3LYP level. The G(d,p) basis set is used for the main group elements, and the Stuttgart/Cologne relativistic effective core potential basis set for lanthanum. P.9

11 Figure S7. Profiles for fragmentation of (a 3 + H) 2+. (a) Formation of a 2 via b 2 *; (b) Formation of b 2. Energies, in kcal mol -1 ( H 0, upper number; G 298, lower number), are evaluated at the B3LYP/ G(d,p) level. P.10

12 RRKM kinetics studies for the fragmentation of the protonated a 3 ion, (a 3 + H) 2+ The theoretical branching ratios of the three competitive dissociation channels of the protonated a 3 ion, (a 3 + H) 2+, formed from G(α,α-d 2 -G)G (Figure 2b and Scheme 3) are calculated using the RRKM model. The k 1 and k 2 are the rate constants for the formation and the subsequent fragmentations of b 2 * (P 1 = m/z 116, 99, 88, 60, 31, 30) and b 2 (P 2 = m/z 117, 89, 61, 32, 30), respectively. The k 3 is the rate constant for the generation of (a 2 + H) 2+ (P 3 = m/z 45). k 1 P 1, b 2 * (m/z 116, 99, 88, 60, 31, 30) k R (a 3 + H) 2+ 2 P 2, b 2 (m/z 117, 89, 61, 32, 30) k 3 P 3, (a 2 + H) 2+ (m/z 45) ev P 3, (a 2 + H) 2+ + HN=CH 2 + CO ev ev ev P 1 P 2 TS(I II) 0.0 ev R (a 3 + H) 2+ TS(I IX ) Figure S8. The energy profiles of the three competitive dissociation channels of (a 3 + H) 2+, H 3 N + CH 2 CONHCD 2 CONH + =CH 2. In the RRKM model, the rate constant k RRKM at an internal energy E of a unimolecular dissociation is calculated by the Equation (1): k RRKM ( E) ( E E ) * σ W o = (1) h ρ( E) h is the Planck s constant. The degeneracy of dissociation σ is one for k 2 and k 3 and two for k 1 which involves two deuteriums at the middle Gly residue. ρ(e) is the density of vibrational states of the reactant P.11

13 R, (i.e. (a 3 + H) 2+ ) at an internal energy E. W*(E) is the sum of vibrational states of the transition structures from the activation energy E o to the energy E. The transition structures and the activation energy E o for the formation of b 2 * and b 2 ions are TS(I II) ( H 0 = ev) and TS(I IX ) ( H 0 = ev), respectively. No transition structure can be located for the generation of (a 2 + H) 2+ (k 3 ). In order to calculate RRKM rate constant for k 3, the vibrational frequencies for a transition structure corresponding to a CO loss from a H 3 N + CH 2 CONHCD 2 CO + LNH=CH 2 complex with energy barrier of H 0 = ev (Figure S8) is used to estimate the W*(E) and the dissociation enthalpy H 0 = ev is used as the activation energy E o. (a) 1.E+14 krrkm(e ) 1.E+12 1.E+10 1.E+08 k 1 k 2 k 3 (b) 1.E Energy E / ev R, (a 3 + H) 2+ Relative abundance P 1, b 2 * P 3, (a 2 + H) 2+ P 2, b Energy E / ev Figure S9. (a) The theoretical energy solved rate constants for the dissociation channels 1, 2 and 3 modeled by the RRKM theory; (b) The theoretical abundance of (a 3 + H) 2+ and the sum of products corresponding to the dissociation channels 1 (P 1 ), 2 (P 2 ), and 3 (P 3 ) at a reaction time of 10 µs. P.12

14 Figure S9(a) shows that the formation of b 2 * ion (k 1 ) is faster than that of b 2 ion (k 2 ) which is attributed to the difference in activation entropy of k 1 ( S 298 = 7.27 cal mol -1 K -1 ) and k 2 ( S 298 = 3.76 cal mol -1 K -1 ). The formation of (a 2 + H) 2+ (k 3 ) becomes competitive at energies > 16 ev regime because of its large activation entropy ( S 298 = 14.1 cal mol -1 K -1 ). Figure S9(b) shows the relative abundance of R, P 1, P 2, P 3 (Equations 2 5) as a function of internal energy E based on the first-order rate law with a reaction time t assumed as 10 µs (approximate residence time of ions in our instrument). ( k k2 k3 )t A e P = (2) k ( k1+ k 3 ) ( 1 ) 2 + k t e = 1 1 k1 + k2 + k (3) 3 P k ( k1+ k 3 ) ( 1 ) 2 + k t e = 2 2 k1 + k2 + k (4) 3 P k ( k1+ k 3 ) ( 1 ) 2 + k t e = 3 3 k1 + k2 + k (5) 3 The theoretical abundances obtained by RRKM calculations (Figure S9b) are in reasonable agreement with the results shown in the energy resolved CID (Figure S10); the fragment ions originally from the b 2 * ion are higher in abundance that those from b 2 ion. The formation of (a 2 + H) 2+ is a higher energy process which only occurs at high collision energy. This reaction is facilitated in our instrument in which there are on average approximately 40 collisions per (a 3 + H) 2+ ion. (a 3 + H) 2+ (a 2 + H) 2+ Figure S10. Energy-resolved CID of (a 3 + H) 2+. P.13

15 Car-Parrinello Molecular Dynamics (CPMD) Metadynamics (MTD) To simulate the dissociation of (a 3 + H) to (a 2 + H) 2+ plus two neutral molecules CO and HN=CH 2 using the CP-MTD approach, two collective variables (CVs) s = {s i } were chosen which are the C-N and C-C α bonds at the amide bond between the second and third residues. The interatomic bond distance r i was transformed by Equation (6), with parameters r c = 1.8 Å, p = 6, and q = 12, which decay from 1 to 0 with the increasing r i (i.e. bond dissociation) (Figure S11). s i r i 1 r c = r i 1 r c p q (6) s (ri ) Interatomic distance r i / Å Figure S11. The shape of the Equation (6) as a function of interatomic distance r i ; C-N or C-C α distance in this study. The CVs (s(c-n) and s(c-c α ) were coupled to the dynamics of the physical system σ(r) by extending the Car-Parrinello Lagrangian L CP. [1,2] L = L [ ( R ) ] 2 CP + M s& i i ki σ i si V ( t,s) (7) 2 2 i i The second term of Equation (7) is the kinetic energy of the CVs with fictitious masses M i. The CVs, s i, force the σ i (R) to stay close and fluctuate around the value of s i by a harmonic potential term (the third term) with coupling force constants k i. The V(t,s) is a history-dependent potential, P.14

16 Equation (8), which is constructed by summing a series of Gaussian functions updated successively in a time interval t. j 2 j+ 1 j j ( s s ) ( ) ) ( s s ) ( s s ) t, = Wi exp exp 2 2 s (8) V < 4 t t 2( s ) 2( s j j ) The shape of the Gaussian hills is determined by the height W i and the width s i, and also the width along the trajectory determined by the CV-space s i. s j = j+ 1 j ( si si ) i 2 Applying the biasing potential V(t,s), a system is forced to escape a minimum and toward the lowest transition barrier on the free energy surface F(s), which can be reconstructed from the V(t,s) after the event is occurred. That is, limv ( t, s) = F( s) t (9) (10) For the CP-MTD studies, an ion was placed in a cubic box with dimension of 16 Å. The energy was evaluated using the HCTH/120 DFT functional. [3] Troullier-Martins pseudopotentials [4] were used and the wavefunctions were expanded by a planewave basis set with an energy cutoff of 70 Rydberg. The initial dynamics of an ion, the (a 3 + H) 2+, was equilibrating at a temperature of 300 K ± 100 K using the Car-Parrinello Molecular Dynamics [1] for around 2 ps with an integration time step of 4 a.u. (~0.097 fs) and a fictitious electron mass of 500 amu. A further 4.8 ps simulation ( time steps) was performed with the average temperature of the ion kept at 300 K by a chain of Nosé-Hoover thermostat. [5,6] The CVs, described above, were then introduced and the fictitious masses M i and the coupling force constant k i were 50 amu and 3 a.u. A 2 ps MTD run was performed without update of the V(t,s). Then the actual MTD simulation was performed by applying a Gaussiantype function (Equation (8)) in a time interval of MD steps. The width of the Gaussian function s i is 0.05 a.u. and the height W i between kcal mol -1 tuned according to the curvature of the underlying potential. The width of the Gaussian hills along the trajectory s i fluctuates in the interval The CV space was closed to the physical system space with a maximum absolute deviation and root mean square deviation of the difference s i (R) s i of 0.1 and 0.04, respectively, for s(c-n), and 0.13 and 0.04, respectively, for s(c-c α ). The two- P.15

17 dimensional free energy surface in the CV space was then constructed with Equation (8) after both C-N and C-C α were completely broken. The free energy surface was reconstructed based on Equation (8). The one-dimensional free energy surface with respectively to the CVs, s(c-n) and s(c-c α ), are shown in Figure S12. The barrier is 35 kcal mol -1 for the CLN bond dissociation (s(c-n) = ~0.9 to s(c-n) = ~0.25). The overall dissociation barrier is 37 kcal mol -1 (s(c-c α ) = ~0.9 to s(c-c α ) = ~0.4). 0 s (C-N) s (C-C α ) Free energy / kcal mol Free energy / kcal mol Figure S12. Free energy surface of s(c-n) and s(c-c α ). [1] R. Car, M. Parrinello, Phys. Rev. Lett. 1985, 55, 2471 [2] M. Iannuzzi, A. Laio, M. Parrinello, Phys. Rev. Lett. 2003, 90, [3] F. A. Hamprecht, A. J. Cohen, D. J. Tozer, N. C. Handy J. Chem. Phys. 1998, 109, 626 [4] Troullier, J. L. Martins, Phys Rev. B 1991, 43, [5] S. Nosé, J. Chem. Phys. 1984, 81, 511; Mol. Phys. 1984, 52, 255. [6] W. G. Hoover, Phys. Rev. A 1985, 31, P.16

18 Table S1. Cartesian coordinates of structures shown in Scheme 2 and Figure S2. The geometries are optimized at the B3LYP level. The G(d,p) basis set is used for the main group elements, and the Stuttgart/Cologne relativistic effective core potential basis set for lanthanum A2 H0= G298= B2 H0= G298= C C H C N H C O O O N H H La C H C N O C O C H O La H H N H H C C O O H C C H H H H N N H H H H H H H N N N N C C C C C C C C H H H H H H H H H H H H A2-TS-1 H0= G298= A2-TS-2 H0= G298= C C H H N N C C O O N N H H C C C C O O O O H H La La H H H H C C O O H H C C P.17

19 H H H H N N H H H H H H N N C C C C H H H H H H C C N N C C H H H H H H A1 H0= G298= B1 H0= G298= C C H C N H C O O O N H H La C H C N O C O C H O La H H N H H C C O O H C C H H H H N N H H H H H H H N N C C C C H H H H H H A1-TS-1 H0= G298= A1-TS-2 H0= G298= C C H H N N C C O O N N H H C C C C O O O O H H P.18

20 La La H H H H C C O O H H C C H H H H N N H H H H H H C N N C C C H H H H H H A0 H0= G298= B0 H0= G298= C C H C N H C O O O N H H La C H C N O C O C H O La H H N H H C C O O H C C H H H H N N H H H H H H H A0-TS-1 H0= G298= [b3 + H]2+ H0= G298= C N H H N C C C O H N H H O C H C N O H O C H C La H H H H O C N O H P.19

21 H C C C H H H H N O H H H H [b3 + H]2+ loss CO(TS) H0= G298= [a3+ H]2+ H0= G298= N N H H C C C C H H H H O O H H N N H H C C C C H H H H O O N N H H C C C H H H H H O H [LaO(CH3C N)2]+ H0= G298= [LaO(CH3C N)]+ H0= G298= O O La La N N N C C C C H C H C H H H LaO+ H0= G298= H O H La H H P.20

22 Table S2. Cartesian coordinates of structure shown in Scheme 3 and Figure S3a. The geometries are optimized at the B3LYP/ G(d,p) level I H0= G298= TS(I-II') H0= G298= N N H H C C C C H H H H O O H H N N H H C C C C H H H H O O N N H H C C H H H H H H II' H0= G298= II H0= G298= N N H C C C C H H H H O O H H N N H H C C C C O H H H H O H N H C H H H TS(II-III) H0= G298= III H0= G298= N N C C C C H H H H O O H H N N H H C C C C O O H H P.21

23 H H H H TS(III-IV) H0= G298= IV H0= G298= N C C C C H H H H O O N H H N C H C C O C H O H H H TS(II-V) H0= G298= V H0= G298= N N C C C C H H H H O O H H N N H H C C C C O O H H H H H H TS(V-VI) H0= G298= VI H0= G298= N N C C C C H H H H O O H H N N H H C C C C O O H H H H H H TS(VI-VII) H0= G298= VII H0= G298= N N H H C C C C H H H H O O H H P.22

24 N N H H C C H H H H C O TS(VII-VIII) H0= G298= VIII H0= G298= N N H H C C C C H H H H O O H H N N H H C C H H H H Table S3. Cartesian coordinates of structure shown in Scheme 2 and Figure S3b. The geometries are optimized at the B3LYP/ G(d,p) level TS(I-IX') H0= G298= X' H0= G298= N N H H C C C C H H H H O O H H N N H H C C C C H H H H O O N N H H C C H H H H H H IX H0= G298= TS(IX-X) H0= G298= N N H H C C C C H H H H O O H H N N C C C C H H P.23

25 H H O O H H X H0= G298= TS(X-XI) H0= G298= N N H H C C C C H H H H O O H H N N C C C C H H H H O O H H XI H0= G298= XII H0= G298= N C H C C H C H H O H N O C H C N H H H C O C H H O P.24