WWW.BOOK.XLIBX.INFO
FREE ELECTRONIC LIBRARY - Books, abstracts, thesis
 
<< HOME
CONTACTS

Pages:     | 1 |   ...   | 15 | 16 || 18 |

«A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of ...»

-- [ Page 17 ] --

4. Lipowska, M.; He, H.; Malveaux, E.; Xu, X.; Marzilli, L. G.; Taylor, A. T. J. Nucl. Med.

2006, 47, 1032-1040.

5. Maresca, K. P.; Marquis, J. C.; Hillier, S. M.; Lu, G.; Femia, F. J.; Zimmerman, C. N.;

Eckelman, W. C.; Joyal, J. L.; Babich, J. Biocongugate Chem. 2010, ASAP.

6. Alberto, R.; N'Dongo, H. P.; Clericuzio, M.; Bonetti, S.; Gabano, E.; Cassino, C.; Ravera, M.;

Osella, D. Inorg. Chim. Acta 2009, 362, 4785-4790.

7. Alberto, R.; Schibli, R.; Egli, A.; Schubiger, A. P.; Abram, U.; Kaden, T. A. J. Am. Chem.

Soc. 1998, 120, 7987-7988.

8. Alberto, R.; Ortner, K.; Wheatley, N.; Schibli, R.; Schubiger, A. P. J. Am. Chem. Soc. 2001, 123, 3135-3136.

9. Alberto, R.; Schibli, R.; Schubiger, A. P.; Abram, U.; Pietzsch, H. J.; Johannsen, B. J. Am.

Chem. Soc. 1999, 121, 6076-6077.

10. He, H.; Lipowska, M.; Xu, X.; Taylor, A. T.; Marzilli, L. G. Inorg. Chem. 2007, 46, 3385He, H. Y.; Lipowska, M.; Christoforou, A. M.; Marzilli, L. G.; Taylor, A. T. Nucl. Med.

Biol. 2007, 34, 709-716.

12. Desbouis, D.; Struthers, H.; Spiwok, V.; Küster, T.; Schibli, R. J. Med. Chem. 2008, 51, 6689-6698.

13. Bartholomä, M.; Valliant, J.; Maresca, K. P.; Babich, J.; Zubieta, J. Chem. Commun.

(Cambridge, U.K.) 2009, 493-512.

14. Shen, Y.; Maliwal, B. P.; Lakowicz, J. R. J. Fluoresc. 2001, 11, 315-318.

15. Guo, X.-Q.; Castellano, F. N.; Li, L.; Szmacinski, H.; Lakowicz, J. R.; Sipior, J. Anal.

Biochem. 1997, 254, 179-186.

16. Storr, T.; Fisher, C. L.; Mikata, Y.; Yano, S.; Adam, M. J.; Orvig, C. Dalton Trans. 2005, 654-655.

17. Xia, J.; Wang, Y.; Li, G.; Yu, J.; Yin, D. J. Radioanal. Nucl. Chem. 2009, 279, 245-252.

18. Banerjee, S. R.; Levadala, M. K.; Lazarova, N.; Wei, L.; Valliant, J. F.; Stephenson, K. A.;

Babich, J. W.; Maresca, K. P.; Zubieta, J. Inorg. Chem. 2002, 41, 6417-6425.

19. Maresca, K. P.; Kronauge, J. F.; Zubieta, J.; Babich, J. Inorg. Chem. Commun. 2007, 10, 1409-1412.

20. Toscano, P. J.; Jordan, K. F.; Engelhardt, L. M.; Skelton, B. W.; White, A. H.; Marzilli, P.

A. Polyhedron 1990, 9, 1079-1085.

21. Toscano, P. J.; Marzilli, L. G. Inorg. Chem. 1983, 22, 3342-3350.

22. Saladini, M.; Iacopino, D.; Menabue, L. Inorg. Biochem. 2000, 78, 355-361.

23. Christoforou, A. M.; Fronczek, F. R.; Marzilli, P. A.; Marzilli, L. G. Inorg. Chem. 2007, 46, 6942-6949.

24. Klingele, M. H.; Moubaraki, B.; Murray, K. S.; Brooker, S. Chem.-Eur.J. 2005, 11, 6962Christoforou, A. M.; Marzilli, P. A.; Marzilli, L. G. Inorg. Chem. 2006, 45, 6771-6781.

26. Caselli, A.; Cesana, F.; Gallo, E.; Casati, N.; Macchi, P.; Sisti, M.; Celentano, G.; Cenini, S.

Dalton Trans. 2008, 4202-4205.

27. Calligaris, M.; Carugo, O.; Crippa, G.; De Santis, G.; Di Casa, M.; Fabbrizzi, L.; Poggi, A.;

Seghi, B. Inorg. Chem. 1990, 29, 2964-2970.

28. Sun, C.-H.; Chow, T. J.; Liu, L.-K. Organometallics 1990, 9, 560-565.

29. Manono, J.; Marzilli, P. A.; Fronczek, F. R.; Marzilli, L. G. Inorg. Chem. 2009, 48, 5626Canovese, L.; Visentin, F.; Chessa, G.; Uguagliati, P.; Levi, C.; Dolmella, A.; Bandoli, G.

Organometallics 2006, 25, 5355-5365.

31. Meneghetti, S. P.; Lutz, P. J.; Kress, J. Organometallics 2001, 20, 5050-5055.

32. He, H.; Lipowska, M.; Xu, X.; Taylor, A. T.; Carlone, M.; Marzilli, L. G. Inorg. Chem.

2005, 44, 5437-5446.

33. Perera, T.; Fronczek, F. R.; Marzilli, P. A.; Marzilli, L. G., Manuscript in Preparation.

34. Gonsalves, A. M. R.; Johnstone, R. A. W.; Pereira, M. M.; de SantAna, A. M. P.; Serra, A.

C.; Sobral, A. J. F. N.; Stocks, P. A. Heterocycles 1996, 43, 829-838.

35. Otwinowski, Z.; Minor, W. Macromolecular Crystallography, Part A, Methods in Enzymology; New York Academic Press: New York, 1997; Vol. 276, pp. 307-326.

36. Sheldrick, G. M. "SHELXL97, Program for Crystal Structure Solution and Refinement," University of Gottingen: Gottingen, Germany, 1997.

37. Casanova, M.; Zangrando, E.; Munini, F.; Iengo, E.; Alessio, E. Dalton Trans. 2006, 5033Ghirotti, M.; Chioboli, C.; Indelli, M. T.; Scandola, F.; Casanova, M.; Iengo, E.; Alessio, E.

Inorg. Chim. Acta 2007, 360, 1121-1130.

39. Christoforou, A. M.; Marzilli, P. A.; Fronczek, F. R.; Marzilli, L. G. Inorg. Chem. 2007, 46, 11173-11182.

40. Perera, T.; Marzilli, P. A.; Fronczek, F. R.; Marzilli, L. G. Inorg. Chem. 2010, 49, 5560Perera, T.; Fronczek, F. R.; Marzilli, P. A.; Marzilli, L. G., Inorg. Chem. DOI:

10.1021/ic100714m.

–  –  –

New fac-Re(CO)3 complexes bearing tridentate chelators and a combination of bidentate and monodendate ligands have been synthesized and studied in detail.

In general, this dissertation research contributes toward advancing our understanding of fac-[Re(CO)3L]+ complexes of potential radiopharmaceutical utility. The structural and NMR spectral investigation of fac-[Re(CO)3(polyamine)]+ complexes with six-membered chelate rings has revealed that changing a dimethylene chain bridging the donor atoms to a trimethylene chain does not alter exposure of exo and endo-NH groups. The upfield signal for exo-NH’s of five and six-membered chelate rings is consistent with difference in solvent exposure.





A new conjugation approach is presented through the synthesis of novel sulfonamide ligands and their Re complexes. In these complexes, the tertiary sulfonamide N binds and this binding is favored in the fac-[Re(CO)3L]+ complexes presented in this study because it allows a facial coordination mode of a tridentate ligand with a central tertiary sulfonamide N donor. Our results show that a sulfonamide can be used to conjugate the fac-{Re(CO)3}+ unit to a porphyrin.

We believe this method could be used to conjugate other molecules to such a core and that this chemistry may be extended to 99mTc analogues.

In general, work presented in this dissertation will help guide successful design and evaluation of diagnostic and therapeutic radiopharmaceuticals.

–  –  –

A.1 NMR Signal Assignments for [Re(CO)3(N,N-Me2dipn)]BF4 (3), [Re(CO)3(dipn)]BF4 (1), ′ [Re(CO)3(N′-Medipn)]PF6 (2), [Re(CO)3(aepn)]PF6 (6), [Re(CO)3(trenH)](PF6)2 (4), and [Re(CO)3(tacn)]PF6 (7) [Re(CO)3(N,N-Me2dipn)]BF4 (3, Figure 2.2) is a chiral complex with an unsymmetrical coordinated htL in which dynamic motion cannot interchange the rings, as was the case in previous studies (see main text). Thus 3 is a good example for initiating this detailed discussion of the assignment strategy. The ring of 3 with the terminal NH2 group has the chair conformation.

The expected three NH signals (central NH and terminal NH2) were observed for 3 in DMSO-d6 (Table 2.4, Figures A.1 and A.3). The upfield NH signal (3.78 ppm) has a COSY cross-peak (Figure A.3) to another NH signal (5.53 ppm), assigning these as the signals of the coordinated terminal NH2 group; these NH signals have a COSY cross-peak with a different CH signal.

According to the Karplus equation, the coupling between two protons connected by three bonds is larger the greater the difference between the torsion angle relating the two protons and 90°.1 The relevant H–N–C–H torsion angle for 3 (Figure A.2, Table A.1) differs more from 90° for the exo-NH (∼174°) than for the endo-NH (∼47°). The stronger NH-CH COSY peak allowed assignment of the upfield 3.78 ppm signal to the exo-NH, and the weaker NH-CH cross-peak allowed assignment of the 5.53 ppm signal to the endo-NH. The NH-CH cross-peaks allowed assignment of the methylene CH signals (endo-CH 2.80 and exo-CH 3.24 ppm). In summary, although the chelate ring has six members, the exo-NH shift is upfield, as found for 5-membered chelate rings. However, the exo-NH-endo-CH COSY cross-peak is larger than the endo-NH-exoCH COSY cross-peak, unlike the case of the 5-membered chelate ring of [Re(CO)3(tmbSO2dien)] in a previous study in which the largest H-N-C-H torsion angle was ∼157° for a ring in the exo-C conformation (Figure 2.5). For this compound, the endo-NH-exo-CH cross-peak was the strongest HN-CH cross-peak.2 For [Re(CO)3(dipn)]BF4 (1) in DMSO-d6, a COSY cross-peak between two NH signals (each integrating to 2 protons) assigned these as terminal NH2 signals (the third NH peak at 6.01 ppm, integrating for one proton, did not correlate with any NH peaks, assigning it to the central NH). The two rings are equivalent on the NMR time scale. However, the atom numbering scheme for 1 (Figure A.2) is complicated because the two rings have different conformations and are not equivalent in the solid state. Nevertheless, the largest H-N-C-H torsion angles for both rings (Table A.1) predict strong exo-NH-endo-CH coupling as for 3. The NH-CH COSY crosspeak intensities allowed assignment of the 3.78 ppm NH signal to the exo-NH and the multiplet at 2.62 ppm to endo-CH and assignment of the 5.22 ppm NH signal to the endo-NH and the multiplet at 3.2 ppm to exo-CH. An endo-NH-endo-CH cross-peak and an exo-NH-exo-CH cross-peak (both smaller than the exo-NH-endo-CH cross-peak) were also seen. The CH2 signals of 1 in acetonitrile-d3 at 3.23 (exo-CH) and 2.92 (endo-CH) ppm were assigned by using a similar procedure (NH signals in acetonitrile-d3 are given in Table 2.4). The COSY spectrum of [Re(CO)3(N′-Medipn)]PF6 (2) in DMSO-d6 (not shown) has an NH-NH cross-peak identifying the two terminal NH2 signals. The largest H-N-C-H torsion angle of the N2,N3 ring (Table A.1 and Figure A.2) predicts a strong exo-NH-endo-CH coupling. The exo-NH signal at 3.80 ppm has a strong cross-peak to a CH multiplet (2.65 ppm).

A COSY experiment on [Re(CO)3(aepn)]PF6 (6) in DMSO-d6 showed correlations between two sets of NH peaks: at 4.07 and 5.50 ppm; and at 3.50 and 5.24 ppm. Because one CH signal is so far upfield (1.74 ppm), it can be assigned to the central CH2 group. This signal has strong coupling to a 1.94 ppm signal, indicating geminal coupling. This 1.94 ppm CH signal of the central CH2 group has a strong cross-peak to a CH signal at 2.55 ppm. Because the largest torsion angle (172°) is between the endo-CH and the exo-CH of the central CH2, this 1.94 ppm signal is assigned to the exo-CH. In turn the CH signal at 2.55 ppm assigned as an endo-CH signal exhibits strong coupling to the NH signal at 3.50 ppm, identifying it as the exo-NH of the 6-membered ring of 6. This coupling to the CH2 signals leaves no doubt about the assignment of the NH’s of the 6-membered ring.

As above, from the torsion angles (170° and 179°) obtained from the molecular structure, the exo-NH signals will give the largest NH-CH COSY cross-peaks. Indeed, the upfield NH signal for each ring has a strong cross-peak to a CH signal, assigning these signals to the exoNH’s and endo-CH’s. The pucker of the 5-membered ring is endo-C in the solid, and the COSY peak confirms this conformation in solution.

For [Re(CO)3(trenH)](PF6)2 (4) in DMSO-d6, the most downfield NH signal (7.70 ppm), which showed no cross-peaks with the other NH signals, immediately disappeared upon addition of D2O. This rapid NH to ND exchange assigns this signal to the NH3+ in the dangling group.

The upfield NH signal (4.22 ppm) has a COSY cross-peak (Figure A.4) to a moderately downfield NH signal (5.62 ppm). Both of these signals of the terminal amine have moderately strong COSY cross-peaks to two CH signals. Thus, we are able to assign the CH signals to the CH2 groups adjacent to the NH2 groups. Because the cation is unsymmetrical in the solid state (Figure 2.3), the two rings are not equivalent in the crystal. The H-N-C-H torsion angles (Table A.1) predict strong COSY NH-CH cross-peaks involving the exo-NH for one ring and the endoNH for the other ring. However, as noted (see main text), both chelate rings will time average between endo-C and exo-C conformations in solution. Thus, as expected for a symmetrical complex with two 5-membered rings, the NH-CH COSY cross-peaks have similar intensity and do not allow assignment of the signals to a specific proton (Figure A.4). However, we can use the clear pattern that the upfield NH signal arises from the exo-NH to assign the NH signals of 4 (Table 2.4).

Shifts in acetone-d6 are more upfield than in other solvents for the dangling NH3+ group of 4 and 5. For 4, a COSY experiment in acetone-d6 showed that an upfield NH signal (exo) and the downfield NH signal (endo) correlate, while an upfield NH signal showed no cross-peaks with the other NH signals, assigning this latter upfield signal to the dangling NH3+ signal.

No COSY data were needed for [Re(CO)3(tacn)]PF6 (7) because the three NH’s are identical.

Figure A.1. 1H NMR spectra of [Re(CO)3(dipn)]PF6 (1), [Re(CO)3(N′-Medipn)]PF6 (2), [Re(CO)3(N,N-Me2dipn)]BF4 (3), [Re(CO)3(aepn)]PF6 (6), and [Re(CO)3(trenH)](PF6)2 (4), and [Re(CO)3(trpnH)](PF6)2 (5) in DMSO-d6 at 25 °C (* water and solvent residual peaks).

Table A.1. Selected Torsion Angles (deg) for [Re(CO)3(dipn)]BF4 (1), [Re(CO)3(N′Medipn)]PF6 (2), [Re(CO)3(N,N-Me2dipn)]BF4 (3) [Re(CO)3(trenH)](PF6)2 (4), and [Re(CO)3(aepn)]PF6 (6).

–  –  –

Figure A.2. Drawing of the cations of [Re(CO)3(dipn)]BF4 (1), [Re(CO)3(N′-Medipn)]PF6 (2), [Re(CO)3(N,N-Me2dipn)]BF4 (3) [Re(CO)3(trenH)](PF6)2 (4), and [Re(CO)3(aepn)]PF6 (6) showing the torsion angle between N3H and C4H. H31 and H12 are designated as exo-NH. Large torsion angles for exo-NH and small torsion angles for endo-NH were observed for 1, 3, and 6.

Figure A.3. 1H-1H COSY NMR spectrum of [Re(CO)3(N,N-Me2dipn)]BF4 (3) in DMSO-d6 at 25 °C.

Figure A.4. 1H-1H COSY NMR spectrum of [Re(CO)3(trenH)](PF6)2 (4) in DMSO-d6 at 25 °C.

Figure A.5. Effect of Cl– on the change in chemical shift (∆δ, ppm) of the NH signals of [Re(CO)3(trenH)](PF6)2 (4) in DMSO-d6 at 25 °C. The metal complex concentration was maintained at 5 mM throughout the titration. Addition of up to 300 mM Cl– produced no further increase in ∆δ.

Figure A.6. Effect of Cl– on ∆δ of the NH signals of [Re(CO)3(trpnH)](PF6)2 (5) in DMSO-d6 at 25 °C.

Figure A.7. Effect of Cl– on ∆δ of the NH signals of [Re(CO)3(dipn)]PF6 (1) in acetonitrile-d3 at 25 °C (top, left) and in the presence of 50 mM Et4NPF6 (top, right). An overlay of these two plots is also shown (bottom, middle).

Figure A.8. Effect of Br– on ∆δ of the NH signals of [Re(CO)3(dipn)]PF6 (1) in acetonitrile-d3 at 25 °C.



Pages:     | 1 |   ...   | 15 | 16 || 18 |


Similar works:

«BIOMECHANICAL EVALUATION OF MODIFIED TRACK SHOES A Thesis Submitted to the Graduate Faculty of the Louisiana State University and Agricultural Mechanical College in partial fulfillment of the requirements for the Degree of Master of Science in Industrial Engineering in The Department of Construction Management and Industrial Engineering By Marlon Alberetos Greensword B.S., L.S.U., 2007 B.A., L.S.U., 2005 May 2010 ACKNOWLEDGMENTS I must first give thanks to God the Father, Jesus the Son and the...»

«Sophie Spencer Director CPRE Avonside Poole Court, Yate director@cpreavonside.org.uk Campaign to Protect Rural England, Avonside branch Response to Bath Park and Ride Consultation October 2015 Summary CPRE Avonside is strongly opposed to a further park and ride facility being introduced to the East of Bath. It would cause serious damage to the Avon Green Belt, and be a negative visual intrusion on the Cotswold AONB and the Bath World Heritage City. We feel that the supposed benefits of a park...»

«Connecting Across Language and Distance: Linguistic and Rural Access to Legal Information and Services Karen Cohl and George Thomson December 2008 Connecting Across Language and Distance: Linguistic and Rural Access to Legal Information and Services Final report of the Linguistic and Rural Access to Justice Project This is the report of the Linguistic and Rural Access to Justice Project conducted by Karen Cohl and George Thomson at the request of The Law Foundation of Ontario. We would like to...»





 
<<  HOME   |    CONTACTS
2016 www.book.xlibx.info - Free e-library - Books, abstracts, thesis

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.