Biomedicine and Chemical Sciences
2022, Volume 1, Issue 2 : 47-56 doi: https://doi.org/10.48112/bcs.v1i2.85
Research Article
Design and Synthesis Ligands Tetradents Substituted with Halogenes in α- Position and Conjugation with Riboflavin (Bioconjugates)
Published
April 1, 2022
Abstract

In this article, we describe the process of binding riboflavin to a simple tetradents ligand substituted in α- position from TPAs types, by reacting bromotetraacetate riboflavin with α- substituted TPA with one of the pyridine rings by nitrile group and the two other pyridine rings by halogen atoms. This type of ligands showed very important properties for the activation and transfer of oxygen to a substrate in presence of iron salt. After the tetradents were obtained, the nitrile group was reduced to an amine group where it reacts with Boc group to protect one of the amine hydrogen and then bound to the bromotetraacetate through the amine group under special reactive conditions, to form the α-8-TPAs N- Ac4riboflavin ligands. This compound can be described as a molecular tweezers in which the flavin moiety acts as a potential electron mediator.

Keywords
REFERENCES
  1. Blackman, A. G. (2005). The coordination chemistry of tripodal tetraamine ligands. Polyhedron, 24(1), 1-39. https://doi.org/10.1016/j.poly.2004.10.012
  2. Caprio, V., & Mann, J. (1998). Synthesis of novel chromeno [3, 4-b] pyridinones. Journal of the Chemical Society, Perkin Transactions 1, (19), 3151-3156. https://doi.org/10.1039/A805650A
  3. Chuang, C. L., Dos Santos, O., Xu, X., & Canary, J. W. (1997). Synthesis and cyclic voltammetry studies of copper complexes of Bromo-and Alkoxyphenyl-substituted derivatives of Tris (2-pyridylmethyl) amine: influence of cation− Alkoxy interactions on copper redox potentials. Inorganic chemistry, 36(9), 1967-1972. https://doi.org/10.1021/ic960942y
  4. Harata, M., Jitsukawa, K., Masuda, H., & Einaga, H. (1995). Synthesis and structure of a new tripodal polypyridine copper (II) complex that enables to recognize a small molecule. Chemistry letters, 24(1), 61-62. https://doi.org/10.1246/cl.1995.61
  5. Machkour, A., Mandon, D., Lachkar, M., & Welter, R. (2004). Easy preparation of the tris (2-fluoro-6-pyridylmethyl) amine ligand and instantaneous reaction of the corresponding dichloroferrous complex with molecular dioxygen: New access to dinuclear species. Inorganic chemistry, 43(4), 1545-1550. https://doi.org/10.1021/ic034485e
  6. Machkour, A., Thallaj, N. K., Benhamou, L., Lachkar, M., & Mandon, D. (2006). The Coordination Chemistry of FeCl3 and FeCl2 to Bis[2-(2,3-dihydroxyphenyl)-6-pyridylmethyl](2-pyridylmethyl)amine: Access to a Diiron(III) Compound with an Unusual Pentagonal-Bipyramidal/Square-Pyramidal Environment. Chemistry–A European Journal, 12(25), 6660-6668. https://doi.org/10.1002/chem.200600276
  7. Malek, Z. S., & Labban, L. M. (2021). Photoperiod regulates the daily profiles of tryptophan hydroxylase-2 gene expression the raphe nuclei of rats. International Journal of Neuroscience, 131(12), 1155-1161. https://doi.org/10.1080/00207454.2020.1782903
  8. Malek, Z. S., Dardente, H., Pevet, P., & Raison, S. (2005). Tissue‐specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles. European Journal of Neuroscience, 22(4), 895-901. https://doi.org/10.1111/j.1460-9568.2005.04264.x
  9. Malek, Z. S., Dardente, H., Pevet, P., & Raison, S. (2005). Tissue‐specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles. European Journal of Neuroscience, 22(4), 895-901. https://doi.org/10.1111/j.1460-9568.2005.04264.x
  10. Malek, Z. S., Pevet, P., & Raison, S. (2004). Circadian change in tryptophan hydroxylase protein levels within the rat intergeniculate leaflets and raphe nuclei. Neuroscience, 125(3), 749-758. https://doi.org/10.1016/j.neuroscience.2004.01.031
  11. Malek, Z. S., Pevet, P., & Raison, S. (2004). Circadian change in tryptophan hydroxylase protein levels within the rat intergeniculate leaflets and raphe nuclei. Neuroscience, 125(3), 749-758. https://doi.org/10.1016/j.neuroscience.2004.01.031
  12. Malek, Z. S., Sage, D., Pévet, P., & Raison, S. (2007). Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity. Endocrinology, 148(11), 5165-5172. https://doi.org/10.1210/en.2007-0526
  13. Malek, Z. S., Sage, D., Pévet, P., & Raison, S. (2007). Daily rhythm of tryptophan hydroxylase-2 messenger ribonucleic acid within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity. Endocrinology, 148(11), 5165-5172. https://doi.org/10.1210/en.2007-0526
  14. Malek, Z., & Labban, L. (2019). A comparative study of tryptophan hydroxylase's circadian rhythm in the functional parts of dorsal raphe nuclei in the mesencephalon. European Journal of Pharmaceutical and Medical Research, 6(11), 527-532.
  15. Mandon, D., Machkour, A., Goetz, S., & Welter, R. (2002). Trigonal bipyramidal geometry and tridentate coordination mode of the tripod in FeCl2 complexes with tris (2-pyridylmethyl) amine derivatives bis-α-substituted with bulky groups. Structures and spectroscopic comparative studies. Inorganic chemistry, 41(21), 5364-5372. https://doi.org/10.1021/ic011104t
  16. Miyaura, N., Yanagi, T., & Suzuki, A. J. S. C. (1981). The palladium-catalyzed cross-coupling reaction of phenylboronic acid with haloarenes in the presence of bases. Synthetic Communications, 11(7), 513-519. https://doi.org/10.1080/00397918108063618
  17. Murray, T. A., & Swenson, R. P. (2003). Mechanism of flavin mononucleotide cofactor binding to the Desulfovibrio vulgaris flavodoxin. 1. Kinetic evidence for cooperative effects associated with the binding of inorganic phosphate and the 5 ‘-phosphate moiety of the cofactor. Biochemistry, 42(8), 2307-2316. https://doi.org/10.1021/bi026967s
  18. Murray, T. A., Foster, M. P., & Swenson, R. P. (2003). Mechanism of flavin mononucleotide cofactor binding to the Desulfovibrio vulgaris flavodoxin. 2. Evidence for cooperative conformational changes involving tryptophan 60 in the interaction between the phosphate-and ring-binding subsites. Biochemistry, 42(8), 2317-2327. https://doi.org/10.1021/bi026968k
  19. Offermann, W., & Vögtle, F. (1980). Brominations with N‐Bromosuccinimide: Solvent and Selectivity. Angewandte Chemie International Edition in English, 19(6), 464-465. https://doi.org/10.1002/anie.198004641
  20. Prévot-Halter, I., Smith, T. J., & Weiss, J. (1997). Assembling organic receptors around transition metal templates: functionalized catechols and dioxomolybdenum (VI) for the recognition of dicarboxylic acids. The Journal of Organic Chemistry, 62(7), 2186-2192. https://doi.org/10.1021/jo960836d
  21. Pueyo, J. J., Curley, P. G., & Mayhew, S. G. (1996). Kinetics and thermodynamics of the binding of riboflavin, riboflavin 5′-phosphate and riboflavin 3′, 5′-bisphosphate by apoflavodoxins. Biochemical journal, 313(3), 855-861. https://doi.org/10.1042/bj3130855
  22. Romary, J. K., Zachariasen, R. D., Barger, J. D., & Schiesser, H. (1968). New 2-pyridyl polyamines. Synthesis, spectra, and proton dissociation constants. Journal of the Chemical Society C: Organic, 2884-2887. https://doi.org/10.1039/J39680002884
  23. Shuman, R. T., Ornstein, P. L., Paschal, J. W., & Gesellchen, P. D. (1990). An improved synthesis of homoproline and derivatives. The Journal of Organic Chemistry, 55(2), 738-741. https://doi.org/10.1021/jo00289a058
  24. Thallaj, N. (2021). Synthesis of a New Ligand Tris (2-pyridylmethyl) amine functionalized by a methoxy group and study of Dichloroferrous complexes, its reactivity to dioxygen both in the presence and absence of substrate. International Journal of Applied Chemical and Biological Sciences, 2(4), 65-77.
  25. Thallaj, N. (2021). Synthesis of a New Ligand Tris (2-pyridylmethyl) amine functionalized by a methoxy group and study of Dichloroferrous complexes, its reactivity to dioxygen both in the presence and absence of substrate. International Journal of Applied Chemical and Biological Sciences, 2(4), 65-77. https://identifier.visnav.in/1.0001/ijacbs-21f-07003/
  26. Thallaj, N. K., Machkour, A., Mandon, D., & Welter, R. (2005). Square pyramidal geometry around the metal and tridentate coordination mode of the tripod in the [6-(3′-cyanophenyl)-2-pyridylmethyl] bis (2-pyridylmethyl) amine FeCl 2 complex: a solid state effect. New Journal of Chemistry, 29(12), 1555-1558. https://doi.org/10.1039/B512108F
  27. Thallaj, N. K., Machkour, A., Mandon, D., & Welter, R. (2005). Square pyramidal geometry around the metal and tridentate coordination mode of the tripod in the [6-(3′-cyanophenyl)-2-pyridylmethyl] bis (2-pyridylmethyl) amine FeCl 2 complex: a solid state effect. New Journal of Chemistry, 29(12), 1555-1558. https://doi.org/10.1039/B512108F
  28. Thallaj, N. K., Mandon, D., & White, K. A. (2007). The design of metal chelates with a biologically related redox-active part: Conjugation of riboflavin to bis (2-pyridylmethyl) amine ligand and preparation of a ferric complex. European journal of inorganic chemistry, (1), 44-47. https://doi.org/10.1002/ejic.200600789
  29. Thallaj, N. K., Mandon, D., & White, K. A. (2007).The design of metal chelates with a biologically related redox-active part: Conjugation of riboflavin to bis (2-pyridylmethyl) amine ligand and preparation of a ferric complex. European journal of inorganic chemistry, (1), 44-47. https://doi.org/10.1002/ejic.200600789
  30. Thallaj, N. K., Orain, P. Y., Thibon, A., Sandroni, M., Welter, R., & Mandon, D. (2014). Steric Congestion at, and Proximity to, a Ferrous Center Leads to Hydration of α-Nitrile Substituents Forming Coordinated Carboxamides. Inorganic chemistry, 53(15), 7824-7836. https://doi.org/10.1021/ic500096h
  31. Thallaj, N. K., Przybilla, J., Welter, R., & Mandon, D. (2008). A ferrous center as reaction site for hydration of a nitrile group into a carboxamide in mild conditions. Journal of the American Chemical Society, 130(8), 2414-2415. https://doi.org/10.1021/ja710560g
  32. Thallaj, N. K., Przybilla, J., Welter, R., & Mandon, D. (2008). A ferrous center as reaction site for hydration of a nitrile group into a carboxamide in mild conditions. Journal of the American Chemical Society, 130(8), 2414-2415. https://doi.org/10.1021/ja710560g
  33. Tyeklar, Z., Jacobson, R. R., Wei, N., Murthy, N. N., Zubieta, J., & Karlin, K. D. (1993). Reversible reaction of dioxygen (and carbon monoxide) with a copper (I) complex. X-ray structures of relevant mononuclear Cu (I) precursor adducts and the trans-(. mu.-1, 2-peroxo) dicopper (II) product. Journal of the American Chemical Society, 115(7), 2677-2689. https://doi.org/10.1021/ja00060a017
  34. Walker, W. H., Singer, T. P., Ghisla, S., & Hemmerich, P. (1972). Studies on Succinate Dehydrogenase: 8α‐Histidyl‐FAD as the Active Center of Succinate Dehydrogenase. European Journal of Biochemistry, 26(2), 279-289. https://doi.org/10.1111/j.1432-1033.1972.tb01766.x
  35. Walsh, M. A., McCarthy, A., O'Farrell, P. A., McArdle, P., Cunningham, P. D., Mayhew, S. G., & Higgins, T. M. (1998). X‐ray crystal structure of the Desulfovibrio vulgaris (Hildenborough) apoflavodoxin‐riboflavin complex. European journal of biochemistry, 258(2), 362-371. https://doi.org/10.1046/j.1432-1327.1998.2580362.x
  36. Wane, A., Thallaj, N. K., & Mandon, D. (2009). Biomimetic Interaction between FeII and O2: Effect of the Second Coordination Sphere on O2 Binding to FeII Complexes: Evidence of Coordination at the Metal Centre by a Dissociative Mechanism in the Formation of μ‐Oxo Diferric Complexes. Chemistry–A European Journal, 15(40), 10593-10602. https://doi.org/10.1002/chem.200901350
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