Chemistry of HIV-1 virucidal Pt complexes having neglected bidentate sp2 N-donor carrier ligands with linked triazine and pyridine rings. synthesis, NMR spectral features, structure, and reaction with guanosine.
Complexes of the types LPtCl2 and [L2Pt]X2 [L = substituted 3-(pyridin-2'-yl)-1,2,4-triazine] were synthesized and characterized by NMR spectroscopy and, for the first time, by X-ray crystallography in an effort to determine the coordination properties of this novel class of inorganic medicinal agents possessing HIV-1 virucidal activity. The agents containing either one or two sp2 N-donor bidentate ligands are referred to as ptt (platinum triazine) agents. The X-ray structures of three LPtCl2 compounds revealed the expected pseudo-square-planar geometry. The X-ray structure of [(pyPh2t)2Pt](BF4)2 [pyPh2t = 3-(pyridin-2'-yl)-5,6-diphenyl-1,2,4-triazine] has the expected trans relationship of the unsymmetrical L and is essentially planar, an unusual property for a Pt(II) complex with two bidentate sp2 N donors. HIV-1 is an RNA virus; the guanosine ribonucleoside (Guo) binds (MepyMe2t)PtCl2 at both (inequivalent) available coordination sites to form [(MepyMe2t)Pt(Guo)2]2+ [MepyMe2t = 3-(4'-methylpyridin-2'-yl)-5,6-dimethyl-1,2,4-triazine]. This adduct has four nearly equally intense Guo H8 signals attributed to two pairs of head-to-tail (HT) and head-to-head (HH) conformers, which interchange rapidly within each pair. However, equilibration between pairs requires rotation of the Guo cis to the MepyMe2t pyridyl ring, and the H6' proton on this ring projects toward the Guo and hinders Guo rotation about the Pt-N7 bond. Thus, the HT/HH pairs do not interchange; such behavior is rare. Guo did not add to [(MepyMe2t)2Pt]2+, a result suggesting the possibility that the virucidal activity of LPtCl2 and [L2Pt]2+ ptt agents arises respectively from covalent and noncovalent (possibly intercalative interactions favored by [L2Pt]2+ planarity) binding to biomolecular targets.
Maheshwari
Vidhi
V
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Bhattacharyya
Debadeep
D
Fronczek
Frank R
FR
Marzilli
Patricia A
PA
Marzilli
Luigi G
LG
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D018360:Crystallography, X-Ray; D006151:Guanosine / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry*
D019380:Anti-HIV Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D011725:Pyridines; D014227:Triazines; D006151:Guanosine