A controlled NO-releasing compound: synthesis, molecular structure, spectroscopy, electrochemistry, and chemical reactivity of R,R,S,S-trans-[RuCl(NO)(cyclam)]2+(1,4,8,11-tetraazacyclotetradecane).
The synthesis of trans-[RuCl(NO)(cyclam)]2+ (cyclam = 1,4,8,11-tetraazacyclotetradecane) can be accomplished by either the addition of cyclam to K2[RuCl5NO] or by the addition of NO to trans-[RuCl(CF3SO3)(cyclam)](CF3-SO3). Crystals of trans-[RuCl(NO)(cyclam)](ClO4)2 form in the monoclinic space group P2(1)/c, with unit cell parameters of a = 7.66500(2) A, b = 24.7244(1) A, c = 16.2871(2) A, beta = 95.2550(10) degrees, and Z = 4. One of the two independent molecules in the unit cell lies disordered on a center of symmetry. For the ion in the general position, the Ru-N and N-O bond distances and the [Ru-N-O]3+ bond angle are 1.747(4) A, 1.128(5) A, 178.0(4) degrees, respectively. In both ions, cyclam adopts the (R,R,S,S) configuration, which is also consistent with 2D COSY 1H NMR studies in aqueous solution. Reduction (E degree = -0.1 V) results in the rapid loss of Cl- by first-order kinetics with k = 1.5 s-1 and the slower loss of NO (k = 6.10 x 10(-4) s-1, delta H++ = 15.3 kcal mol-1, delta S++ = -21.8 cal mol-1 K-1). The slow release of NO following reduction causes trans-[RuCl(NO)(cyclam)]2+ to be a promising controlled-release NO prodrug for vasodilation and other purposes. Unlike the related complex trans-[Ru(NO)(NH3)4(P(OEt)3)](PF6)2, trans-[RuCl(NO)(cyclam)]Cl2 is inactive in modulating evoked potentials recorded from mice hippocampal slices probably because of the slower dissociation of NO following reduction.
Lang
D R
DR
Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02167, USA.
Davis
J A
JA
Lopes
L G
LG
Ferro
A A
AA
Vasconcellos
L C
LC
Franco
D W
DW
Tfouni
E
E
Wieraszko
A
A
Clarke
M J
MJ
D000818:Animals; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006624:Hippocampus; D007700:Kinetics; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C471988:(RuCl(NO)(cyclam))2; D016166:Free Radical Scavengers; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D011355:Prodrugs; D014665:Vasodilator Agents; C024560:cyclam; D009569:Nitric Oxide