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)

Abstract

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.

Chemical and photochemical properties of a ruthenium nitrosyl complex with the N-monosubstituted cyclam 1-(3-Propylammonium)-1,4,8,11-tetraazacyclotetradecane

“…The structure of this complex in solution is shown in Figure 3 2 (κ 3 N 4 ,N 8 ,N 11 (1-carboxypropyl)cyclam)] + , a very closely related cyclam monosubstituted complex, where the cyclam ring N (with the carboxypropyl pendant arm instead of an aminopropyl) is not coordinated to the ruthenium, resulting in κ 3 denticity. 19 Figures S3 and S4) is similar to those of other ruthenium nitrosyl complexes, 17,18,25 especially that of the related cyclam complex, trans-[Ru(NO) Cl(cyclam)] 3+ , as expected. This is due to the similarity of the ligands and, therefore, the bands were assigned by analogy.…”

“…The structure of this complex in solution is shown in Figure 3, and is similar to those of trans- [Ru(NO) Figures S3 and S4) is similar to those of other ruthenium nitrosyl complexes, 17,18,25 especially that of the related cyclam complex, trans-[Ru(NO) Cl(cyclam)] 3+ , as expected. This is due to the similarity of the ligands and, therefore, the bands were assigned by analogy.…”

“…The ratio of the Ep 1c and Ep 1a current peak heights approaches unity as the scan rate increases, consistent with a coupled chemical reaction, assigned to the slow loss of NO following reduction to trans- [Ru(NO) The cyclic voltammetric behavior of trans-[Ru(NO) Cl(1-pramcyH)](PF 6 ) 3 in 0.1 mol L -1 CF 3 SO 3 H/CF 3 SO 3 Na at pH 1 and 25 ºC is very similar to that of trans-[Ru(NO) Cl(cyclam)] 3+ . 25 At a 100 mV s -1 scan rate, there are three electrochemical processes, namely Ep 1c = -390 mV, Ep 2c = -530 mV, and Ep 2a = -400 mV vs. Ag/AgCl (Figure 4). At these conditions, peak 1a (see ahead) is enveloped by peak 2a; peaks 2c and 2a are pH dependent in the 1-9 pH range, while the others are pH independent.…”

“…18 for comparison, and it has a relatively simple resonance pattern regarding the NH-cyclam hydrogens, as a result of the higher symmetry of the cyclam moiety in this geometry. 25 There are two signals in the 5-7. 59 In its turn, the 13 …”

“…Cl(1-pramcyH)](PF 6 ) 3 in acetonitrile [25º C; 100 mV s -1 ; m = 0.1 mol L -1 tba(PF 6 )] reveals three electrochemical processes in the -1.6 V to + 1 V range (vs. Ag/AgCl): Ep 2c = -1350 mV, Ep 1c = -320 mV and Ep 1a = -220 mV ( Figure S5) 25 At a 100 mV s -1 scan rate, there are three electrochemical processes, namely Ep 1c = -390 mV, Ep 2c = -530 mV, and Ep 2a = -400 mV vs. Ag/AgCl (Figure 4). At these conditions, peak 1a (see ahead) is enveloped by peak 2a; peaks 2c and 2a are pH dependent in the 1-9 pH range, while the others are pH independent.…”