Reactivity, photolability, and computational studies of the ruthenium nitrosyl complex with a substituted cyclam fac-[Ru(NO)Cl2(κ3N4,N8,N11(1-carboxypropyl)cyclam)]Cl·H2O

Abstract

Chemical reactivity, photolability, and computational studies of the ruthenium nitrosyl complex with a substituted cyclam, fac-[Ru(NO)Cl(2)(κ(3)N(4),N(8),N(11)(1-carboxypropyl)cyclam)]Cl·H(2)O ((1-carboxypropyl)cyclam = 3-(1,4,8,11-tetraazacyclotetradecan-1-yl)propionic acid)), (I) are described. Chloride ligands do not undergo aquation reactions (at 25 °C, pH 3). The rate of nitric oxide (NO) dissociation (k(obs-NO)) upon reduction of I is 2.8 s(-1) at 25 ± 1 °C (in 0.5 mol L(-1) HCl), which is close to the highest value found for related complexes. The uncoordinated carboxyl of I has a pK(a) of ∼3.3, which is close to that of the carboxyl of the non coordinated (1-carboxypropyl)cyclam (pK(a) = 3.4). Two additional pK(a) values were found for I at ∼8.0 and ∼11.5. Upon electrochemical reduction or under irradiation with light (λ(irr) = 350 or 520 nm; pH 7.4), I releases NO in aqueous solution. The cyclam ring N bound to the carboxypropyl group is not coordinated, resulting in a fac configuration that affects the properties and chemical reactivities of I, especially as NO donor, compared with analogous trans complexes. Among the computational models tested, the B3LYP/ECP28MDF, cc-pVDZ resulted in smaller errors for the geometry of I. The computational data helped clarify the experimental acid-base equilibria and indicated the most favourable site for the second deprotonation, which follows that of the carboxyl group. Furthermore, it showed that by changing the pH it is possible to modulate the electron density of I with deprotonation. The calculated NO bond length and the Ru/NO charge ratio indicated that the predominant canonical structure is [Ru(III)NO], but the Ru-NO bond angles and bond index (b.i.) values were less clear; the angles suggested that [Ru(II)NO(+)] could contribute to the electronic structure of I and b.i. values indicated a contribution from [Ru(IV)NO(-)]. Considering that some experimental data are consistent with a [Ru(II)NO(+)] description, while others are in agreement with [Ru(III)NO], the best description for I would be a linear combination of the three canonical forms, with a higher weight for [Ru(II)NO(+)] and [Ru(III)NO].

The nature of Ru–NO bonds in ruthenium tetraazamacrocycle nitrosyl complexes—a computational study

“…This strategy has been explored using mono-N-substituted cyclam with carboxyor amino-propyl groups. [56][57][58] It should be stressed that controlling the properties of the complex, such as electronic spectra, reduction potential, and specific rate constant of the release of NO, is crucial for biological applications. [15][16][17][18][19][20][21][22][23]37,38,[59][60][61][62][63] Tetraazamacrocycles such as cyclam and its derivatives are fairly flexible; they adopt five different configurations, depending on the spatial alignment of the NH protons (Fig.…”

The versatile ruthenium(II/III) tetraazamacrocycle complexes and their nitrosyl derivatives

“…It is well understood that electrochemical data are important not only to characterize but also to understand and predict the reactivities of complexes, as is the case of Ru III/II redox potentials of macrocyclic complexes [21,22,24,25,[32][33][34][35][36]47,[68][69][70]79,[147][148][149]. These values are reasonably close to those of analogous complexes with non-cyclic amines [24,34,148], and are dependent on ring size, increasing slightly as the macrocyclic cavity increases, as can be seen for the [14]aneN4, [15]aneN4, and [16]aneN4 trans-dichlorido complexes whose values are −150, −125, and −95 mV vs NHE, respectively (Table 4).…”

“…4) [43,44]. Ruthenium nitrosyl complexes exhibit favorable properties for biological application as NO delivery agents, such as solubility in water, induced release of NO by chemical, electrochemical or photochemical means, and also thermal stability; notably they do not decompose for years [5,33,34,39,43,[45][46][47]. They also proved to have biological activity .…”

“…Both the chemical properties and biological activities of ruthenium nitrosyl complexes have been extensively investigated [40,[48][49][50][51], not only in solution but also incorporated into drug delivery systems such as polymeric nanoparticles [52][53][54]. With that aim, a large number of ruthenium nitrosyl complexes with macrocyclic ligands ([Ru(NO)L(mac)] q+ ) have been reported [40,47,48,50].…”

Computational study of ruthenium-nitrosyl compounds

“…93,94 We also studied these compounds by using the all-electron scalar relativistic treatment with the Douglas-Kroll-Hess of second order (DKH2); we also employed B3LYP and full electron def2-TZVP, 95 to Ru-NO 2 ) originated from increases in pH. 37 We used the B3LYP/cc-pVDZ 97,98 computational model along with ECP28MDF for ruthenium. 99 We used the Gaussian 09 rev.…”