Bimetallic Complexes of Spiro‐Azacrown Ligands as Catalysts of Phosphoester and Phosphoric Anhydride Cleavage

Abstract

The ability of bimetallic homo- and heteronuclear complexes of two spiro-linked ligands, viz. a biazacrown (i.e., 2,6,10,14,18,22-hexaazaspiro[11.11]tricosane (1)) and an azacrown-crown ether (i.e., 14,17,20,23,26-pentaoxa-2,6,10-triaza-spiro[11.15]heptacosane (2)), to promote the cleavage of the phosphoester linkage of dinucleoside 3',5'-phosphates and the phosphoric anhydride bridge of dinucleoside 5',5'-triphosphates was studied. In both reactions, the bimetallic homonuclear Cu2+ and Zn2+ complexes were better catalysts than their monometallic counterparts. The acceleration was two- to five-fold with the phosphoester cleavage and 3- to 20-fold with the phosphoric anhydride cleavage. Interestingly, the most-efficient catalyst of the phosphoester cleavage was the heterodinuclear Ni2+,Zn2+ complex of 1, the catalytic activity of which was up to 5- and 100-fold that of the homodinuclear Zn2+ and Ni2+ complexes, respectively. Moreover, this cooperative acceleration was observed to depend on the identity of the 5'-linked nucleoside: 3',5'-UpU and 3',5'-ApU were cleaved much faster than 3',5'-UpA, and no cooperative acceleration was observed with 3',5'-ApA. The reaction was second-order in hydroxide ion concentration, suggesting that a double deprotonation took place on going from the initial to the transition state. Evidently, in addition to deprotonation of the attacking 2'-OH group, N(3)H of the 5'-linked uridine was displaced by one of the metal ions of the cleaving agent. With the phosphoric anhydride cleavage, no similar cooperativity of two different metal ions was observed, but the greatest rate-acceleration was achieved with the homodinuclear Cu2+ complexes.

Hydrolysis of a mRNA 5′-cap model substrate, 5′,5′-ApppA by di- and trinuclear zinc(II) complexes of a polyamino-polyol ligand

“…The requirements for hydrolysing the phosphodiester bonds of NpNs or polyribonucleotides by metal complexes may, however, partly differ from those for the cleavage of the triphosphate bridge of the cap-structure. Catalysis of the leaving group departure that was found to be inevitable in case of many of our recently studied catalysts [27,40,46] is likely to be of much less importance in cleaving the cap-structure. Consequently, the dinuclear (or trinuclear) metal ion complexes of tmci may be potential candidates for targeting the triphosphate bridge of ApppA.…”

“…According to the reported activities, the Lewis-acidity of the metal ions plays a rather important but certainly not exclusive role in promoting the process. Examples of efficient cleavage by complexes of copper(II) and trivalent lanthanide ions have been reported [26][27][28][29][30][31][32], whereas the catalysis by monomeric zinc(II) complexes is modest [26][27][28]31]. The rate of the cleavage was found to be second-order on the concentration of simple copper(II) complexes [26].…”

“…In another study, the rate acceleration provided by a mononuclear europium(III) complex was significantly enhanced by the presence of zinc(II) ions [32]. Consequently, the catalysis seems to require two metal ions, therefore bimetallic species are generally more efficient catalysts for the cleavage of cap-models than their mononuclear counterparts [24,27,30,31].…”

“…Similarly to the internucleosidic phosphodiester bonds of RNA or RNA model substrates, the hydrolysis of the triphosphate bridge in cap-models can also be enhanced by metal ions and their complexes [24][25][26][27][28][29][30][31][32]. According to the reported activities, the Lewis-acidity of the metal ions plays a rather important but certainly not exclusive role in promoting the process.…”

Structural features of the adenosine conjugate in means of vibrational spectroscopy and DFT

“…Among them, macrocycles having DNA heterocyclic bases as sidearms play a remarkable role as model molecules in designing molecular reagents, carriers or catalysts [1]. Several important efforts have been reported in this field of DNA modification presenting these conjugates as potential fluorescent reporter groups [2,3], catalytic centers [4,5], surface-binding handles, immune response moieties [6], and prodrugs with anti-HIV activity [7]. In addition, these complexes possess metal ions coordination abilities [8].…”