Biomimicking molecules coordinated to Ruthenium centre
The main aspect of my current research is concerninng the design of new organometallic complexes, based on Ru coordinated bioactive species.
In the past 10 years, it has been commonly assumed that Ruthenium species replaced as anticancer compound the most popular and commonly used cis-Platinum drug for more effectiveness.
Infact they reveal two main advantageous requisites:
-surmounting the resistance upon longer treatments, that generally affect the common Pt drugs used generally in the case of severe and drastic conditions.
-and limiting the toxic effects towards the intact cells.
With this respect it warrants to underline that base-research investigations on the coordination structures exhibited by newly synthesized Ru-complexes are certainly of primary interest to correlate the structure modulation to the sometimes
inexplicable, multifaceted anticancer activity. Firstly, I’m going to make a premise showing the previous reactions that we studied by applying the strategy of coordinating nucleobases as thymine to the Ru-metal site as an effective approach to promptly obtain novel bioactive molecules. In our case we use a thymine opportunely derivatized by a carboxy tethered function. The choice is founded to the reason that carboxy moiety is shown by a great number of biological metals to effectively graph the enzymes. In our case the synthesis with two equivalents of THAcH (tymine acetic acid) revealed a particularly sustainable path because the product formation releases molecular hydrogen only, and affords a doubly coordinated complex exhibiting simultaneously a chelate and monohapto-thymine acetates. On the contrary In the case of 1 equivalent a large metallacycle has instead been obtained showing an heteroleptic, namely mixed (N,O) coordination. It is opportune to underpin that metal skeleton rigidity and steric encumbrance both drive the reactions prevalently towards O-coordination, unless the impeded rotation of one coordinate thymine-acetate about the large phosphine ligands is removed by the cleavage of one Ru-P bond followed by reposition in mutual (vicinal)
cis-location. It is remarkable to note that because of the reduced acidity exhibited by the metal center, the addition of a second ligand is consistently more difficult and commonly requires longer times and higher temperature- solicitated reactions. So, in line with these considerations, in the second attach monoacetate-coordination together with
trans-cis isomerization predominates for steric reasons. What it is important to know is that metal anchoring promotes a process called
tautomerization which implies reposition of the proton atoms towards new isomeric forms, that can be a key-point for interpreting the biological activity, such as cell apoptosis, because of the mismatching in pairing the tween-nucleobase belonging to the DNA. Likewise, in the case of pyrrolyl-carboxy acid ligand, exclusively (O,O) coordinative fashion mode is obtained, in which an equatorial position prevails, parallelly at least to one phenyl Phosphine substituent. The Density Functonal Theory-calculations suggest the identification of planar stereogeometry for all the possible stable molecular model structures (that means that all exhibit the lower energy as possible), suggesting the occurrence of remarkable intramolecular interactions between the almost parallel aromatic rings such as p-p stacking and also between the acidic pyrrole NH-functions with the p-cloud of the same phenyl phosphines. Another relevant interaction is shown on the other side of the molecule by the -CH (irbidized sp
2) of the phenyl substituents almost perpendicular with the carbonyl-Ru fragment. All together these short-range intramolecular interactions evaluated by comparison with the sum of Van der Waals radii) are globally 18, and are responsible to determine the most stable thermodynamic structures. It is worthy to recall that the Infrared shifts of Ru-carbonyl frequency may be considered as a probe for the reaction trend and the diastereomers are defined by the reciprocal location of Ru-H and Ru-CO functions. On the other hand, the hydride NMR resonances, designated by very high-shifted signals are a convincing evidence of the number of the isomeric species obtained. New perspectives imply the adoption of immuno-modulator ligands as asparagine or 5-HTP 5-hydroxytriptophane molecule as serotonin promoter, to study the benign synergistic effects of the natural molecules with the stabilizing action of Ru metal site viewed as carrier center and mediator towards the living fragments as DNA. Many chemical features, as stability and solubility in very polar media (by simulating the plasma liquid mainly composed by water), should be furtherly studied to achieve a potential response towards anticancer activity. Many biological answers as are still claimed by in-vitro and in-vivo trials towards specific tumoral cellular lines. Long way is prospecting to achieve an auspicable pharmaceutical drug remedy… but any plausible single path is worthy to be under-stepped, to not leave unattended any novel strategies to cope and solve the common enemy for the entire living population.
