¹⁹F magnetic resonance imaging (MRI) is a promising tool in medical diagnostics. An important class of ¹⁹F MRI contrast agents is based on paramagnetic resonance enhancement. This effect allows an improvement in sensitivity by increasing the number of scans per unit of time or facilitates the development of responsive contrast agents that are based on changes in relaxation rates as a detection principle. In this work, Bloch-Redfield-Wangsness relaxation theory was used to predict the relaxation properties of existing lanthanoid and transition metal complexes of fluoroorganic ligands and to evaluate several design strategies for responsive contrast agents. Electron-nucleus dipole-dipole, Curie relaxation, and contact interactions were included in the model. Potential significance of chemical shift anisotropy-anisotropic dipolar shielding cross-correlation was discussed. The calculated and experimental results were well aligned. The presented model, along with the optimized field-dependent values of electronic relaxation times, could be used for the preliminary selection of the optimal metal ion for applications in ¹⁹F MRI. The results indicate potential advantages of other metal ions in addition to Gd³⁺ particularly Cu²⁺, Mn²⁺, Ni²⁺, Fe³⁺, and other lanthanoids as a part of ¹⁹F contrast agents.

Oligonucleotides with the sequences 5′-GTG AU^PA TGC, 5′-GCA TAU^P CAC and 5′-GU^PG ATA U^PGC, where U^P is 2′-O-propargyl uridine, were subjected to post-synthetic Cu(I)-catalyzed azide–alkyne cycloaddition to attach 1,4,7,10-tetraazacyclododecane (cyclen) and two well-known DNA intercalating dyes: thioxanthone and 1,8-naphthalimide. We propose a convenient cyclen protection–deprotection strategy that allows efficient separation of the resulting polyamine–oligonucleotide conjugates from the starting materials by RP-HPLC to obtain high-purity products. In this paper, we present hitherto unknown macrocyclic polyamine–oligonucleotide conjugates and their hybridization properties reflected in the thermal stability of thirty-two DNA duplexes containing combinations of labeled strands, their unmodified complementary strands, and strands with single base pair mismatches. Circular dichroism measurements showed that the B-conformation is retained for all dsDNAs consisting of unmodified and modified oligonucleotides. An additive and destabilizing effect of cyclen moieties attached to dsDNAs was observed. T_m measurements indicate that placing the hydrophobic dye opposite to the cyclen moiety can reduce its destabilizing effect and increase the thermal stability of the duplex. Interestingly, the cyclen-modified U showed significant selectivity for TT mismatch, which resulted in stabilization of the duplex. We conclude the paper with a brief review and discussion in which we compare our results with several examples of oligonucleotides labeled with polyamines at internal strand positions known in the literature.