Modulation of DNA binding by reversible metal-controlled molecular reorganizations of scorpiand-like ligands

DNA interaction with scorpiand azamacrocycles has been achieved through modulation of their binding affinities. Studies performed with different experimental techniques provided evidence that pH or metal-driven molecular reorganizations of these ligands regulate their ability to interact with calf thymus DNA (ctDNA) through an intercalative mode. Interestingly enough, metal-driven molecular reorganizations serve to increase or decrease the biological activities of these compounds significantly.     

Studies on the interaction of phosphate anions with N-functionalised polyaza[n]paracyclophanes: the role of N-methylation

The synthesis and interaction of N,N',N',N'-tetramethyl-2,6,9,13-tetraaza[14]paracyclophanes (B323Me(4)) with nucleotides and inorganic phosphates is described. An easy methodology is used to define thermodynamic selectivity. The interaction of B323Me4 and ATP has been monitored by (1)H, (31)P NMR and by molecular mechanics, ruling out the possibility of the participation of pi-stacking interactions. Results show that N-methylation is accompanied by a strong increase in the interaction of the resulting macrocycle with ATP.     

Potentiometric,NMR, and Fluorescence‐Emission Studies on the Binding of Adenosine 5′‐Triphosphate (ATP) by Open‐Chain Polyamine Receptors Containing Naphthylmethyl and/or Anthrylmethyl Groups

The interaction in aqueous solution of adenosine 5′‐triphosphate (ATP) with a series of open‐chain polyamines linked at one or both ends to anthrylmethyl or naphthylmethyl fragments was followed by potentiometric titration, ¹H‐, ¹³C‐, and ³¹P‐NMR spectroscopy, and by steady‐state fluorescence measurements. The results revealed greater stabilities for the compounds containing one anthracene moiety than for those with one naphthalene moiety, the stabilities of the compounds with both ends N‐substituted with naphthylmethyl groups being close to those containing just one anthrylmethyl unit. The ¹H‐NMR spectra showed that in all systems, there is involvement of π‐π stacking interactions in the stabilization of the adduct species. The competitive effect of the anions afforded by the supporting electrolyte was checked in some of the studied systems working at two different ionic strenghts (0.15M and 1.0M NaCl). The joint analysis of the spectrofluorimetric titrations and pH‐metric species‐distribution curves showed that for all the ATP? receptor systems, a quenching of the fluorescence occurred upon protonation of the adenine N(1)atom. Steady‐state fluorescence and time‐correlated single‐photon‐counting analysis of a system made up of ATP and a bis‐chromophoric polyamine receptor containing anthracene and naphthalene fluorophores established that the energy‐transfer process between the naphthalene and anthracene moieties is still operative despite the presence of ATP.     

Surface-enhanced Raman study of the interactions between tripodal cationic polyamines and polynucleotides

Raman and surface-enhanced Raman spectra of new DNA/RNA-binding compounds consisting of three imidazole (Im) and three pyridine (Py) rings connected by tripodal polyaminomethylene linkages were obtained by the near-infrared excitation at 1064 nm. Study of interactions of Im and Py polyamines with single-stranded RNA polynucleotides (poly?A, poly?G, poly?C, poly?U), double-stranded DNA polynucleotides (poly?dAdT-poly?dAdT, poly?dGdC-poly?dGdC) and calf thymus DNA (ct-DNA) by surface-enhanced Raman spectroscopy (SERS) reveals unambiguous enhancement of the Raman scattering from the small molecules as well as appearance of new bands in spectra associated mainly with nucleobases. The SERS experiments point toward comparable interactions of Im and Py polyamines with single-stranded purine and pyrimidine polynucleotides. Furthermore, SERS experiments with double stranded polynucleotides reveal the base-pair dependent selectivity of Im and Py, whereby interactions within both, major and minor groove are indicated for poly?dAdT-poly?dAdT, at variance to preferred binding of Im and Py to only major groove of poly?dGdC-poly?dGdC. SERS spectra of Im and Py with ct-DNA imply that protonated amino groups of these compounds preferentially interact with N7 atoms (adenine, guanine) while nitrogen in aromatic rings of polyamines might be attracted to C6-NH(2) (adenine), all sites being located at the major groove of the DNA helix. Wavenumber downshift of the imidazole (Im) and pyridine (Py) ring vibrations supports aromatic stacking interactions of imidazole and pyridine aromatic moieties with DNA base-pairs.     

Luminol Chemiluminescence Reports Photodynamic Therapy‐Generated Neutrophil Activity In Vivo and Serves as a Biomarker of Therapeutic Efficacy

Inflammatory cells, most especially neutrophils, can be a necessary component of the antitumor activity occurring after administration of photodynamic therapy. Generation of neutrophil responses has been suggested to be particularly important in instances when the delivered photodynamic therapy (PDT) dose is insufficient. In these cases, the release of neutrophil granules and engagement of antitumor immunity may play an important role in eliminating residual disease. Herein, we utilize in vivo imaging of luminol chemiluminescence to noninvasively monitor neutrophil activation after PDT administration. Studies were performed in the AB12 murine model of mesothelioma, treated with Photofrin‐PDT. Luminol‐generated chemiluminescence increased transiently 1 h after PDT, followed by a subsequent decrease at 4 h after PDT. The production of luminol signal was not associated with the influx of Ly6G⁺ cells, but was related to oxidative burst, as an indicator of neutrophil function. Most importantly, greater levels of luminol chemiluminescence 1 h after PDT were prognostic of a complete response at 90 days after PDT. Taken together, this research supports an important role for early activity by Ly6G⁺ cells in the generation of long‐term PDT responses in mesothelioma, and it points to luminol chemiluminescence as a potentially useful approach for preclinical monitoring of neutrophil activation by PDT.     

Polyamine Linear Chains Bearing Two Identical Terminal Aromatic Units. Evidence for a Photo Induced Bending Movement

Abstract

Several chemosensors bearing a fluorescent unit at both ends of a linear polyamine chain were synthesised. The protonation as well as the association constants with Cu²⁺ and Zn²⁺ were determined by potentiometry in 0.15 mol dm^?3 NaCl at 298.1 K. In the case of 1,16-bis(1-naphthylmethyl)-1,4,7,10,13,16-hexaazadecane hexahydrochloride (L1), formation of an excimer emission in aqueous acidic solutions was observed. The system was characterized by steady state fluorescence emission and by time resolved fluorescence. In the ground state the molecule is expected to adopt a more or less linear conformation, while in the excited state a bending movement of the chain must occur in order to allow the excimer emission. The system can be viewed as an elementary machine driven by light.     

Thermometric study of the dissociation equilibria of the maleinimidodioxime

The values of the dissociation constants of the maleinimidodioxime are potentiometrically determined at various ionic strengths, and extrapolated to zero ionic strength (pK ₁ ^T =10.41;pk ₂ ^T =11.60). From these values and from the thermometric titration curves the enthalpies of neutralization (H _N1=–21.76,H _N2=–23.77 kJ/mol) and the thermodynamic parameters of dissociation of this substance at 25.0 °C are determined ( G ₁ =59.41, G ₂ =66.23, H ₁ =34.06, H ₂ =32.05 kJ/mol; S ₁ =–85.06, S ₂ =–114.64 J/(K mol)).

---

Zusammenfassung Die Werte der Dissoziationskonstanten von Maleinimidodioxim wurden potentiometrisch bei verschiedenen Ionenstärken bestimmt und auf die Ionenstärke Null extrapoliert (pK ₁ ^T =10.41;pK ₂ ^T =11.60). Aus diesen Werten und aus den thermometrischen Titrierungskurven wurden die Neutralisierungsenthalpien (H _N1=–21.76,H _N2=–23.77 kJ/mol) und die thermodynamischen Dissoziationsparameter dieser Substanz bei 25 °C bestimmt ( G ₁ =59.41, G ₂ = 66.23, H ₁ =34.06 kJ/mol, H ₂ = 32.05 kJ/mol; S ₁ =–85.06, S ₂ =–114.64 J/Kmol.

---

( ₁ =10.41 ₂ =11.60) . H _N1=–21.76 H _N2=–23.77 / 25.0°:G ₁ ⁰ =59.41;G ₂ ⁰ =66.23.H ₁ ⁰ =34.06₂ H ₂ ⁰ = 32.05 /,S ₁ ⁰ =–85.06;S ₂ ⁰ =–114.64 /.