Silvia Biagini

Exploring the Binding Ability of Phenanthroline-Based Polyammonium Receptors for Anions: Hints for Design of Selective Chemosensors for Nucleotides

The synthesis of receptor 2,6,10,14,18-pentaaza[20]-21,34-phenanthrolinophane (L1), containing a pentaamine chain linking the 2,9 positions of a phenanthroline unit, is reported. The protonation features of L1 and of receptor 2,6,10,14,18,22-hexaaza[23]-24,37-phenanthrolinophane (L2) have been studied by means of potentiometric, (1)H NMR, and spectrofluorimetric measurements; this study points out that the fluorescent emission of both receptors depends on the protonation state of the polyamine chain. In fact, the receptors are emissive only at neutral or acidic pH values, where all the aliphatic amine groups are protonated. Potentiometric titrations show that L2 is able to bind selectively ATP over TTP, CTP, and GTP. This selectivity is lost in the case of L1. (1)H and (31)P NMR measurements and molecular mechanics calculations show that the phosphate chains of nucleotides give strong electrostatic and hydrogen-bonding interactions with the ammonium groups of the protonated receptors, while the nucleobases interact either via pi-stacking with phenanthroline or via hydrogen bonding with the ammonium groups. Of note, MM calculations suggest that all nucleotides interact in an inclusive fashion. In fact, in all adducts the phosphate chain is enclosed within the receptor cavities. This structural feature is confirmed by the crystal structure of the [(H(6)L2)(2)(TTP)(2)(H(2)O)(2)](4+) adduct. Fluorescence emission measurements at different pH values show that L2 is also able to ratiometrically sense ATP in a narrow pH range, thanks to emission quenching due to a photoinduced electron transfer (PET) process from an amine group of the receptor to the excited phenanthroline.

Ultrasound discloses entheseal involvement in inactive and low active inflammatory bowel disease without clinical signs and symptoms of spondyloarthropathy

OBJECTIVE To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables. METHODS A total of 81 IBD patients [55 Crohns disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls. RESULTS Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability). CONCLUSIONS US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

Interaction of Mixed-Donor Macrocycles Containing the 1,10-Phenanthroline Subunit with Selected Transition and Post-Transition Metal Ions : Metal Ion Recognition in Competitive Liquid-Liquid Solvent Extraction of CuII, ZnII, PbII, CdII, AgI, and HgII

Two new mixed aza-thia crowns 5-aza-2,8-dithia[9]-(2,9)-1,10-phenanthrolinophane (L(4)) and 2,8-diaza-5-thia[9]-(2,9)-1,10-phenanthrolinophane (L(7)) have been synthesized and characterized. The coordination behavior of L(4) and L(7) toward the metal ions Cu(II), Zn(II), Pb(II), Cd(II), Hg(II), and Ag(I) was studied in aqueous solution by potentiometric methods, in CD3CN/D2O 4:1 (v/v) by (1)H NMR titrations and in the solid state. The data obtained were compared with those available for the coordination behavior toward the same metal ions of structurally analogous mixed donor macrocyclic ligands L(1)-L(3), L(5), L(6): all these contain a phenanthroline subunit but have only S/O/N(aromatic) donor groups in the remaining portion of the ring and are, therefore, less water-soluble than L(4) and L(7). The complexes [Cd(NO3)2(L(5))], [Pb(L(7))](ClO4)2 x 1/2MeCN, [Pb(L(4))](ClO4)2 x MeCN, and [Cu(L(7))](ClO4)2 x 3/2MeNO2 were characterized by X-ray crystallography. The efficacy of L(1)-L(7) in competitive liquid-liquid metal ion extraction of Cu(II), Zn(II), Cd(II), Pb(II), Ag(I), and Hg(II) was assessed. In the absence of Hg(II), a clear extraction selectivity for Ag(I) was observed in all systems investigated.

ATP Recognition and sensing with a phenanthroline-containing polyammonium receptor

A new polyammonium receptor is able to selectively recognise and sense ATP among triphosphate nucleotides, thanks to ATP-induced quantitative quenching of its fluorescence emission.

DNA binding of a proflavine derivative bearing a platinum hanging residue

New platinum(II) complex of 3,6-diamine-9-[6,6-bis(2-aminohethyl)-1,6-diaminohexyl]acridine, AzaPt, has been synthesised and characterised. Behaviour of AzaPt in solution (protonation and possible self-aggregation phenomena) has been investigated by spectral methods (absorbance and fluorescence) at I=0.1M and 25°C, and the equilibrium parameters of binding to calf thymus DNA have been established. Two different modes of DNA binding by the complex were detected, which depend on the polymer to dye molar ratio (P/D). At relatively low P/D values the mode was interpreted as binding by the polyamine residue external to the base pairs, while at high P/D values the binding corresponds to intercalation of the proflavine residue. Such interpretation is supported by the observed salt effect on binding and the temperature variation of the binding constants, which allowed estimating the ΔH and ΔS values contributions. Spectrophotometric analysis of the long time range binding revealed that AzaPt is involved in a slow reaction, interpreted as an attack by the platinum ion on the nucleobases. The time constant for such interaction was calculated and found to be the same order of magnitude as for processes responsible for the action of anti-tumour drugs that do covalently bind to polynucleotides.

FRI0448 Radiological occult sacroiliac abnormalities in asymptomatic patients with inflammatory bowel disease (IBD) might precede the development of spondyloartropathy

Background The involvement of sacroiliac joints (SIJ) is one of the major features of Spondyloartropathies (SpA) associated to inflammatory bowel disease (IBD) and it is well known that the early detection of SIJ inflammation is crucial to identify and treat SpA on-time. Objectives To investigate X rays sacroiliitis in IBD patients, not presenting signs and symptoms of Spondyloarthropathy (SpA), and the differences of IBD clinical and familial variables between patients with sacroiliac (SIJ) abnormalities and without. To follow up sacroiliitis patients during 3 years, evaluating the onset of SpA inflammatory back pain (IBP). Methods 81 patients (55 Crohn-CD- and 26 Ulcerative rettocolitis -UC) with remittent and low active IBD, froma tertiary referral centre of gastroenterology Unit, were studied with X rays of SIJ (postero-anterior and oblique scan) and scored with the New York criteria by two rheumatologists. Differences of IBD clinical variables (CD and UC, remittent and low active bowel disease, durations of symptoms, extra-intestinal involvement, patients treated with surgery and not, ESR and CRP) and familiarity (for psoriasis, IBD, celiac syndrome, SpA), between patients with SIJ X rays findings and without were investigated. At three years of follow up, we re-evaluated patients with radiological sacroiliitis for onset of chronic (>3 months) IBP, belong Berlin definition, and, finally, for ASAS criteria positivity. Results 22/81 patients (27,1%) showed X rays sacroiilitis at baseline. New York grade 1 and 2 was observed in 17/22 (77,3%) and 12/22 (54,5%) patients, respectively. X rays sacroiliac involvement did not correlate with IBD clinical and familial variables. All patients were HLA B27 negative. After 3 years of clinical evaluation, 6/22, presented episodic IBP, 1/22 presented only back morning stiffness >30 minutes (>3 months) without pain and 3/22 developed chronic (> 3 months consecutive of duration) with almost two Berlin criteria for IBP. The three patients fulfilling Berlin criteria for chronic IBP, showing SIJ bone oedema at MRI (either with gadolinium either with STIR), underwent to ASAS definition for Spa and met the indication for antiTNF alpha treatment (never assumed before for IBD). Conclusions In IBD, occult X rays sacroiliitis in IBD might precede the onset of axial symptoms. At the moment, none clinical feature at baseline might be indentified to define those patients at risk to develop SpA. Disclosure of Interest None Declared