Excited Charge Separation in a π-Interacting Phenothiazine-Zinc Porphyrin-Fullerene Donor-Acceptor Conjugate.

We have designed, synthesized, and characterized a donor-acceptor triad, SPS-PPY-C60, that consists of a π-interacting phenothiazine-linked porphyrin as a donor and sensitizer and fullerene as an acceptor to seek charge separation upon photoexcitation. The optical absorption spectrum revealed red-shifted Soret and Q-bands of porphyrin due to charge transfer-type interactions involving the two ethynyl bridges carrying electron-rich and electron-poor substituents. The redox properties suggested that the phenothiazine-porphyrin part of the molecule is easier to oxidize and the fullerene part is easier to reduce. DFT calculations supported the redox properties wherein the electron density of the highest molecular orbital (HOMO) was distributed over the donor phenothiazine-porphyrin entity while the lowest unoccupied molecular orbital (LUMO) was distributed over the fullerene acceptor. TD-DFT studies suggested the involvement of both the S2 and S1 states in the charge transfer process. The steady-state emission spectrum, when excited either at porphyrin Soret or visible band absorption maxima, revealed quenched emission both in nonpolar and polar solvents, suggesting the occurrence of excited state events. Finally, femtosecond transient absorption spectral studies were performed to witness the charge separation by utilizing solvents of different polarities. The transient data was further analyzed by GloTarAn by fitting the data with appropriate models to describe photochemical events. From this, the average lifetime of the charge-separated state calculated was found to be 169 ps in benzonitrile, 319 ps in dichlorobenzene, 1.7 ns in toluene for Soret band excitation, and ∼320 ps for Q-band excitation in benzonitrile.

Butterfly architecture of NIR Aza-BODIPY small molecules decorated with phenothiazine or phenoxazine.

This is the first report on the highest efficiency NIR absorbing Aza-Bodipy small molecules. The molecular engineering of newly synthesized NIR absorbing Aza-Bodipy dyes consists of covalently linked phenothiazine (AZA-PTZ-BOD) and phenoxazine (AZA-POZ-BOD) moieties as terminal groups and Aza-Bodipy as a central core moiety. The highest efficiency for OPV devices of 8.23% is achieved for AZA-PTZ-BOD.

Hepcidin and Ferritin: Important Mediators in Inflammation Associated Anemia in Systemic Lupus Erythematosus Patients.

Systemic Lupus Erythematosus is an autoimmune disease with female preponderance. Anemia is found in 50% of Systemic Lupus Erythematosus patients. This is a cross sectional case control study with 30 female Systemic Lupus Erythematosus patients having inflammation associated anemia (Hemoglobin < 10.0 gm/dl) and 30 age matched controls with the aim to measure serum hepcidin and ferritin levels, correlate and study their role as homeostatic regulators of iron metabolism and utility as markers. Serum transferrin, ferritin, iron, total iron binding capacity, hsCRP, liver enzymes and renal parameters were analyzed by using automated analyser. Hepcidin levels were estimated by Sandwich-ELISA method. There was significant decrease in Iron (p < 0.0001), Iron Binding capacity (p < 0.0001), Transferrin (p < 0.0001) in patients, and a significant increase in inflammatory markers: hs-CRP (p < 0.0001), ESR (p < 0.0001) compared to controls. Significant increase in both Hepcidin (p < 0.0001) and Ferritin (p < 0.0001) was observed in patients with significant positive correlation (r = 0.711) with each other. Additionally, ferritin and hepcidin significantly positively correlated with hs-CRP and ESR (r = 0.526, 0.735); (r = 0.427, 0.742) respectively. Negative correlation with hemoglobin, iron, total iron binding capacity and transferrin with hepcidin (r = - 0.80, - 0.307, - 0.553, - 0.584) and ferritin (r = -0.722, - 0.22, - 0.654, - 0.728) was observed respectively. On ROC analysis both hepcidin and ferritin has sensitivity of 96.7%, specificity of 100% at cut-off values of 110 and 49 respectively. AUC of hepcidin was 0.993 and ferritin was 0.978. We have established a positive linear correlation between Hepcidin and Ferritin levels in disease activity and the changes correlated with the inflammatory state and anemia in patients, making them important mediators and potential markers of inflammation associated anemia.

Spectrum of monoclonal gammapathies in Andhra Pradesh.

In the present study, monoclonal gammapathy was identified in a total of 245 patients of plasma cell dyscrasias during period of 1987 to 2000. The monoclonal band was identified in serum by agar gel electrophoresis in all the cases and in urine in a few cases. Characterization of paraprotein (monoclonal immunoglobulin class and light chain type) was carried out by employing immunoelectrophoresis and/or immunofixation electrophoresis using heavy chain specific gamma, alpha, mu, delta and epsilon and light chain specific kappa (K), lambda (λ) antisera. Serum immunoglobulins Ig G, Ig A, and Ig M were estimated by immunoturbidometry. Serum urea, creatinine, uric acid, alkaline phosphatase, total proteins, albumin, calcium and phosphorus were estimated by using routine biochemical methods. Among the 245 cases, 73.1% monoclonal gammapathies were of secretory type and 7.3% were non-secretory. Monoclonal gammapathies were associated with 80.4% of multiple myeloma, 8.9% of solitary plasmacytoma, 4.1% of extra-medullary plasmacytoma, 3.3% of lymphoma and 2.9% of plasma cell leukemia. Classification of secretory monoclonal immunoglobulin revealed monoclonal immunoglobulin Ig G in 74%, Ig A 15% and Ig M in 2.9% cases.

Application of tumor markers in ovarian malignancies.

Ovarian cancer is the fifth leading cause of death in women. The incidence of this malignancy increases in women over the age of 40. The overall five years survival is less than 30%, as most women present with advanced stage disease. Until recently, detection of early stage ovarian cancer has been difficult since it is usually nonpalpable and asymptomatic. The definitive diagnosis of an ovarian mass is a common problem in gynecologic patients with adnexal mass. The routine standard evaluation for adnexal masses includes patient's history, physical examination, ultrasound and histopathological examination. These parameters individually or in combination have little predictive value. The accuracy of diagnostic tools are of immense value and great concern to practicsing Gynecologists and Oncologists. The clinical application of serum concentration of CA 125, AFP and hCG is of great help not only as diagnostic aid but also in monitoring efficacy of any treatment modality like chemotherapy, radiotherapy or surgical resection. Additionally, evaluation of tumor marker concentration helps in predicting early biochemical recurrence and in prognostication in different types of ovarian malignancies. The ability to differentiate a malignant mass from a benign pelvic mass pretherapeutically could be enhanced optimally by additional use of tumor markers such as cancer antigen CA-125, alphafetoprotein and human chorionic gonadotrophin in pre-and postmenopausal women.

Sequence specific molecular recognition and binding by a GC recognizing Hoechst 33258 analogue to the decadeoxyribonucleotide d-[CATGGCCATG]2: structural and dynamic aspects deduced from high field 1H-NMR studies.

The non-exchangeable and imino proton NMR resonances have been assigned of the 1:1 complex of an analogue 2 of Hoechst 33258 1 bound to the decadeoxyribonuycleotide d-[CATGGCCATG]2 by a combination of NOE difference, COSY and NOESYPH techniques. In contrast to Hoechst 33258 which recognizes 5'-AATT sequences exclusively, analogue 2 possesses structural features designed to permit the recognition of GC sites. The NOESY and 1D-NOE experiments place the drug in the minor groove and it is located on the 5'-CCAT sequence. The orientation of the drug in the groove is such as to place the N-methylpiperazine terminus at a GC site. Cross-correlation peaks in the NOESY experiment show that the DNA duplex retains its right-handed B form, similar to that in the free decamer. Specific NOEs locate the benzoxazole moiety on the 5'-CCAT and are consistent with the pyridine nitrogen forming a new hydrogen bond to G(4)-2NH2 at 5'-CCAT. The drug appears to undergo rotation around the C9-C10 bond, at a rate comparable with NMR time scale, even after binding. Variable temperature 1H-NMR studies established that the DNA is thermally stabilized as a result of the drug binding. The drug binding is a dynamic process involving exchange between the equivalent 5'-CCAT sites at approximately 60s-1 with delta G degree of 65 kJ mol-1 at 308K. The experimental evidence is in accord with a slide-swing mechanism for this process.

Molecular recognition and binding of a GC site-avoiding thiazole-lexitropsin to the decadeoxyribonucleotide d-[CGCAATTGCG]2: 1H-NMR evidence for thiazole intercalation.

The structural and dynamic aspects of the interaction of the thiazole containing lexitropsin (1) with an oligodeoxyribonucleotide were studied by high field 1H-NMR spectroscopy. Complete assignment of the 1H-NMR resonances of lexitropsin 1 was accomplished by 2D-NMR techniques. The complexation-induced chemical shifts and NOE cross peaks in the NOESY map of the 1:1 complex of lexitropsin (1) and d-[CGCAATTGCG]2 reveal that the thiazole ring of the lexitropsin (1) intercalates between dA4.A5 bases and the rest of the ligand resides in the minor groove of the AT rich core of decamer, thus occupying the 5'-AATT sequence on the DNA. Intercalation of the thiazole moiety of the drug has been detected by the presence of intermolecular NOEs both in the major and the minor groove of the decamer helix. The absence of intranucleotide NOEs between base protons and H1'/H2' protons suggested local unwinding of the binding site on the DNA. From COSY and NOESY methods of 2D-NMR, it was established that the N-formyl (amino) terminus of the thiazole lexitropsin (1) is projecting into the major groove towards A5H8 while the amidinium terminus lies in the minor groove towards the T7G8 base pairs of the opposite strand. The expected intranucleotide NOEs confirmed that the decadeoxyribonucleotide in the 1:1 complex exists in a right handed B-conformation. The presence of exchange signals along the binding site 5'-AATT indicated an exchange of the bound drug process wherein the rate of exchange between the two equivalent sites was estimated to be congruent to 130 s-1 at 30 degrees C and with delta G degrees of 62.4 kJ mol-1. Force field and Pi calculations permitted a rationalization of the experimentally observed binding mode in terms of preferred conformation of the ligand and repeat length in lexitropsins compared with the DNA receptor.

Molecular recognition between oligopeptides and nucleic acids: DNA sequence specificity and binding properties of thiazole-lexitropsins incorporating the concepts of base site acceptance and avoidance.

The DNA binding and sequence specificity of a group of six novel thiazole containing lexitropsins related to the natural anti-tumor antibiotic distamycin have been examined by complementary strand MPE footprinting on two restriction fragments of pBR322 DNA. These lexitropsins comprise two groups in which the hetero atom of the thiazole moiety directed inwards to the floor of the minor groove is respectively nitrogen or sulfur. All of the new lexitropsins bind to DNAs in the minor groove with Kapp comparable with distamycin. The group of lexitropsins bearing nitrogen directed towards the DNA display comparable binding to poly(dA-dT) and to native DNAs, and complementary strand footprinting reveals their ability to accept and bind to mixed AT-GC sequences. The GC recognizing property plausibly arises from the hydrogen bonding between the thiazole nitrogen and G-2-NH2 based on precedents. In contrast the group of lexitropsins bearing sulfur directed towards the floor of the minor groove of DNA exhibit strict preference for AT sequences and are even more discriminating than distamycin. The latter agents, in common with the first group, bind firmly in the minor groove and with a binding site size of either 4 +/- 1 or 5 +/- 1 base pairs indicating intimate contact of all parts of the ligand. Therefore the property of GC site avoidance of these particular thiazole-lexitropsins is attributed to clash between the sterically more demanding sulfur and G-2NH2 groups.