Effects of 2,3-dihydrophthalazine-1,4-dion unit on therapeutic properties of organic fluorescent dyes

Kanser, vücudun diğer kısımlarına yayılabilen ve hemen hemen tüm organlarını etkileyebilen bir hastalık grubudur. O nedenle kanser çok ciddi bir sağlık problemi olup tüm dünyada toplumlara sosyal ve ekonomik olarak ağır yükler getirmektedir. Üstelik hali hazırda kullanılan ameliyat, kemoterapi, radyoterapi, immün terapi gibi klinik yöntemlerin birçoğunun etkinliği bu yöntemlere özgü dezavantajlar nedeniyle arzu edilen düzeyde değildir. O nedenle kanser tedavisinde kullanılabilecek etkili yöntem ve ilaçların geliştirilmesi için dünya çapında araştırmalar yapılmaktadır. Araştırmalar özellikle teranostik olarak işlev görebilecek ve kombine tedaviler için elverişli yeni nesil malzemelerin geliştirilmesi üzerine odaklanmıştır. Bu tez çalışmasında kanser tedavisine imkân verecek organik bileşiklerin rasyonel tasarımı sentezi ve karakterizasyonu üzerinde durulmuştur. Tasarımda bir yanda reaktif oksijen türlerine karşı duyarlılık gösterecek bir ünite; diğer yanda ise üstün özellikleri ile biyogörüntüleme, fotodinamik terapi, ve/veya fototermal terapi için elverişli floresans boyaları aynı anda bünyesinde bulunduran yeni bileşikler elde edilmiştir. Sentezlenen floresans malzemelerin yapıları spektroskopik yöntemler ile aydınlatılmış ve fotoduyarlaştırıcı ajanlar olarak potansiyelleri belirlenmiştir. Elde edilen veriler, burada tasarlanan yapıların teranostik ajan olarak işlev görebileceğini ve kombine tedaviler için elverişli yeni nesil malzemeler olarak kullanılabileceğini göstermektedir.Cancer is a group of diseases that can spread to other parts of the body and affect almost all organs. Therefore, it is a very serious health problem and brings heavy social and economic burdens to societies all over the world. Moreover, the effectiveness of many of the current clinical methods, such as surgery, chemotherapy, radiotherapy, and immune therapy, are not at the desired level due to the specific disadvantages of each method. Consequently, enormous effort has been devoted to develop effective methods and drugs that can be used in cancer treatment worldwide. In particular, research has focused on the development of next-generation materials that can function as theranostics and are suitable for combinatorial therapies. In this thesis, rational design, synthesis and characterization of organic compounds that will enable cancer treatment are described. The design was rationalized by combination of two distinct units. The first unit is sensitive to reactive oxygen species whereas the second one consists of fluorescent organic dyes which are suitable for bioimaging, photodynamic therapy, and/or photothermal therapy with their superior properties. The structures of the synthesized fluorescent materials were elucidated by spectroscopic methods and their potential as photosensitizers was determined. The obtained data show that the designed structures can function as theranostic agents and can be used as new generation materials suitable for combinatorial therapies

N/O Dönor atomlu siklofosfazen bileşiklerinin sentezi ve sterokimyasal özelliklerinin incelenmesi

Tez (Yüksek Lisans) -- Kırıkkale Üniversitesi86908

The synthesis of N/O donor type cyclophosphazene compounds and investigation of their steregenic properties

YÖK Tez ID: 343313Bu çalışmada, salisilaldehit ile t-bütilamin ve anilinin etkileştirilmesinden imin bileşikleri, bu bileşiklerin NaBH4 ile indirgenmesinden N-alkil/aril-o-hidroksibenzilamin bileşikleri [1, 2] sentezlendi. N-alkil/aril-o-hidroksibenzilamin bileşiklerinin trimer (N3P3Cl6) ile 1:1 mol oranında THF çözücüsü içerisinde etkileştirilmesinden monospiro-fosfazen türevleri [3, 4] sentezlendi. Monospiro-fosfazen bileşikleri ile pirolidin, morfolin ve 1,3-diaminopropanın reaksiyonlarından [5-16] bileşikleri sentezlendi.Sentezlenen bileşiklerin yapıları elemental analiz, MS, FT-IR, 1H-, 13C-, 31P-NMR teknikleri verilerinden faydalanılarak aydınlatıldı. Tek kristalleri elde edilen bileşik [4]'ün kristal yapıları X-ışınları kristallografi yöntemi ile aydınlatıldı. Ayrıca bileşiklerin stereojenik özellikleri [5-8] CSA ilaveli 31P-NMR çalışmaları ile belirlendi.Anahtar Kelimeler: Fosfor-azot bileşikleri, Spiro-siklofosfazen, AminofosfazenIn these study, N-alkyl/aril-o-hydroxybenzylamines [1, 2] have been obtained by the reduction of corresponding imines which prepared by the reactions of t-butylamine and aniline with 2-hydroxybenzaldehyde in alcohol solution, with NaBH4. The monospiroscyclophosphazene derivatives [3, 4] have been obtained from the reactions of 1 equiv. Of N3P3Cl6 (trimer) with 1 equiv. N-substituded-o-hydroxbenzylamines in THF solutions. The reactions of compounds have been obtaned the reaction of monospirocyclotriphosphazenes with pyrrolidine, morpholine and 1,3-diaminopropane [5-16].The structure of the compounds have been elucidated by elemental analyses, MS, FT-IR, 1H-, 13C-, 31P-NMR techniques. The crystal structure of [4] is determined by X-ray crystallography. The stereogenic properties of compounds [5-8] are confirmed by 31P-NMR spectroscopy on addition of the chiral solvating agent (CSA).Key Words: Phosphorus-nitrogen compounds, Spiro-cyclophosphazene, Aminophosphazen

2-(4-Methyl­Pyridin-2-Yl)-4′,4′,6′,6′-Tetra­Kis­(Pyrrolidin-1-Yl)-1H,2H-Spiro­[Naphtho­[1,2-E][1,3,2]Oxaza­Phosphinine-3,2′-[1,3,5,2,4,6]Tri­Aza­Triphosphinine]

In the title spiro-phosphazene derivative, C33H46N9OP3, the phosphazene and six-membered N/O rings are in flattened chair and twisted-boat conformations, respectively. The naphthalene ring system and the pyridine ring are oriented at a dihedral angle of 41.82 (4)°. In the crystal, weak C—H⋯O hydrogen bonds link the mol­ecules related by translation along the a axis into chains. C—H⋯π inter­actions aggregate these chains into layers parallel to the ab plane.PubMedScopu

A comparison of quantitative parameters of axial posture and spinal mobility between motor subtypes of Parkinson’s disease

Background and purpose – Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder characterized by contradictory clinical outcomes among its several subtypes. The disease can manifest with a tremor-dominant (TD) or a non-tremordominant (NTD) phenotype. Although the TD subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of axial symptoms. For this reason, in this study it was aimed to make a quantitative comparison of axial posture and spinal mobility between PD with TD and NTD. Methods – This case-control study was conducted on 94 patients with diagnosed PD. A group diagnosis approach was used in the study, such that the diagnosis of each patient was confirmed, and they were assigned to TD and NTD groups by a neurologist expert on movement disorders. Of the patients with PD, 61 were in the TD group, and 33 were in the NTD group. Spinal mouse was used to measure spinal posture and spinal mobility in both sagittal and frontal planes. Results – Two groups of 61 patients (25 male + 36 female) with TD-PD (mean age:\ud 64.49±10.37 years) and 33 patients (20 male +13 female) with NTD-PD (mean age: 63.45±9.11 years) were enrolled in the study. There were no significant differences between the patients with TD and NTD in terms of sagittal and frontal postures (p>0.05). In addition to this, anterior trunk tilt was found to significantly increase as the disease stage advanced in both groups. While the greatest anterior trunk tilt change in the TD-PD group was observed in the 3rd stage, NTD-PD group was in the 2.5th stage. Aside from this, the outcomes of the spinal mobility measurements in the frontal and sagittal planes were similar between the groups (p>0.05). Conclusion – It is widely acknowledged that many clinical aspects of the TD and NTD forms of PD differ; however, in our study, it was observed that there may be no difference in the axial symptoms of the patients with PD in terms of classification according to tremor dominance

Aza-BODIPY based fluorescent and colorimetric sensors and probes

Aza-boron-dipyrromethenes (Aza-BODIPYs) represent an important class of chromophores absorbing and emitting in the near-infrared (NIR) region. They have unique optical and electronic features and higher physiological and photo stability than other NIR dyes. Especially after the development of facile synthetic routes, Aza-BODIPYs have become indispensable fluors that can find various applications ranging from chemosensors, bioimaging, phototherapy, solar energy materials, photocatalysis, photon upconversion, lasers, and optoelectronics. Herein, we review Aza-BODIPY based fluorescent and colorimetric chemosensors. We show the potential and untapped toolbox of Aza-BODIPY based fluorescent and colorimetric chemosensors. Hence, we divide the fluorescent and colorimetric chemosensors and probes into five sections according to the target analytes. The first section begins with the chemosensors developed for pH. Next, we discuss Aza-BODIPY based ion sensors including, metal ions and anions. Finally, we present the chemosensors and probes concerning reactive oxygen (ROS) and nitrogen species (RNS) along with biologically relevant species in the last two sections. We believe that Aza-BODIPYs are still in their infancy, and they have a promising future for translation from the bench to real biomedical and materials science applications. After two decades of intensive research, it seems that there are many more to come in this already fertile field. Overall, we hope that future work will further expand the applications of Aza-BODIPY in many areas

BODIPY and 2,3-Dihydrophthalazine-1,4-Dione Conjugates As Heavy Atom-Free Chemiluminogenic Photosensitizers

We disclose an interesting concept for developing heavy atom-free chemiluminogenic photosensitizers. To accomplish this, conjugates 2 and 3, which are composed of boron-dipyrromethene (BODIPY) and 2,3-dihydrophthalazine-1,4-dione units, are investigated. 2 and 3 are compared in terms of their photophysical properties, chemiluminescence responses, and singlet oxygen production. Strikingly, the results indicate that decoration of BODIPY with the 2,3-dihydrophthalazine-1,4-dione scaffold boosts the singlet oxygen generation. Furthermore, treatment of epidermoid laryngeal carcinoma Hep-2 (Hep-2) cells with conjugates 2 and 3 results in efficient cellular internalization which ensures live- cell imaging of Hep-2 cells. Finally, it is noteworthy that in vitro cytotoxicity assays reveal that both 2 and 3 induce cytotoxicity when illuminated with red light. Thus, 2 and 3 represent heavy atom-free chemiluminogenic photosensitizers

BODIPY and 2,3-dihydrophthalazine-1,4-dione conjugates as heavy atom-free chemiluminogenic photosensitizers

We disclose an interesting concept for developing heavy atom-free chemiluminogenic photosensitizers. To accomplish this, conjugates 2 and 3, which are composed of boron-dipyrromethene (BODIPY) and 2,3-dihydrophthalazine-1,4-dione units, are investigated. 2 and 3 are compared in terms of their photophysical properties, chemiluminescence responses, and singlet oxygen production. Strikingly, the results indicate that decoration of BODIPY with the 2,3-dihydrophthalazine-1,4-dione scaffold boosts the singlet oxygen generation. Furthermore, treatment of epidermoid laryngeal carcinoma Hep-2 (Hep-2) cells with conjugates 2 and 3 results in efficient cellular internalization which ensures live- cell imaging of Hep-2 cells. Finally, it is noteworthy that in vitro cytotoxicity assays reveal that both 2 and 3 induce cytotoxicity when illuminated with red light. Thus, 2 and 3 represent heavy atom-free chemiluminogenic photosensitizers

Structural and computational characterization of 4 ',4 ',6 ',6 '-tetrachloro-3-(2-methoxyethyl)-3H,4H-spiro-1,3,2-benzoxaza phosphinine-2,2 '-[1,3,5,2,4,6]triazatriphosphinine

WOS: 000376050700031In this study a new monospirocyclic phosphazene derivative, 4',4',6',6'-tetrachloro-3-(2-methoxyethyl)3H,4H-spiro [1,3,2-benzoxazaphosphinine-2,2'- [1,3,5,2,4,6] triazatriphosphinine] (SP1) was synthesized from the reaction of hexachlorocyclotriphosphazene (N3P3CI6) with N/0 donor-type, 2-{[(2-Metoxyethyl) amino]methylphenol. The structural investigations of the compound were verified by elemental analyses, MS, FFIR, 1H, 13C, 11 --P NMR spectroscopy and the single crystal X-ray diffraction analysis. The structural and spectroscopic data of the molecule in the ground state were calculated by using density functional method (DFT) using 6-311++G (d, p) basis set. The complete assignments of all vibrational modes were performed on the basis of the total energy distributions (TED). Isotropic chemical shifts (31P, 1H and 13C NMR) were calculated using the gauge-invariant atomic orbital (GIAO) method. Theoretical calculations of bond parameters, harmonic vibration frequencies and nuclear magnetic resonance are in good agreement with experimental results. The electrophilic and nucleophilic attack centers in SP1 were predicted with the local softness values (sit, and si) of individual atoms and it is confirmed that P atoms of the PCl2 groups are nucleophilic attack centers.Kirikkale University, Scientific Research Projects Coordination Unit [2012/14]The authors gratefully acknowledge the financial support from the "Kirikkale University, Scientific Research Projects Coordination Unit" (grant No. 2012/14)

N-doped carbon nanomaterials as fluorescent pH and metal ion sensors for imaging

Herein we describe the facile synthesis of new N-doped carbon nanoparticles (CNPs) obtained from 1,10-phenanthroline by the solvothermal method. Characterization of CNPs were carried out with transmission electron microscope (TEM), X-ray photoelectron spectra (XPS), Fourier transform infrared spectra (FTIR), UV–vis absorption spectra, and luminescence spectra. CNPs were pH sensitive and exploited as fluorescent chemosensors and imaging agents for Al(III) and Zn(II) ions in real-life samples. Remarkably, we show that CNPs can be used for the detection of Al(III) and Zn(II) ions in water samples. Accordingly, the results indicate that CNPs are highly effective in detecting Zn(II) content of cosmetic creams. We also demonstrated that the CNPs could be used for in vitro imaging of Al(III) and Zn(II) in Human Larynx Squamous Cell Carcinoma (Hep-2). Finally, Al(III) imaging in Angelica Officinalis root tissue was also achieved successfully. The CNPs are promising as luminescent multianalyte (pH, Al(III) and Zn(II)) sensors