BAZI YENİ İLAÇ ÖNCÜSÜ BENZOTİYAZOLİNON TÜREVLERİ ÜZERİNE ÇOK DEĞİŞKENLİ SAR ÇALIŞMALARI

Yeni modellenen analjezik aktif otuziki benzotiyazolinon türevinin çok değişkenli yapı-aktivite ilişkileri iki farklı kemometric metot olan temel bileşen analizi (PCA) ve hiyerarşik kümeleme analizi (HCA) kullanılarak incelendi. Moleküllerin elektronik, termokimyasal ve hidrofobik özelliklerini tanımlayan yirmi moleküler tanımlayıcı Austin Modeli (AM1) ve yoğunluk fonksiyonel teorisi (DFT) kullanılarak hesaplandı. HCA ve PCA metotları sıvı fazdaki (HOFSıvı) polarizebilite (α), elektrofilik indis (ω) ve oluşum ısısı ile uygulanır. Sonuçlar otuziki molekülü aktifve inaktif olarak iki grupta sınıflandırmak için oldukça etkili bulundu. Korelasyon matrisi ve değişken ağırlığı moleküllerin hesaplanan fizikokimyasal parametreleri arasındaki ilişkileri açıklamak için kullanıldı. İncelenen bileşiklerin ana halkasına F ve OCH3 sübstitüentlerin eklenmesi ve piperazin üzerindeki alkil gurubunun uzaması biyolojik aktiviteyi değiştir

UV-Induced Benzyloxy Rotamerization in an Ortho OH-Substituted Aryl Schiff Base

A new benzyloxy containing ortho hydroxyl-substituted aryl Schiff base, trans 2-((2-(benzyloxy)benzylidene) amino)phenol (abbreviated as BBAP), was synthesized and characterized by 1H-, 13C-NMR and infrared spectroscopic techniques and elemental analysis. The conformational landscape of the compound, as well as its infrared spectra in argon and N2 cryogenic matrices (10 K) were investigated, followed by the study of the effects of in situ UV irradiation of the matrix-isolated compound. The structural information was obtained through an extensive series of quantum chemical calculations performed at the DFT(B3LYP)/6-311++G(d,p) level of theory, which enabled to identify 3 low-energy OH···N intramolecularly H-bonded conformers of the molecule that were later found to be present in the as-deposited cryogenic matrices. The 3 experimentally relevant conformers of BBAP differ in the geometry of the benzyloxy substituent, and were discovered to interconvert upon in situ UV irradiation (λ = 230 nm) of the matrix-isolated compound. This is the first report on UV-induced conformational changes taking place in a benzyloxy fragment for a matrix-isolated compound

Structural Relevance of Intramolecular H-Bonding in Ortho-Hydroxyaryl Schiff Bases: The Case of 3-(5-bromo-2-hydroxybenzylideneamino) Phenol

A new Schiff base compound, 3-(5-bromo-2-hydroxybenzylideneamino)phenol (abbreviated as BHAP) was synthesized and characterized by 1H- and 13C- nuclear magnetic resonance and infrared spectroscopies. DFT/B3LYP/6-311++G(d,p) calculations were undertaken in order to explore the conformational space of both the E- and Z- geometrical isomers of the enol-imine and keto-amine tautomers of the compound. Optimized geometries and relative energies were obtained, and it was shown that the most stable species is the E-enol-imine form, which may exist in four low-energy intramolecularly hydrogen-bonded forms (I, II, V, and VI) that are almost isoenergetic. These conformers were concluded to exist in the gas phase equilibrium with nearly equal populations. On the other hand, the infrared spectra of the compound isolated in a cryogenic argon matrix (10 K) are compatible with the presence in the matrix of only two of these conformers (conformers II and V), while conformers I and VI convert to these ones by quantum mechanical tunneling through the barrier associated with the rotation of the OH phenolic group around the C-O bond. The matrix isolation infrared spectrum was then assigned and interpreted with help of the DFT(B3LYP)/6-311++G(d,p) calculated infrared spectra for conformers II and V. In addition, natural bond orbital (NBO) analysis was performed on the most stable conformer of the experimentally relevant isomeric form (E-enol-imino conformer V) to shed light on details of its electronic structure. This investigation stresses the fundamental structural relevance of the O-H···N intramolecular H-bond in o-hydroxyaryl Schiff base compounds