New examples of expanded hetero 2,6‐pyrihexaphyrins 2–6 were synthesized in 12–18 % yields by condensing one equivalent of [10,10'‐bis(p‐tert‐butylphenyl)hydroxymethyl]‐1,3‐bis(2‐thienyl)‐pyridine diol with five different tripyrranes, under mild acid catalyzed conditions. The formation of 2,6‐pyrihexaphyrins 2–6 was confirmed by corresponding molecular ion peak in HR‐MS and were thoroughly characterized by 1D and 2D NMR spectroscopy, absorption, electrochemical and DFT/TD‐DFT studies. In 1H NMR, the proton resonances were either upfield or downfield shifted as the nature of one of the core heterocycles was varied from pyrrole to furan, thiophene, selenophene, and tellurophene indicating that the electronic properties of the macrocycle were altered by changing the core heterocycle. The NMR studies indicated that the macrocycles were nonaromatic in nature and absorption spectra of 2,6‐pyrihexaphyrins 2–6 showed one broad absorption band in the region of 600–1000 nm and two relatively sharp bands in the region of 350–500 nm. The aza analogue 2 showed considerable red shift in the absorption bands compared to other hetero 2,6‐pyrihexaphyrins 3–6. Upon protonation of the macrocycles, the resulting protonated macrocycles 2.H22+‐6.H22+ exhibits bathochromically shifted absorption bands. The redox studies indicated that the 2,6‐pyrihexaphyrins 2–6 are electron deficient and DFT studies supported the distortion and nonaromatic nature of the macrocycles.

New examples of nonaromatic fused expanded porphyrins containing both pyridine and crown ether moiety as a part of macrocyclic framework were synthesized by condensing pyridine based pentapyrrane with polyether‐based diol in CH2Cl2 in the presence of one equivalent of BF3 ⋅ OEt2 under inert conditions followed by oxidation with DDQ in open air. The condensation was expected to form pyridine‐containing crowned expanded porphyrins but resulted in the formation of fused crowned expanded porphyrins due to intramolecular fusion of two pyrrole nitrogens with two adjacent inverted thiophene carbons as revealed by X‐ray crystallography obtained for one of the macrocycle. HRMS and NMR studies supported the formation of fused crowned pyridine containing expanded porphyrins, and the macrocycles showed simple, well‐resolved NMR spectra where all resonances were identified easily by 2D NMR spectroscopy. The macrocycles exhibited typical nonaromatic absorption features and showed one broad band with peak maxima at 535 nm and one or two shoulder bands in the higher energy region. The protonation studies resulted in clear colour change from purple to blue and absorption bands experienced bathochromic shifts with a broad band at 662 nm which was extended up to 800 nm. The electrochemical studies revealed that the macrocycles were easier to oxidize but difficult to reduce. DFT studies indicated that the macrocycle attains a very puckered and distorted ‘U’ shaped structure owing to the flexibility of the crown ether chain and TD‐DFT studies corroborated experimental results. The preliminary studies indicated that the macrocycles could be used as colorimetric optical sensor for the detection of Cu2+ ion.

Objective: The main aim of this study was to formulate, develop and optimized a duloxetine hydrochloride (dlx-hcl) loaded mucoadhesive microemulsion intended for intranasal administration. Methods:Established on solubility studies capmul mcm, transcutol-p, labrasol were used as oil, co-surfactant and surfactant respectively. The optimized mucoadhesive microemulsion prepared using water titration method was further characterized for particle size, polydispersity index, zeta potential and conductivity measurements followed by drug content, nasal cilio toxicity and biochemical estimation of the selected formulation.Results: All physicochemical parameters conducted, proved that dlx-hcl microemulsion was appropriate for nasal delivery. Chitosan, used as mucoadhesive polymer demonstrated enhanced retention time of the microemulsion in nasal mucosa with no signs of toxicity and epithelial damage. The particle size and zeta potential were found to be of 200 nm and-15 mV respectively considering the formulation safe for nasal delivery. Conclusion:This formulation strategy can be used as an effective targeting technique for the drugs having low bioavailability and poor brain penetration along with an effective method for the treatment long-term disease like depression.

Two examples of nonaromatic m-benziheptaphyrins and two examples of aromatic p-benziheptaphyrins were synthesized by [5 + 2] condensation of appropriate m-benzi pentapyrrane and p-benzi pentapyrrane respectively and bithiophene diol in CH 2 Cl 2 in the presence of one equivalent of TFA under inert conditions for 30 min followed by oxidation with DDQ in open air for 1 h. The 1 H NMR studies carried out at room temperature as well as at lower temperature indicated the nonaromatic nature of m-benziheptaphyrins with inversion of two thiophene rings and aromatic nature of p-benziheptaphyrins with inversion of one of the thiophene ring. The X-ray structure obtained for one of the p-benziheptaphyrins showed a planar conformation with alignment of one of the thiophene ring away from the macrocyclic inner core but maintained its coplanarity with the mean plane and supported the aromatic nature of the macrocycle. The absorption spectra of m-benziheptaphyrins resembled with the nonaromatic systems and showed two intense bands at 445 nm, 555 nm and a very broad band in the region of 600-1100 nm whereas the pbenziheptaphyrin showed three sharp intense bands at 534 nm, 585 nm and 832 nm due to their aromatic nature. The protonation of m-benziheptaphyrins and p-benziheptaphyrins resulted in significant bathochromic shifts in their absorption maxima and showed strong absorption in NIR region. The electrochemical studies indicated that m-& pbenziheptaphyrins undergo oxidations and reductions easily. DFT and TD-DFT studies were in agreement with the experimental observations.

We report here one of the rare examples of expanded hexaphyrins named as dithia pyribenzihexaphyrin macrocycles containing six-membered rings such as pyridine and p-phenylene along with five-membered heterocycles such as pyrrole and thiophene as a part of a macrocyclic frame. Trifluoroacetic acid catalyzed [3 + 3] condensation of equimolar mixture of [10,10′bis(p-tert-butyl phenyl)hydroxymethyl]-1,3-bis(2-thienyl)pyridine diol (2,6-pyri diol) and 1,4-bis(phenyl(1H-pyrrol-2-yl)methyl)benzene (p-benzidipyrrane) in CH 2 Cl 2 followed by oxidation with DDQ afforded stable nonaromatic dithia 2,6-pyri-para-benzihexapyrins 1 and 2 in 6−8% yields. The macrocycles were characterized by high-resolution mass spectroscopy and 1D and 2D NMR spectroscopy. NMR studies revealed the nonaromatic nature of dithia 2,6-pyri-p-benzihexaphyrins and indicated that the para-phenylene ring prefers to be in quininoid form rather than in benzenoid form. The macrocycles displayed sharp absorption bands in the region of ∼380−500 nm and a broad band at ∼700 nm, reflecting their nonaromatic nature. Upon protonation, these macrocycles showed NIR absorption properties. The redox studies of macrocycles indicated their electron-deficient nature. The DFT/TD-DFT studies are in line with the experimental observations.