Ather Farooq Khan

Halogen dance reactions—A review

Halogen Dance (HD) reactions are a useful tool for synthetic chemists as they enable access to positions in aromatic and heteroaromatic systems for subsequent functionalization which are often difficult to address by other methods, hence, allowing entry to versatile scaffolds. While the method can be extremely useful, this transformation is often neglected upon designing synthetic sequences. This may be largely attributed to the lack of comprehensive reference works covering the general principles and outlining the versatility and limitations of the technique. The following review tries to present HD reactions in a clear and concise manner in order to convince more chemists of its advantages. It covers the field of HD reactions from their first observation in 1951 until the present. The important contributions leading to the elucidation of the mechanism are briefly outlined followed by a detailed mechanistic section and a discussion of factors which influence HD reactions. Finally, an overview of HD reactions on various carbocyclic and heterocyclic ring systems and its applications in the synthesis of complex compounds is given.

Bioactive behavior of silicon substituted calcium phosphate based bioceramics for bone regeneration.

Bone graft substitutes are widely used for bone regeneration and repair in defect sites resulting from aging, disease, trauma, or accident. With invariably increasing clinical demands, there is an urgent need to produce artificial materials, which are readily available and are capable of fast and guided skeletal repair. Calcium phosphate based bioactive ceramics are extensively utilized in bone regeneration and repair applications. Silicon is often utilized as a substituent or a dopant in these bioceramics, since it significantly enhances the ultimate properties of conventional biomaterials such as surface chemical structure, mechanical strength, bioactivity, biocompatibility, etc. This article presents an overview of the silicon substituted bioceramics, which have emerged as efficient bone replacement and bone regeneration materials. Thus, the role of silicon in enhancing the biological performance and bone forming capabilities of conventional calcium phosphate based bioceramics is identified and reviewed.

Raman Spectroscopy of Natural Bone and Synthetic Apatites

Abstract Raman spectroscopy of natural bones and hydroxyapatites is described. In addition, how Raman spectroscopy has proved crucial in providing baseline data for the modification of synthetic apatite powders that are routinely used now as bone replacement materials is explained. It is important to understand the chemical structural properties of natural bone. Bone consists of two primary components: an inorganic or mineral phase, which is mainly a carbonated form of a nanoscale crystalline calcium phosphate, closely resembling hydroxyapatite, and an organic phase, which is composed largely of type I collagen fibers. Other constituents of bone tissue include water and organic molecules such as glycosaminoglycans, glycoproteins, lipids, and peptides. Ions such as sodium, magnesium, fluoride, and citrate are also present, as well as hydrogenophosphate. Hence, the mineral phase in bone may be characterized essentially as nonstoichiometric substituted apatite. Such a distinction is important in the development of synthetic calcium phosphates for application as skeletal implants. An understanding of bone function and its interfacial relationship to an implant clearly depends on the associated structure and composition. Therefore, it is essential to fully understand the chemical composition of bone, and Raman spectroscopy is an excellent technique for such an analysis.

Novel synthesis of dihydropyrimidines for α-glucosidase inhibition to treat type 2 diabetes: in vitro biological evaluation and in silico docking.

A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against α-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC50 value 112.21±0.97 μM), to show the enzyme - inhibitor interactions.

Production of chitosan PVA PCL hydrogels to bind heparin and induce angiogenesis

ABSTRACT New blood vessel formation is an essential part of wound healing to provide cells with the nutrients and oxygen for their survival. Many nonhealing ulcers fail to heal because of poor blood supply and skin grafts will also fail to take on poorly vascularized wound beds. There is a real need for proangiogenic biomaterials to assist wound healing. In vivo heparin binds proangiogenic growth factors and helps regulate new blood vessel formation, hence heparin containing biomaterials are attractive. To achieve a hydrogel with high heparin binding capacity a composite of chitosan, poly(vinyl alcohol) (PVA) and polycaprolactone (PCL) was produced. Chitosan is a biodegradable natural polymer with great potential for biomedical applications due to its biocompatibility, high charge density and nontoxicity. PVA is biocompatible and nontoxic with good chemical stability, film-forming ability, and high hydrophilicity. PCL has physicochemical and mechanical properties comparable to those of the biological tissues and due its hydrophilic nature helps in the sustained release of drugs. Accordingly in this study we explored a range of PCL concentrations from 4% to 16% added to hydrogels composed of chitosan and PVA. Heparin was blended into the polymer mixture and the nanoporous structure was created by freeze-drying the PCL hydrogel. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR) and XPS confirmed the presence of sulfur on the surface of the hydrogels. Their porous morphology was investigated by scanning electron microscope (SEM). The Chick Chorionic Allantoic Membrane (CAM) assay was used to study the angiogenic potential of these materials and histology (H&E and Goldner trochome) was used to confirm the presence of new blood vessels inside the hydrogels. We report that the addition of 8% PCL to the hydrogels gave porous structures containing heparin, which significantly increased new blood vessel formation into the hydrogels. These hydrogels offer a new approach to biomaterials, which could be added to wounds to improve vascularization. GRAPHICAL ABSTRACT

Chitosan/hydroxyapatite (HA)/hydroxypropylmethyl cellulose (HPMC) spongy scaffolds-synthesis and evaluation as potential alveolar bone substitutes

Alveolar bone loss is associated with infections and its augmentation is a pre-requisite for the success of dental implants. In present study, we aim to develop and evaluate novel freeze dried doxycycline loaded chitosan (CS)/hydroxyapatite (HA) spongy scaffolds where hydroxypropylmethyl cellulose (HPMC) was added as a crosslinker. Scaffolds displayed compressive strength of 14MPa/cm3 and 0.34 as elastic response. The interconnected pore diameter was 41-273μm, favorably provided the template supporting cells and transport. An overall 10% degradation was seen after 14days studies at pH 7.4 in PBS. Doxycycline hyclate, a frequently used drug to counter oral infections, demonstrated an initial burst release (6-8h), followed by a sustain release profile for the remaining 64h. CS/HA/HPMC scaffolds were nontoxic and promoted pre-osteoblast cell viability as seen with live/dead calcein staining after 24h where scaffolds with 10% and 25% HPMC by weight of scaffold had more viable cells. Scaffolds with 10%, 20% and 25% HPMC by weight of scaffold showed efficient cellular adhesion as seen in scanning electron microscopy images (day 8) indicating that pre-osteoblast cells were able to adhere well on the surface and into the porous structure via cytoplasmic extensions. Hoechst 33258 nuclear staining at day 2 and 8 indicated cell proliferation which was further supported byMTT assay at day 2, 4 and 8. Although all scaffolds supported pre-osteoblast cell viability, alkaline phosphatase (ALP) staining demonstrated that upon induction, differentiation was pronounced in case of scaffolds with 10% HMPC scaffolds. Conclusively, these materials having all the required mechanical and biological properties are potential candidates for alveolar bone regeneration.

Biological behavior of bioactive glasses and their composites

Bioactive glasses (BGs) as third generation biomaterials have the ability to form an interfacial bonding more rapidly than other bioceramics between implant and host tissues in defect treatment. Therefore, BGs have shown great applications in the field of bone tissue engineering, dental materials, skin and other tissue regeneration. This review is based on inorganic and organic BG composites being used in bone tissue engineering and summarizes current developments in improving the biological behavior of BGs and their composites. A main focus was given to highlight the role of BGs and their composites in osteogenic differentiation and angiogenesis, followed by their cytotoxicity, protein adsorption ability and antibacterial properties. BGs were found to enhance the cell proliferation and cell attachment without any toxic effects with a significant increase in metabolic activity and possess osteogenic properties. Organic and inorganic dopants have been used to improve their cytocompatibility, osteoconductivity and promote stem cell differentiation towards the osteogenic lineage. BGs have also been used as graft materials because of their significant role in angiogenesis, as they stimulate relevant cells (i.e. fibroblasts, osteoblasts and endothelial cells) to release angiogenic growth factors. They show good protein adsorption because they act as templates for the adsorption of proteins which in turn depends upon surface properties. Antibacterial effects were also observed in BGs as a result of the high aqueous pH value in body fluids due to the presence of alkaline ions. There has been significant research work performed on silica-based bioactive glasses but not much literature can be found on phosphate- and borate-based bioactive glasses, which have good solubility and degradation, respectively.

Effect of calcium hydroxide on mechanical strength and biological properties of bioactive glass.

In this manuscript for the first time calcium hydroxide (Ca(OH)2) has been used for preparation of bioactive glass (BG-2) by co-precipitation method and compared with glass prepared using calcium nitrate tetrahydrate Ca(NO3)2·4H2O (BG-1), which is a conventional source of calcium. The new source positively affected physical, biological and mechanical properties of BG-2. The glasses were characterized by Fourier transform infrared (FTIR), X-Ray Diffractometer (XRD), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis/Differential Scanning Calorimetry (TGA-DSC), BET surface area analysis and Knoop hardness. The results showed that BG-2 possessed relatively larger surface properties (100m(2)g(-1) surface area) as compared to BG-1 (78m(2)g(-1)), spherical morphology and crystalline phases (wollastonite and apatite) after sintering at lower than conventional temperature. These properties contribute critical role in both mechanical and biological properties of glasses. The Knoop hardness measurements revealed that BG-2 possessed much better hardness (0.43±0.06GPa at 680°C and 2.16±0.46GPa at 980°C) than BG-1 (0.24±0.01 at 680°C and 0.57±0.07GPA at 980°C) under same conditions. Alamar blue Assay and confocal microscopy revealed that BG-2 exhibited better attachment and proliferation of MG63 cells. Based on the improved biological properties of BG-2 as a consequent of novel calcium source selection, BG-2 is proposed as a bioactive ceramic for hard tissue repair and regeneration applications.

Temperature-Responsive Hierarchical Polymer Brushes Switching from Bactericidal to Cell Repellency

Unlike conventional poly(N-isopropylacrylamide) (PNIPAM)-based surfaces switching from bactericidal activity to bacterial repellency upon decreasing temperature, we developed a hierarchical polymer architecture, which could maintain bactericidal activities at room temperature while presenting bacterial repellency at physiological temperature. In this architecture, a thermoresponsive bactericidal upper layer consisting of PNIPAM-based copolymer and vancomycin (Van) moieties was built on an antifouling poly(sulfobetaine methacrylate) (PSBMA) bottom layer via sequential surface-initiated photoiniferter-mediated polymerization. At room temperature below the lower critical solution temperature (LCST), the PNIPAM-based upper layer was stretchable, facilitating contact killing of bacteria by Van. At physiological temperature (above the LCST), the PNIPAM-based layer collapsed, thus leading to the burial of Van and exposure of bottom PSBMA brushes, finally displaying notable performances in bacterial inhibition, dead bacteria detachment, and biocompatibility, simultaneously. Our strategy provides a novel pathway in the rational design of temperature-sensitive switchable surfaces, which shows great advantages in the real-world infection-resistant applications.

N-(2,4,6-Trimethyl-phen-yl)-1,3-thia-zol-2-amine.

In the title compound, C12H14N2S, the dihedral angle between the 1,3,5-trimethylbenzene and 1,3-thiazol-2-amine groups is 73.15 (4)°. In the crystal, inversion dimers linked by pairs of N—H⋯N hydrogen bonds generate R 2 2(8) loops.