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Dive into the research topics where Khadijah M. Hindi is active.

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Featured researches published by Khadijah M. Hindi.


Chemical Reviews | 2009

The medicinal applications of imidazolium carbene-metal complexes.

Khadijah M. Hindi; Matthew J. Panzner; Claire A. Tessier; Carolyn L. Cannon; Wiley J. Youngs

Ofele and Wanzlick reported the synthesis of the first N-heterocyclic carbene (NHC) metal complexes in 1968.1,2 The isolation of the first free carbene by Arduengo in 1991 set the scene for an ever-growing interest and advancement in the field of N-heterocyclic carbene chemistry.3 Shortly thereafter, the use of these ligands in organometallic chemistry, particularly in catalysis dramatically increased.4,5 N-heterocyclic carbenes are neutral 2-electron donors, with an ability to bond to both hard and soft metals making them more versatile ligands than phosphines.6 As an added advantage, not only are NHCs easier to synthesize and functionalize than phosphines but they also form a stronger bond to metals and therefore form more stable metal complexes than metal phosphine complexes.7,8 The N-heterocyclic carbene ligands interact with metal centers primarily through strong σ-donation and to a lesser degree through π-backdonation (Figure 1).9,10 Figure 1 Orbital diagram of NHC bonding to metal center. Ghosh and coworkers11,12,13,14,15,16 as well as others17,18,19 took special interest in the exceptional stability of several metal-NHC complexes and conducted in depth analyses in order to gain better insights into the structure and bonding. In particular, the metal-ligand donor-acceptor interactions were inspected using the charge decomposition analysis (CDA). CDA is a tool used to quantitatively estimate the degree of NHC → metal σ-donation, designated by d, and NHC ← metal π-back donation, designated by b.20,21 Thus a higher d/b ratio emphasizes the ability of NHC to function as an effective σ-donor, whereas a lower d/b ratio highlights the greater NHC ← metal π-back donation. Interestingly, in the studies conducted by Ghosh, greater NHC ← metal π-back donation was observed in Pd-NHC complexes exhibiting lower d/b ratios ranging between 2.59 – 3.9913,14 and Au-NHC complexes with d/b ratios ranging between 5.23 – 5.8815,16 as compared to the Ag-NHC complexes with d/b ratios ranging between 7.8 – 12.6811,12,16. This observation could attest to why silver-NHC complexes are particularly better transmetallating agents. The newly emerging interest in the medicinal applications of stable metal NHCs led us to examine the few accounts available in the literature dealing with this area of research. This review will discuss in detail the medicinal applications of various transition metal-NHC complexes including silver, gold, rhodium, ruthenium, and palladium. The antimicrobial, antitumor, and resistance properties, along with proposed mechanisms of action to suppress the bacterial growth or proliferation of tumor cells will be discussed.


Journal of Medicinal Chemistry | 2008

Synthesis, Stability, and Antimicrobial Studies of Electronically Tuned Silver Acetate N-Heterocyclic Carbenes

Khadijah M. Hindi; Tammy J. Siciliano; Semih Durmus; Matthew J. Panzner; Doug A. Medvetz; D. Venkat Reddy; Lisa A. Hogue; Christine E. Hovis; Julia K. Hilliard; Rebekah J. Mallet; Claire A. Tessier; Carolyn L. Cannon; Wiley J. Youngs

A series of methylated imidazolium salts with varying substituents on the 4 and 5 positions of the imidazole ring were synthesized. These salts were reacted with silver acetate to afford their corresponding silver N-heterocyclic carbene (NHC) complexes. These complexes were then evaluated for their stability in water as well as for their antimicrobial efficacy against a variety of bacterial strains associated with cystic fibrosis and chronic lung infections.


Biomaterials | 2009

The antimicrobial efficacy of sustained release silver–carbene complex-loaded l-tyrosine polyphosphate nanoparticles: Characterization, in vitro and in vivo studies

Khadijah M. Hindi; Andrew J. Ditto; Matthew J. Panzner; Douglas A. Medvetz; Daniel S. Han; Christine E. Hovis; Julia K. Hilliard; Jane B. Taylor; Yang H. Yun; Carolyn L. Cannon; Wiley J. Youngs

The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver-carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into L-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.


Metal-based Drugs | 2008

Anticancer Activity of Ag(I) N-Heterocyclic Carbene Complexes Derived from 4,5-Dichloro-1H-Imidazole

Doug A. Medvetz; Khadijah M. Hindi; Matthew J. Panzner; Andrew J. Ditto; Yang H. Yun; Wiley J. Youngs

A class of Ag(I) N-heterocyclic carbene silver complexes, 1–3, derived from 4,5-dichloro-1H-imidazole has been evaluated for their anticancer activity against the human cancer cell lines OVCAR-3 (ovarian), MB157 (breast), and Hela (cervical). Silver complexes 1–3 are active against the ovarian and breast cancer cell lines. A preliminary in vivo study shows 1 to be active against ovarian cancer in mice. The results obtained in these studies warrant further investigation of these compounds in vivo.


Dalton Transactions | 2009

A theobromine derived silver N-heterocyclic carbene: synthesis, characterization, and antimicrobial efficacy studies on cystic fibrosis relevant pathogens

Matthew J. Panzner; Khadijah M. Hindi; Brian D. Wright; Jane B. Taylor; Daniel S. Han; Wiley J. Youngs; Carolyn L. Cannon

The increasing incidence of multidrug-resistant (MDR) pulmonary infections in the cystic fibrosis (CF) population has prompted the investigation of innovative silver based therapeutics. The functionalization of the naturally occurring xanthine theobromine at the N(1) nitrogen atom with an ethanol substituent followed by the methylation of the N(9) nitrogen atom gives the N-heterocyclic carbene precursor 1-(2-hydroxyethyl)-3,7,9-trimethylxanthinium iodide. The reaction of this xanthinium salt with silver acetate produces the highly hydrophilic silver carbene complex SCC8. The in vitro antimicrobial efficacy of this newly synthesized complex was evaluated with excellent results on a variety of virulent and MDR pathogens isolated from CF patients. A comparative in vivo study between the known caffeine derived silver carbene SCC1 and SCC8 demonstrated the ability of both complexes to improve the survival rates of mice in a pneumonia model utilizing the clinically isolated infectious strain of Pseudomonas aeruginosa PA M57-15.


Antimicrobial Agents and Chemotherapy | 2009

In Vitro and Murine Efficacy and Toxicity Studies of Nebulized SCC1, a Methylated Caffeine-Silver(I) Complex, for Treatment of Pulmonary Infections

Carolyn L. Cannon; Lisa A. Hogue; Ravy K. Vajravelu; George H. Capps; Aida Ibricevic; Khadijah M. Hindi; Aysegul Kascatan-Nebioglu; Michael J. Walter; Steven L. Brody; Wiley J. Youngs

ABSTRACT The expanding clinical challenge of respiratory tract infections due to resistant bacteria necessitates the development of new forms of therapy. The development of a compound composed of silver coupled to a methylated caffeine carrier (silver carbene complex 1 [SCC1]) that demonstrated in vitro efficacy against bacteria, including drug-resistant organisms, isolated from patients with respiratory tract infections was described previously. The findings of current in vitro studies now suggest that bactericidal concentrations of SCC1 are not toxic to airway epithelial cells in primary culture. Thus, it was hypothesized that SCC1 could be administered by the aerosolized route to concentrate delivery to the lung while minimizing systemic toxicity. In vivo, aerosolized SCC1 delivered to mice resulted in mild aversion behavior, but it was otherwise well tolerated and did not cause lung inflammation following administration over a 5-day period. The therapeutic efficacy of SCC1 compared to that of water was shown in a 3-day prophylaxis protocol, in which mice infected with a clinical strain of Pseudomonas aeruginosa had increased survival, decreased amounts of bacteria in the lung, and a lower prevalence of bacteremia. Similarly, by using an airway infection model in which bacteria were impacted in the airways by agarose beads, the administration of SCC1 was significantly superior to water in decreasing the lung bacterial burden and the levels of bacteremia and markers of airway inflammation. These observations indicate that aerosolized SCC1, a novel antimicrobial agent, warrants further study as a potential therapy for bacterial respiratory tract infections.


Journal of the American Chemical Society | 2005

Silver(I)−Imidazole Cyclophane gem-Diol Complexes Encapsulated by Electrospun Tecophilic Nanofibers: Formation of Nanosilver Particles and Antimicrobial Activity

Abdulkareem Melaiye; Zhaohui Sun; Khadijah M. Hindi; Amy Milsted; Daniel Ely; Darrell H. Reneker; Claire A. Tessier; Wiley J. Youngs


Journal of Medicinal Chemistry | 2006

Synthesis from caffeine of a mixed N-heterocyclic carbene-silver acetate complex active against resistant respiratory pathogens

Aysegul Kascatan-Nebioglu; Abdulkareem Melaiye; Khadijah M. Hindi; Semih Durmus; Matthew J. Panzner; Lisa A. Hogue; Rebekah J. Mallett; Christine E. Hovis; Marvin Coughenour; Seth D. Crosby; Amy Milsted; Daniel Ely; Claire A. Tessier; Carolyn L. Cannon; Wiley J. Youngs


Journal of Organometallic Chemistry | 2011

Synthesis and anticancer properties of gold(I) and silver(I) N-heterocyclic carbene complexes

Tammy J. Siciliano; Michael C. Deblock; Khadijah M. Hindi; Semih Durmus; Matthew J. Panzner; Claire A. Tessier; Wiley J. Youngs


Chemical Communications | 2010

Shell crosslinked nanoparticles carrying silver antimicrobials as therapeutics

Yali Li; Khadijah M. Hindi; Kristin M. Watts; Jane B. Taylor; Ke Zhang; Zicheng Li; David A. Hunstad; Carolyn L. Cannon; Wiley J. Youngs; Karen L. Wooley

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Carolyn L. Cannon

University of Texas Southwestern Medical Center

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Christine E. Hovis

Washington University in St. Louis

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Julia K. Hilliard

Washington University in St. Louis

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Daniel S. Han

Washington University in St. Louis

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