Case Report Motor Vehicle Collision Patient with Simultaneous Duodenal Transection and Thoracic Aorta Injury: A Case Report and Review of the Literature

Blunt polytrauma can present complex management decisions. Here we report the case of a 31-year-old male involved in a high speed motor vehicle collision resulting in both duodenal and thoracic aorta injury that was managed collaboratively between the trauma, vascular, and cardiothoracic surgical teams. The patient went on to a full recovery. We also review the management of such injuries which has evolved over the past two decades resulting in less morbidity and mortality

An experimental and computational analysis on the differential role of the positional isomers of symmetric bis-2-(pyridyl)-1H-benzimidazoles as DNA binding agents

Three symmetrical positional isomers of bis-2-(n-pyridyl)-1H-benzimidazoles (n = 2, 3, 4) were synthesized and DNA binding studies were performed with these isomeric derivatives. Like bisbenzimidazole compound Hoechst 33258, these molecules also demonstrate AT-specific DNA binding. The binding affinities of 3-pyridine (m-pyben) and 4-pyridine (p-pyben) derivatized bisbenzimidazoles to double-stranded DNA were significantly higher compared to 2-pyridine derivatized benzimidazole o-pyben. This has been established by combined experimental results of isothermal fluorescence titration, circular dichroism, and thermal denaturation of DNA. To rationalize the origin of their differential binding characteristics with double-stranded DNA, computational structural analyses of the uncomplexed ligands were performed using ab initio/Density Functional Theory. The molecular conformations of the symmetric head-to-head bisbenzimidazoles have been computed. The existence of intramolecular hydrogen bonding was established in o-pyben, which confers a conformational rigidity to the molecule about the bond connecting the pyridine and benzimidazole units. This might cause reduction in its binding affinity to double-stranded DNA compared to its para and meta counterparts. Additionally, the predicted stable conformations for p-, m-, and o-pyben at the B3LYP/6-31G∗ and RHF/6-31G∗ levels were further supported by experimental pKa determination. The results provide important information on the molecular recognition process of such symmetric head to head bisbenzimidazoles toward duplex DNA

An Experimental and Computational Analysis on the Differential Role of the Positional Isomers of Symmetric Bis-2-(pyridyl)-1H-benzimidazoles as DNA Binding Agents

Three symmetrical positional isomers of bis-2-(n-pyridyl)-1H-benzimidazoles (n = 2, 3, 4) were synthesized and DNA binding studies were performed with these isomeric derivatives. Like bisbenzimidazole compound Hoechst 33258, these molecules also demonstrate AT-specific DNA binding. The binding affinities of 3-pyridine (m-pyben) and 4-pyridine (p-pyben) derivatized bisbenzimidazoles to doublestranded DNA were significantly higher compared to 2-pyridine derivatized benzimidazole o-pyben. This has been established by combined experimental results of isothermal fluorescence titration, circular dichroism, and thermal denaturation of DNA. To rationalize the origin of their differential binding characteristics with double-stranded DNA, computational structural analyses of the uncomplexed ligands were performed using ab initio/Density Functional Theory. The molecular conformations of the symmetric head-to-head bisbenzimidazoles have been computed. The existence of intramolecular hydrogen bonding was established in o-pyben, which confers a conformational rigidity to the molecule about the bond connecting the pyridine and benzimidazole units. This might cause reduction in its binding affinity to double-stranded DNA compared to its para and meta counterparts. Additionally, the predicted stable conformations for p-, m-, and o-pyben at the B3LYP/6-31G* and RHF/6-31G* levels were further supported by experimental $pK_a$ determination. The results provide important information on the molecular recognition process of such symmetric head to head bisbenzimidazoles toward duplex DNA

Computational study on hydroxybenzotriazoles as reagents for ester hydrolysis

1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate potent esterolytic activity toward activated esters such as p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic micelles at pH 8.2 and 25 °C. The deprotonated anionic forms of such reagents act as reactive species in the hydrolysis of ester. To rationalize the origin of their nucleophilic character, a detailed ab initio/DFT computational study has been performed on 1-5 along with additional hydroxybenzotriazole derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their corresponding bases are discussed in detail. All calculations were carried out using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab initio/DFT (B3LYP) using 6-31G∗ and 6-31+G∗ basis sets. Free energy of protonation ('fep') of the 1-hydroxybenzotriazoles (1-13), free energy of solvation ΔGaq, and the corresponding pKa values have been calculated. Solvation-free energies were calculated using density functional theory and the polarizable continuum model. In addition, to examine the reliability of calculated fep, benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been computed as reference systems using different methods and basis sets, the experimental feps of which are known. Our experimental finding shows that the compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP and PNPH. This has been predicted from our calculated fep, pKa, and natural charge analysis results as well. In general, the introduction of electron-withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of pKa and fep. As the pKa values are lowered, a greater percentage of such hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2. Since the anionic forms are nucleophilic, pKa lowering should enhance their ester cleaving capacity. However, such substitution also decreases the charge density on the catalytically active oxido atom (O7). Taking these two factors together, the derivatives are only modestly better nucleophiles in comparison to the parent 1-hydroxybenzotriazole. Interestingly, the introduction of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom (O7) of 1-hydroxybenzotriazoles

Structure-activity investigation on the gene transfection properties of cardiolipin mimicking gemini lipid analogues

A structure-activity relationship has been explored on the gene transfection efficiencies of cardiolipin mimicking gemini lipid analogues upon variation of length and hydrophilicity of the spacer between the cationic ammonium headgroups and lipid hydrocarbon chain lengths. All the gemini lipids were found to be highly superior in gene transfer abilities as compared to their monomeric lipid and a related commercially available formulation. Pseudoglyceryl gemini lipids bearing an oxyethylene (-CH2-(CH2-O-CH2)m-CH2-) spacer were found to be superior gene transfecting agents as compared to those bearing polymethylene (-CH2)m-) spacers. The major characteristic feature of the present set of gemini lipids is their serum compatibility, which is most often the major hurdle in liposome-mediated gene delivery

Computational Study on Hydroxybenzotriazoles as Reagents for Ester Hydrolysis

1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate potent esterolytic activity toward activated esters such as p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic micelles at pH 8.2 and 25°C. The deprotonated anionic forms of such reagents act as reactive species in the hydrolysis of ester. To rationalize the origin of their nucleophilic character, a detailed ab initio/DFT computational study has been performed on 1-5 along with additional hydroxybenzotriazole derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their corresponding bases are discussed in detail. All calculations were carried out using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab initio/ DFT (B3LYP) using 6-31G* and 6-31+G* basis sets. Free energy of protonation (fep) of the 1-hydroxybenzotriazoles (1-13), free energy of solvation $\Delta$$G$_a_q, and the corresponding $pK_a$ values have been calculated. Solvation-free energies were calculated using density functional theory and the polarizable continuum model. In addition, to examine the reliability of calculated fep, benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been computed as reference systems using different methods and basis sets, the experimental feps of which are known. Our experimental finding shows that the compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP and PNPH. This has been predicted from our calculated fep, $pK_a$, and natural charge analysis results as well. In general, the introduction of electron-withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of $pK_a$ and fep. As the $pK_a$ values are lowered, a greater percentage of such hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2. Since the anionic forms are nucleophilic, $pK_a$ lowering should enhance their ester cleaving capacity. However, such substitution also decreases the charge density on the catalytically active oxido atom $(O_7)$. Taking these two factors together, the derivatives are only modestly better nucleophiles in comparison to the parent 1-hydroxybenzotriazole. of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom $(O_7)$ of 1-hydroxybenzotriazoles

Structure-Activity Investigation on the Gene Transfection Properties of Cardiolipin Mimicking Gemini Lipid Analogues

A structure-activity relationship has been explored on the gene transfection efficiencies of cardiolipin mimicking gemini lipid analogues upon variation of length and hydrophilicity of the spacer between the cationic ammonium headgroups and lipid hydrocarbon chain lengths. All the gemini lipids were found to be highly superior in gene transfer abilities as compared to their monomeric lipid and a related commercially available formulation.Pseudoglyceryl gemini lipids bearing an oxyethylene $(-CH_2-(CH_2-O-CH_2) m-CH_2-)$ spacer were found to be superior gene transfecting agents as compared to those bearing polymethylene $(-CH_2)_m-)$ spacers. The major characteristic feature of the present set of gemini lipids is their serum compatibility, which is most often the major hurdle in liposome-mediated gene delivery

Synthesis of novel dimeric cationic lipids based on an aromatic backbone between the hydrocarbon chains and headgroup

Seven dimeric cationic lipids possessing an aromatic anchor between the hydrocarbon chains and cationic headgroup have been synthesized. The spacers in these lipids vary in length, hydrophobicity and flexibility. The synthesis, membrane-forming properties and complexation with plasmid DNA (lipoplex formation) are briefly described

Effect of the hydrocarbon chain and polymethylene spacer lengths on gene transfection efficacies of gemini lipids based on aromatic backbone

Design, syntheses, and gene delivery efficacies of fifteen novel gemini (dimeric) and three monomeric cationic lipids anchored on an aromatic backbone have been described. Each new lipid has been used for liposome formation, and optimal formulations were used to determine the structure-activity correlation of the gene transfection efficacies of these lipids in HeLa and HT1080 cells. The results of the present investigation bring out the effect of hydrocarbon chain lengths and the length of the spacer between the headgroups on gene transfection efficiencies of the cationic gemini lipids based on aromatic backbone. The lipids bearing n-C14H29 hydrocarbon chain lengths have been found to be the best transfecting agents compared to their counterparts with n-C16H33 and n-C12H25chains in HeLa cells. On the other hand, in HT1080 cells, the lipids based on n-C12H25 and n-C14H29 chains were found to be more potent transfecting agents than lipids possessing n-C16H33 chains. Transmission electron microscopy examination revealed the existence of spherical lipid-DNA complexes