Vojislava Pophristic

University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, United States

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Publications (18)67.21 Total impact

  • Ara M Abramyan, Zhiwei Liu, Vojislava Pophristic
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    ABSTRACT: Molecular capsules have been extensively used in catalysis, drug delivery, molecular recognition and protection of ligands from degradation. Novel "apple peel" shaped helical arylamide capsules have been experimentally pursued due to their flexible nature and designability. They were found to encapsulate a variety of small molecules. The apple peel shape of the capsules led to a hypothesis that binding and release of ligands involve partial unfolding. However, the exact mechanism is unknown. Using molecular dynamics simulations with our new aryl-amide force field parameters, we identify two low energy barrier binding/release mechanisms, in which the capsule's helical structure is either minimally disturbed or restored quickly (within 100 ps). Furthermore, we determine the effects of ligand sizes, their chemical nature (hydrogen bonding capabilities), and solvents on binding modes and stabilities. Our findings not only support experimental observations but also provide underlying principles that allow for rational design of foldamer capsules.
    Physical Chemistry Chemical Physics 08/2014; · 4.20 Impact Factor
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    ABSTRACT: We examine the conformational preferences of the furan- and thiophene-based arylamides, N-methylfuran-2-carboxamide () and N-methylthiophene-2-carboxamide (), using a combination of computational methods and NMR experiments. The compound choice stems from their use as foldamer building blocks. We quantify the differences in the conformational rigidity of the two compounds, which governs corresponding foldamer conformations. Specifically, we demonstrate the effects of intramolecular hydrogen bonding (H-bonding), geometrical patterns and solvent polarity on arylamide conformations by comparing , and previously studied ortho-methoxy N-methylbenzamide () and ortho-methylthio N-methylbenzamide (). The study reveals that compound , despite its non-optimal S(5)-type H-bond geometry, retains a large portion of the H-bonded (eclipsed) conformation even in polar protic solvents. This behaviour is consistent with the quantum mechanical (QM) torsional energy profile. The percentages of H-bonded conformers that retains are just slightly smaller than those of , which has a stronger S(6)-type H-bond. As for and , the replacement of the O atom in by an S atom in results in a 70-90% loss of the H-bonded conformer in solution. However, the equivalent O to S replacement in (leading to ) causes only 15-30% loss of the eclipsed conformers in . Therefore, conformational preferences of are very different from , in contrast to the similarity between and . This study shows how the interplay of several forces modulates the conformational flexibility of arylamides. It also attests the strategy we are developing, which leads to accurate prediction of foldamer structure. The vital component of this strategy is the re-parameterization of critical force field parameters based on QM potential energy profiles, as well as validation of these parameters using experimental data in solution.
    Physical Chemistry Chemical Physics 06/2013; · 4.20 Impact Factor
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  • Zhiwei Liu, Alexey Teslja, Vojislava Pophristic
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    ABSTRACT: The aromatic oligoamide (arylamide) foldamer class, characterized by the repetitive aromatic-amide pattern, is one of the most intensively studied foldamer families. In this article, the potential energy profiles with regard to torsional motions around the two types of aromatic-amide bonds (C(a)-C(p) and C(a)-N) are obtained at the B3LYP/6-311G(d,p) level of theory. The effect of ortho substituents with different hydrogen bonding abilities (OCH(3) vs. SCH(3) ) on the torsional potential profiles is analyzed in detail. There are several findings that have implications in foldamer design. The ortho-SCH(3) substituent on the benzene ring produces a much more flexible arylamide backbone with respect to the OCH(3) substituent, as it restricts the C(a)-C(p) torsion to a lesser extent. Interestingly, the rigidifying effect of the ortho-SCH(3) substituent on the C(a)-N torsion is very similar to that of the OCH(3) substituent on the same linkage type. In addition, the SCH(3) substituent prefers a perpendicular orientation with respect to the benzene ring to the in-plane one. It is also found that reparameterization of the corresponding torsional parameters, sometimes specific to the ortho substituent type, in the general amber force field is necessary for an accurate description of the backbone torsions in arylamides. Six sets of partial charge/torsional parameters for each linkage (C(a)-C(p) or C(a)-N)/substituent (OCH(3) or SCH(3) ) combination are obtained based on the ab initio torsional profiles. Initial assessments of these parameters show good agreement with the ab initio results.
    Journal of Computational Chemistry 04/2011; 32(9):1846-58. · 3.84 Impact Factor
  • Article: An
    Zhiwei Liu, Alexey Teslja, Vojislava Pophristic
    Journal of Computational Chemistry. 01/2011; 32:1846-1858.
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    ABSTRACT: As a part of our systematic study of foldamer structural elements, we analyze and quantify the conformational behavior of two model compounds based on a frequently used class of aromatic oligoamide building blocks. Combining computational and NMR approaches, we investigate ortho-fluoro- and ortho-chloro-N-methylbenzamide. Our results indicate that the -F substituent in an ortho position can be used to fine-tune the rigidity of the oligomer backbone. It provides a measurably attenuated but still considerably strong hydrogen bond (H-bond) to the peptide group proton when compared to the -OCH3 substituent in the same position. On the other hand, the ortho-Cl substituent does not impose significant restrictions on the flexibility of the backbone. Its effect on the final shape of an oligomer is likely governed by its size rather than by noncovalent intramolecular interactions. Furthermore, the effect of solvent on the conformational preferences of these building blocks has been quantified. The number of intramolecularly H-bonded conformations decreases significantly when going from nonprotic to protic environments. This study will facilitate rational design of novel arylamide foldamers.
    The Journal of Physical Chemistry B 10/2009; 113(38):12809-15. · 3.61 Impact Factor
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    ABSTRACT: We combine molecular modeling and NMR methods to better understand intramolecular hydrogen bonding (H-bonding) in a frequently used arylamide foldamer building block, ortho-methoxy-N-methylbenzamide. Our results show that solvents have a profound influence on the cumulative number and stabilizing effects of intramolecular H-bonds, and thus conformational preferences, of foldamers based on this compound. While intramolecular H-bonds are conserved in aprotic environments, they are significantly disrupted in protic solvents. Furthermore, these solvent effects can be accurately quantified using the computational approach presented here. The results could have significant implications in foldamer design, particularly for applications in aqueous environments.
    The Journal of Physical Chemistry B 05/2009; 113(20):7041-4. · 3.61 Impact Factor
  • Niny Rao, Marian N. Holerca, Michael L. Klein, Vojislava Pophristic
    ChemInform 01/2008; 39(8).
  • Niny Rao, Marian N. Holerca, Vojislava Pophristic
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    ABSTRACT: Despite widespread zirconium use ranging from nuclear technology to antiperspirants, important aspects of its solvation chemistry, such as the nature of small zirconium(IV) hydroxy cluster ions in aqueous solution, are not known due to the complexity of the zirconium aqueous chemistry. Using a combination of Car−Parrinello molecular dynamics simulations and conventional quantum mechanical calculations, we have determined the structural characteristics and analyzed the aqueous solution dynamics of the two smallest zirconium(IV) cluster species possible, i.e., the dimer and trimer. Our study points to and provides detailed geometrical information for a stable structural motif for building zirconium polymers, the Zr(OH)2Zr bridging unit with 7−8 coordinated Zr ions, which, however, cannot be used to construct a stable structure for the trimer. We find that a stacked trimer, not featuring this motif, is a possible structure, though not a very stable one, shedding new light on this species, and its possible importance in the aqueous chemistry of Zr4+ ion.
    Journal of Chemical Theory and Computation - J CHEM THEORY COMPUT. 12/2007; 4(1).
  • Niny Rao, Marian N Holerca, Michael L Klein, Vojislava Pophristic
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    ABSTRACT: The Zr(4+) tetramer, [Zr(4)(OH)(8)(H(2)O)(16)](8+), is thought to be the major component of the Zr(4+) polymer system in aqueous solution, present as a dominant ionic cluster species compared to other Zr(4+) clusters under various experimental conditions. Despite widespread applications of zirconium, the structure and dynamics of the tetramer in aqueous solution are not well understood. We conducted a combination of ab initio molecular dynamics and quantum mechanical studies in the gas phase and aqueous solution and related our results to the available experimental data to provide atom-level information on the behavior of this species in aqueous solution. Our simulations indicate that the tetramer structure is stable on the picosecond time scale in an aqueous environment and that it is of a planar form, comprising eight-coordinated Zr(4+) ions with an antiprism/irregular dodecahedron ligand arrangement. In combination with our studies of Zr(4+) dimer and trimer clusters, our results provide detailed geometrical information on structural motifs for building zirconium polymers and suggest a possible polymerization path.
    The Journal of Physical Chemistry A 12/2007; 111(45):11395-9. · 2.77 Impact Factor
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    ABSTRACT: Using DFT methods, we have determined intramolecular parameters for an important class of arylamide polymers displaying antimicrobial and anticoagulant inhibitory properties. A strong link has been established between these functions and the conformation that the polymers adopt in solution and at lipid bilayer interfaces. Thus, it is imperative for molecular dynamics simulations designed to probe the conformational behavior of these systems to accurately describe the torsional degrees of freedom. Standard force fields were shown to be deficient in this respect. Therefore, we have computed the relevant torsional energy profiles using a series of constrained geometry optimizations. We have also determined electrostatic parameters using our results in combination with standard RESP charge optimization. Force constants for bond and angle potentials were calculated by iteratively matching quantum and classical normal modes via a Monte Carlo scheme. The resulting new set of parameters accurately described the conformation and dynamical behavior of the arylamide polymers.
    Journal of Computational Chemistry 05/2006; 27(6):693-700. · 3.84 Impact Factor
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    ABSTRACT: Using quantum chemistry plus ab initio molecular dynamics and classical molecular dynamics methods, we address the relationship between molecular conformation and the biomedical function of arylamide polymers. Specifically, we have developed new torsional parameters for a class of these polymers and applied them in a study of the interaction between a representative arylamide and one of its biomedical targets, the anticoagulant drug heparin. Our main finding is that the torsional barrier of a C(aromatic)-C(carbonyl) bond increases significantly upon addition of an o-OCH2CH2NH3+ substituent on the benzene ring. Our molecular dynamics studies that are based on the original general AMBER force field (GAFF) and GAFF modified to include our newly developed torsional parameters show that the binding mechanism between the arylamide and heparin is very sensitive to the choice of torsional potentials. Ab initio molecular dynamics simulation of the arylamide independently confirms the degree of flexibility we obtain by classical molecular dynamics when newly developed torsional potentials are used.
    The Journal of Physical Chemistry B 04/2006; 110(8):3517-26. · 3.61 Impact Factor
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    ABSTRACT: We have applied molecular dynamics to investigate the structural properties and activity of recently synthesized amphiphilic polymethacrylate derivatives, designed to mimic the antimicrobial activity of natural peptides. The composition, molecular weight, and hydrophobicity (ratio of hydrophobic and cationic units) of these short copolymers can be modulated to achieve structural diversity, which is crucial in controlling the antimicrobial activity. We have carried out all-atom molecular dynamics to systematically investigate the conformations adopted by these copolymers in water and at the water-lipid interface as a function of sequence and the chemical nature of the monomers. For two sequences, we observe partial insertion into the bilayer. Formation of strong interactions between the lipid headgroups and the amine groups of the polymers assists in the initial association with the lipids. However, the primary driving force for the observed partial insertion appears to be the hydrophobic effect. Our results indicate sensitive dependence of the overall shape on the sequence, suggesting that experimentally observed changes in activity can be correlated with particular sequences, providing an avenue for rational design.
    Journal of the American Chemical Society 03/2006; 128(6):1778-9. · 10.68 Impact Factor
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    Angewandte Chemie International Edition 11/2005; 44(41):6685-9. · 11.34 Impact Factor
  • Angewandte Chemie 10/2005; 117(41):6757-6757.
  • Angewandte Chemie International Edition 01/2005; 44(41):6599-6599. · 11.34 Impact Factor
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    ABSTRACT: The Al13 polymer, Al13O4(OH)24(H2O)12Cl7, is thought to be a major component of the aluminum chlorohydrate (ACH) polymer system. Although it plays important roles in various aluminum chlorohydrate applications, its structure is not well understood. We combine ab initio molecular dynamics simulations in both the gas-phase and aqueous solution, with small angle X-ray scattering experiments on a bulk ACH sample to determine the structure of Al13-mer. We find that Al13 entity is roughly spherical (10 Å diameter), with a central tetrahedral Al3+ ion surrounded by four shells consisting of O, OH and H2O groups. Our ab initio molecular dynamics studies indicate that such a structure is stable on the picosecond time scale in an aqueous environment.
    Physical Chemistry Chemical Physics 06/2004; 6. · 4.20 Impact Factor
  • Vojislava Pophristic, Michael L. Klein
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    ABSTRACT: Despite many experimental studies, the structure of aluminum chlorohydrate system is not well understood due to its complexity. Using a combination of Car Parrinello molecular dynamics and ab initio methods, we conclusively determine the structures of aluminum chlorohydrate monomer, dimer, trimer, and hexamer species. Contrary to the common assumption that the Al coordination shell in these compounds consists of OH groups and H2O molecules only, we find that Cl- ion incorporation in the octahedral structure of aluminum chlorohydrate monomer, dimer, and trimer increases their stability in the gas phase. The hexamer gas-phase structure is predicted to be built from both penta- and hexacoordinated Al3+ ions. Gas-phase optimized dimer and hexamer complexes are found to exhibit stable behavior in water solutions in the course of 7−8 ps of a Car Parrinello molecular dynamics run.
    Journal of Physical Chemistry A - J PHYS CHEM A. 12/2003; 108(1).

Publication Stats

80 Citations
67.21 Total Impact Points

Institutions

  • 2005–2014
    • University of the Sciences in Philadelphia
      • Department of Chemistry and Biochemistry
      Philadelphia, Pennsylvania, United States
  • 2006
    • University of California, San Diego
      • Department of Chemistry and Biochemistry
      San Diego, CA, United States
  • 2004–2006
    • University of Pennsylvania
      • Department of Chemistry
      Philadelphia, PA, United States