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Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces./
Author:	Poloni, Laura N.
Description:	1 online resource (361 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 78-08(E), Section: B.
Contained By:	Dissertation Abstracts International78-08B(E).
Subject:	Molecular chemistry. -
Online resource:	click for full text (PQDT)
ISBN:	9781369652086

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces.
Poloni, Laura N.

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces. - 1 online resource (361 pages)

Source: Dissertation Abstracts International, Volume: 78-08(E), Section: B.

Thesis (Ph.D.)

Includes bibliographical references

The organization of atoms and molecules into crystalline forms is ubiquitous in nature and has been critical to the development of many technologies on which modern society relies. Classical crystal growth theory can describe atomic crystal growth, however, a description of molecular crystal growth is lacking. Molecular crystals are often characterized by anisotropic intermolecular interactions and dissymmetric crystal surfaces with anisotropic growth rates along different crystallographic directions. This thesis describes combination of experimental and computational techniques to relate crystal structure to surface structure and observed growth rates. Molecular imposters, also known as tailor-made impurities, can be used to control crystal growth for practical applications such as inhibition of pathological crystals, but can also be used to understand site specificity at crystal growth surfaces.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9781369652086Subjects--Topical Terms:

1179636
Molecular chemistry.
Index Terms--Genre/Form:

554714
Electronic books.

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces.
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245 1 0 $a Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces.
264 0 $c 2017
300 $a 1 online resource (361 pages)
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500 $a Source: Dissertation Abstracts International, Volume: 78-08(E), Section: B.
500 $a Adviser: Michael D. Ward.
502 $a Thesis (Ph.D.) $c New York University $d 2017.
504 $a Includes bibliographical references
520 $a The organization of atoms and molecules into crystalline forms is ubiquitous in nature and has been critical to the development of many technologies on which modern society relies. Classical crystal growth theory can describe atomic crystal growth, however, a description of molecular crystal growth is lacking. Molecular crystals are often characterized by anisotropic intermolecular interactions and dissymmetric crystal surfaces with anisotropic growth rates along different crystallographic directions. This thesis describes combination of experimental and computational techniques to relate crystal structure to surface structure and observed growth rates. Molecular imposters, also known as tailor-made impurities, can be used to control crystal growth for practical applications such as inhibition of pathological crystals, but can also be used to understand site specificity at crystal growth surfaces.
520 $a The first part of this thesis builds on previous real-time in situ atomic force microscopy (AFM) observations of dislocation-actuated growth on the morphologically significant face of hexagonal L-cystine crystals, which aggregate in vivo to form kidney stones in patients suffering from cystinuria. The inhibitory effect of various L-cystine structural mimics (a.k.a. molecular imposters) was investigated through experimental and computational methods to identify the key structural factors responsible for molecular recognition between molecular imposters and L-cystine crystal surface sites. The investigation of L-cystine crystal growth in the presence of molecular imposters through a combination of kinetic analysis using in situ AFM, morphology analysis and birefringence measurements of bulk crystals, and molecular modeling of imposter binding to energetically inequivalent surface sites revealed that different molecular imposters inhibited crystal growth by a Cabrera-Vermilyea pinning mechanism and that imposters bind to a single binding site on the dissymmetric {1000} L-cystine surfaces. Collectively, these findings identify the key structural factors responsible for molecular recognition between molecular imposters and L-cystine crystal step sites, thereby articulating a strategy for stone prevention based on molecular design.
520 $a The second part of this thesis describes the crystal growth and inhibition of a P2X3 receptor antagonist, denoted as DAPSA, recently reported as a non-opioid treatment of chronic pain. The low solubility of this compound results in the formation of drug-induced renal calculi (a.k.a. xenostones). in situ AFM of the morphologically significant (011) DAPSA surface revealed dislocation-actuated growth spirals with an anisotropic morphology, behavior that can be attributed to the non-uniform rate of solute attachment to eight crystallographically unique steps of the spiral, a direct consequence of the dissymmetry of this crystal surface. Eighteen molecular imposters were selected from the screening library to systematically investigate the roles of imposter substitute position, size, and functionality on the step velocities along the eight unique crystallographic directions. A non-uniform reduction in step velocities was observed, signaling site discrimination of imposter binding that can be attributed to stereochemical recognition of the imposters at specific crystal sites. The anisotropy of growth inhibition observed in the presence of the various imposters is consistent with binding energies calculated for the thirty-two crystallographically unique kink sites on steps advancing along predominant growth directions. These results provide insight to the design of growth inhibitors for molecular crystalline solids with complex and dissymmetric surfaces, while also suggesting a strategy for formulations containing congeners that can prevent harmful crystal growth in human renal structures.
520 $a The last two crystalline systems discussed in this thesis are two isomorphous crystal systems that are ideal for the study of impurity incorporation at dissymmetric surfaces because their morphology is dominated by dissymmetric {101} growth faces. Growth processes on the dissymmetric (101) surfaces of these crystalline systems were investigated using metadynamics simulations to determine the free energy of adsorption for solute and impurity attachment to different flat, stepped, and kinked (101) surface terminations. Results suggest that growth occurs via a non-Kossel crystal growth mechanism, and highlights the need for dissymmetric surface structures (i.e. steps and kinks) for a higher fidelity in the orientation of adsorbed molecules.
520 $a Overall, the results presented in this thesis suggest that growth of molecular crystals, particularly at dissymmetric surfaces, is complex and requires the combination of several experimental and computational techniques to decipher the mechanisms responsible for growth phenomena. The use of molecular imposters to inhibit growth can be useful for the development of therapeutics for pathological crystals, but can also inform processes by which crystal growth occurs at complex surfaces as a result of their site selectivity.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Molecular chemistry. $3 1179636
650 4 $a Materials science. $3 557839
650 4 $a Physical chemistry. $3 1148725
655 7 $a Electronic books. $2 local $3 554714
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710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a New York University. $b Chemistry. $3 1179635
773 0 $t Dissertation Abstracts International $g 78-08B(E).
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