High‐Purity Discrete PEG‐Oligomer Crystals Allow Structural Insight

French, Alister C.; Thompson, Amber L.; Davis, Benjamin G.

doi:10.1002/ange.200804623

Cited by 24 publications

(48 citation statements)

References 45 publications

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“…It may be that the relatively high proportion of OH end groups in the study in Ref. 2 influenced the conformation, whereas our CH 3 O‐ end‐capped material possesses interactions more closely resembling long‐chain PEO.…”

Section: Methodsmentioning

confidence: 77%

Synthesis of Poly(ethylene oxide) Approaching Monodispersity

2014

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Polydispersity in polymers hinders fundamental understanding of their structure-property relationships and prevents them from being used in fields like medicine, where polydispersity affects biological activity. The polydispersity of relatively short-chain poly(ethylene oxide) [(CH2CH2O2)n; PEO] affects its biological activity, for example, the toxicity and efficacy of PEOylated drugs. As a result, there have been intensive efforts to reduce the dispersity as much as possible (truly monodispersed materials are not possible). Here we report a synthetic procedure that leads to an unprecedented low level of dispersity. We also show for the first time that it is possible to discriminate between PEOs differing in only 1 ethylene oxide (EO) unit, essential in order to verify the exceptionally low levels of dispersity achieved here. It is anticipated that the synthesis of poly(ethylene oxide) approaching monodispersity will be of value in many fields where the applications are sensitive to the distribution of molar mass.

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Section: Methodsmentioning

confidence: 77%

Synthesis of Poly(ethylene oxide) Approaching Monodispersity

2014

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“…oligoethylenes,3 oligo(ε‐aminocaproic acid),4 oligo(β‐hydroxybutanoic acid)5a). It is also a breakthrough to have, for the first time, a single‐crystal X‐ray structure of an oligoethylene glycol derivative consisting of M ‐ and P ‐3 10 ‐helical building blocks 1. However, readers will have gained the impression that this is the first crystallographic demonstration of the backbone structure of (CH 2 CH 2 O) n chains; this is false, for the reasons outlined herein.…”

mentioning

confidence: 99%

“…At the beginning of 2009, in an Angewandte Communication, the preparation of monodisperse oligomers of ethylene oxide (up to 48 units), the isolation of single crystals of hexadecaethylene glycol monomethyl ether 1 , and its X‐ray crystal structure were reported 1…”

mentioning

confidence: 99%

“…Our common ongoing interests in the conformation of PEG1 and of oligoethylene glycol conjugates5b have led to continued examination of the pertinent literature. We detail here how and why original and subsequent searches missed reports from the 1960s and 1970s on the subject 6.…”

mentioning

confidence: 99%

“…Since Beilstein does not really cover polymers, Chemical Abstracts databases are the first choice. Prior to the submission of the original paper, searches using SciFinder Scholar on oligoethylene glycols,1 both on structure and topic (and mutually refined), had failed to reveal reference [6a]. A “Topic Search” in SciFinder Scholar with the term “backbone of polyethylene glycol” retrieved 859 references (June 8, 2009); refinement with the term “helix (helical)” reduced this number to seven, none of which was directly relevant; likewise, a refinement with “gauche” failed.…”

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confidence: 99%

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Polymer Backbone Conformation—A Challenging Task for Database Information Retrieval

et al. 2009

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crystal structure analysis · polyethylene glycol · polymers · structure databasesAt the beginning of 2009, in an Angewandte Communication, the preparation of monodisperse oligomers of ethylene oxide (up to 48 units), the isolation of single crystals of hexadecaethylene glycol monomethyl ether 1, and its X-ray crystal structure were reported.[1]We believe that this is a widely relevant result, in view of the practice of attaching polyethylene glycol (PEG) chains (usually as a Gaussian distribution of chain lengths) to therapeutic proteins, peptides, and small molecules (PEGylation) to influence stability, immunogenicity, solubility, pharmacokinetics, and mode of action.[2] The construction of such large monodisperse oligoethylene glycol derivatives requires substantial effort as is true in other cases (cf. oligoethylenes, [3] oligo(e-aminocaproic acid), [4] oligo(b-hydroxybutanoic acid) [5a] ). It is also a breakthrough to have, for the first time, a single-crystal X-ray structure of an oligoethylene glycol derivative consisting of M-and P-3 10 -helical building blocks. [1] However, readers will have gained the impression that this is the first crystallographic demonstration of the backbone structure of (CH 2 CH 2 O) n chains; this is false, for the reasons outlined herein.Our common ongoing interests in the conformation of PEG [1] and of oligoethylene glycol conjugates [5b] have led to continued examination of the pertinent literature. We detail here how and why original and subsequent searches missed reports from the 1960s and 1970s on the subject.[6] This, in turn, will highlight some of the current challenges for chemical and crystallographic database construction, interrogation, and information retrieval. Our purpose here is, firstly, to bring the communitys attention to this early work regarding PEG crystal structures determined from fibers [6a,b] and freeze-dried [6c] particles, and secondly, to point out problems that can be encountered in modern electronic data retrieval, especially for certain extended polymeric structures, as well as suggest strategies for improved structure retrieval.It is known that X-C-C-Y systems (X,Y = electronegative heteroatoms) often prefer synclinal over antiplanar conformations; [7] this "gauche effect" [8] leads naturally to a helical backbone conformation in PEG. There are scattered statements in textbooks about the "well-known" helical backbone of PEG, [9][10][11] but how does one find the corresponding original literature?Since Beilstein does not really cover polymers, Chemical Abstracts databases are the first choice. Prior to the submission of the original paper, searches using SciFinder Scholar on oligoethylene glycols, [1] both on structure and topic (and mutually refined), had failed to reveal reference [6a]. A "Topic Search" in SciFinder Scholar with the term "backbone of polyethylene glycol" retrieved 859 references (June 8, 2009); refinement with the term "helix (helical)" reduced this number to seven, none of which was directly relevant; likewise, a refineme...

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