Poly(ethylene glycol) (PEG) is a biocompatible, flexible, and hydrophilic polymer that is widely applied in numerous fields. Especially in pharmaceutical research, PEG is used as a bioconjugate agent for PEG-ylated drugs. A well-defined structure is crucial, since dispersity affects biological activity (e.g., toxicity and efficacy). Thus, intensive efforts to develop synthetic protocols approaching uniformity have been made in recent decades. Different approaches utilizing iterative step-by-step synthesis procedures have yielded promising results, and improvement is still ongoing. In this comparative study, we adopted several procedures for the preparation of uniform PEGs in combination with careful characterization, including size exclusion chromatography (SEC) analysis, which has yet to be reported. Oligo(ethylene glycol)s up to the dodecamer were synthesized. The results obtained were compared in terms of yield and purity with those previously reported in the literature. We clearly show the importance of SEC analysis with high separation capacity in the oligomer range for the synthesis of short-chain oligo(ethylene glycol)s. Herein, several synthetic procedures for the synthesis of uniform PEGs were compared. The importance of SEC as analytical method for the determination of the precise structure and purity of uniform PEGs was shown by means of simple symmetry peak analysis, revealing that SEC can detect contaminations of only 2% of oligomers with only one repeat unit difference.

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均质聚（乙二醇）：一项比较研究

聚（乙二醇）（PEG）是一种生物相容性、柔性和亲水性的聚合物，广泛应用于众多领域。特别是在药物研究中，PEG 被用作 PEG 化药物的生物偶联剂。明确定义的结构至关重要，因为分散性会影响生物活性（例如，毒性和功效）。因此，近几十年来，人们为开发接近均匀性的合成方案做出了大量努力。利用迭代逐步合成程序的不同方法已经产生了有希望的结果，并且改进仍在进行中。在这项比较研究中，我们采用了几种方法来制备均匀的 PEG，并结合仔细的表征，包括尚未报道的尺寸排阻色谱 (SEC) 分析。合成了多达十二聚体的低聚（乙二醇）。获得的结果在产率和纯度方面与以前在文献中报道的结果进行了比较。我们清楚地表明了在低聚物范围内具有高分离能力的 SEC 分析对于合成短链低聚（乙二醇）的重要性。在此，比较了几种合成均匀 PEG 的合成程序。通过简单的对称峰分析显示了 SEC 作为确定均匀 PEG 的精确结构和纯度的分析方法的重要性，表明 SEC 可以检测仅 2% 的低聚物的污染，并且只有一个重复单元差异。我们清楚地表明了在低聚物范围内具有高分离能力的 SEC 分析对于合成短链低聚（乙二醇）的重要性。在此，比较了几种合成均匀 PEG 的合成程序。通过简单的对称峰分析显示了 SEC 作为确定均匀 PEG 的精确结构和纯度的分析方法的重要性，表明 SEC 可以检测仅 2% 的低聚物的污染，并且只有一个重复单元差异。我们清楚地表明了在低聚物范围内具有高分离能力的 SEC 分析对于合成短链低聚（乙二醇）的重要性。在此，比较了几种合成均匀 PEG 的合成程序。通过简单的对称峰分析显示了 SEC 作为确定均匀 PEG 的精确结构和纯度的分析方法的重要性，表明 SEC 可以检测仅 2% 的低聚物的污染，并且只有一个重复单元差异。