Measurement of Physiological pH in Biological Specimens

描述(由申请人提供)：目前常用的酸碱度刻度是为了在参比标准和其他性质类似但酸度不同的介质之间得出酸度函数的准确差异。这些标准是稀缓冲液，通常离子强度接近0.1m；也就是说，比大多数有生理意义的介质(i=0.16m)稀释得多。可以预期对其他类似组成的溶液的结果进行可靠的解释，但其他溶液，如含有较高数量的中性盐的溶液，可能会受到怀疑。尽管已有涵盖大多数生理介质的pH范围的标准可用，但目前很难选择与未知介质的其他性质紧密匹配的参考溶液。对于高于i=0.1m的离子强度，每个人都是“各自为政”，不同实验室之间的结果(单离子活度系数的计算)可能会出现差异。这项研究的一个长期目标是通过使用Pitzer离子相互作用方法消除目前各种惯例(Bates-Guggenheim，i=0.1m以下有效)的限制，以(I)计算在离子强度i=0.16m时确定标准缓冲液的pH值时单个离子物种所需的单一离子活度，类似于在生物样品(血液、血浆等)中发现的那样；(Ii)将它们与基于较简单惯例的那些进行比较；以及(Iii)评估在生理介质(i=0.16m)中标准或感兴趣的介质的中性盐含量的变化所产生的影响。如果成功，应该可以将pH值分配给与生理介质的性质非常匹配的标准参考溶液，从而提高这些介质的实验pH数据的可靠性和意义。在这方面，将研究12种新的生化缓冲化合物(HEPS、AMPSO、HEPPSO、PIPESO、CAPS、CAPS、MOPSO、ACE、CHES、MES、TRICINE和PIPES)。最后，这可能建立一个适用于所有情况(不同离子强度、混合物等)的自洽、统一的pH标度。因此，匹泽公约和提法符合这些要求。在过去，大约有600名学生(现有助学金的大约70名学生)受到了这个机会的挑战，许多人都被激励去从事科学和医学事业。因此，计划将再次向学生提供这个机会，让他们致力于更综合、更有重点和更有价值的研究方案。

DESCRIPTION (provided by applicant): The scale of pH in common use today is designed to yield accurate differences of an acidity function between a standard of reference and other media of a comparable nature but differing acidity. These standards are dilute buffer solutions with typically ionic strengths near 0.1 m; that is, considerably more dilute than most media (I = 0.16 m) of physiological interest. Reliable interpretation of the results for other solutions of comparable composition can be expected, but others, such as those containing higher quantities of neutral salt may be suspect. Although standards covering the range of pH of most physiological media are available, it is presently difficult to choose a reference solution that matches closely in respect to other properties of the unknown media of concern. For ionic strength above I = 0.1 m, everyone is 'on his own' and differences of the results (calculation of the single ion activity coefficient) between various laboratories are likely to occur. A long-term goal of the research is to remove the present restriction of various conventions (the Bates-Guggenheim, valid up to I = 0.1 m) by use of the Pitzer ion-interaction approach to (i) calculate the required single ion activity of a single ionic species in the determination of pH values for the standard buffers at an ionic strength I = 0.16 m, similar to that found in biological specimens (blood, plasma, etc.); to (ii) compare them with those based on the simpler conventions; and to (iii) evaluate the effect produced in physiological media (I = 0.16 m) by variations in the neutral salt content of either the standard or the medium of interest. If successful, the assignment of pH values to standard reference solutions matching closely the properties of physiological media should be possible, with a consequent improvement in the reliability and meaning of experimental pH data for these media. In this connection, twelve new biochemical buffer compounds (HEPPS, AMPSO, HEPPSO, PIPESO, CAPS, CAPSO, MOPSO, ACES, CHES, MES, TRICINE, and PIPES) will be investigated. Finally, this may establish a self-consistent, unified pH scale that is applicable to all cases (different ionic strengths, mixtures, etc.). Thus, the Pitzer convention and formulation fit the bills. In the past, some 600 students (about seventy students for the existing grant) have been challenged by this opportunity and many have been motivated toward careers in science and medicine. Consequently, it is planned that this opportunity will be offered to students once more to work on a more integrated, focused, and meritorious research proposal.